bluuebunny/crossref_metadata_2025 huggingface dataset:
Approximate controllability of non-instantaneous impulsive semilinear measure driven control system with infinite delay via fundamental solution
Authors: Kumar Surendra , Mohammad Abdal Syed
Published: September 2020

This article investigates a new class of non-instantaneous impulsive measure driven control systems with infinite delay. The considered system covers a large class of the hybrid system without any restriction on their Zeno behavior. The concept of measure differential equations is more general as compared to the ordinary impulsive differential equations; consequently, the discussed results are more general than the existing ones. In particular, using the fundamental solution, Krasnoselskii’s fixed-point theorem and the theory of Lebesgue–Stieltjes integral, a new set of sufficient conditions is constructed that ensures the existence of a solution and the approximate controllability of the considered system. Lastly, an example is constructed to demonstrate the effectiveness of obtained results.
Independent Association of Interleukin 6 With Low Dynamic Lung Function and Airflow Limitation in Well-Treated People With Human Immunodeficiency Virus
Authors: Thudium Rebekka F , Knudsen Andreas D , Von Stemann Jakob Hjorth , Hove-Skovsgaard Malene , Hoel Hedda , Mocroft Amanda , Reekie Joanne , Ronit Andreas , Gerstoft Jan , Vestbo Jørgen , Trøseid Marius , Borges Álvaro H , Ostrowski Sisse R , Nielsen Susanne D
Published: September 2020

Background

Human immunodeficiency virus (HIV) infection is associated with an increased risk of chronic pulmonary diseases. We compared cytokine concentrations (interleukin 6 [IL-6], interleukin 1β, 2, 4, 10, and 17A, tumor necrosis factor α, interferon γ, soluble CD14 [sCD14] and soluble CD163 [sCD163]) in people with HIV (PWH) and uninfected controls and investigated whether elevated cytokine concentrations were independently associated with lung function indices in PWH.

Methods

We performed spirometry and measured cytokine concentrations by Luminex immunoassays or enzyme-linked immunoassay in 951 PWH and 79 uninfected controls from the Copenhagen Comorbidity in HIV Infection study. Regression analyses were used to explore associations between elevated cytokine concentrations and lung function indices.

Results

PWH were predominantly male (84.6%) and 94.2% had undetectable viral replication. In PWH, elevated IL-6 was associated with lower forced expiratory volume in 1 second (−212 mL [95% confidence interval, −308 to −116 mL]), lower forced vital capacity (−208 mL [−322 to −93 mL]), and airflow limitation (aOR, 2.62 [1.58–4.36]) (all P < .001) in models adjusted for age, sex, ethnicity, smoking status, body mass index, and CD4 T-cell nadir. The association between IL-6 and dynamic lung function was modified by smoking (P for interaction = .005).

Conclusion

IL-6 levels were elevated and independently associated with low dynamic lung function and airflow limitation in well-treated PWH, suggesting that systemic inflammation may contribute to the pathogenesis of chronic pulmonary diseases.
Reserving Rights: Explaining Human Rights Treaty Reservations
Authors: Zvobgo Kelebogile , Sandholtz Wayne , Mulesky Suzie
Published: September 2020

International relations scholarship has made significant strides in explaining how states design treaty obligations and why they accept treaty commitments. However, far less attention has been paid to factors that may influence states’ modification of their treaty obligations via reservations. We theorize that states will be more likely to enter reservations when treaty obligations increase compliance costs and policy adjustment costs. More specifically, we expect that demanding provisions, i.e., provisions that create strong, precise obligations requiring domestic action, will enhance the likelihood of reservation. To test our theory, we exploit an original dataset that codes reservations at the provision (treaty–article–paragraph) level for the ten core international human rights treaties. Consistent with our expectations, we find that states are more likely to enter reservations on more demanding treaty provisions. In contrast to prior studies, our results indicate that reservations are not driven purely by state-level characteristics such as regime type or the nature of the legal system. Rather, it appears that states weigh individual treaty obligations and calibrate their commitments accordingly.
Identification of a novel tedizolid resistance mutation in rpoB of MRSA after in vitro serial passage
Authors: Shen Tianwei , Penewit Kelsi , Waalkes Adam , Xu Libin , Salipante Stephen J , Nath Abhinav , Werth Brian J
Published: September 2020

Objectives

Tedizolid is an oxazolidinone antimicrobial with activity against Gram-positive bacteria, including MRSA. Tedizolid resistance is uncommon and tedizolid’s capacity to select for cross-resistance to other antimicrobials is incompletely understood. The objective of this study was to further explore the phenotypic and genetic basis of tedizolid resistance in MRSA.

Methods

We selected for tedizolid resistance in an MRSA laboratory strain, N315, by serial passage until an isolate with an MIC ≥1 log2 dilution above the breakpoint for resistance (≥2 mg/L) was recovered. This isolate was subjected to WGS and susceptibility to a panel of related and unrelated antimicrobials was tested in order to determine cross-resistance. Homology modelling was performed to evaluate the potential impact of the mutation on target protein function.

Results

After 10 days of serial passage we recovered a phenotypically stable mutant with a tedizolid MIC of 4 mg/L. WGS revealed only one single nucleotide variant (A1345G) in rpoB, corresponding to amino acid substitution D449N. MICs of linezolid, chloramphenicol, retapamulin and quinupristin/dalfopristin increased by ≥2 log2 dilutions, suggesting the emergence of the so-called ‘PhLOPSa’ resistance phenotype. Susceptibility to other drugs, including rifampicin, was largely unchanged. Homology models revealed that the mutated residue of RNA polymerase would be unlikely to directly affect oxazolidinone action.

Conclusions

To the best of our knowledge, this is the first time that an rpoB mutation has been implicated in resistance to PhLOPSa antimicrobials. The mechanism of resistance remains unclear, but is likely indirect, involving σ-factor binding or other alterations in transcriptional regulation.
Abandoned corrals: colonization and vegetation recovery of ephemeral habitats in silvo-pastoral systems
Authors: Vinograd Arie , Zaady Eli , Kigel Jaime
Published: September 2020

Aims

Management of silvo-pastoral systems in planted and natural forests in semi-arid Mediterranean regions often employs seasonal night corrals for animal protection. This management system changes the spatial distribution of animal excreta, resulting in a net transfer of soil mineral resources and their accumulation in the corrals. After abandonment, corrals are colonized by ruderal species, becoming focal sources for their spread in the forest. We aimed to implement a rational management of seasonal sheep corrals based on a better understanding of the vegetation processes occurring in abandoned corrals, in order to alleviate their negative impact in the forest.

Methods

Relationships between temporal changes in the vegetation, the soil seed-bank and levels of soil nutrients were studied in a chronosequence of abandoned sheep corrals and compared with nearby reference plots in planted Eucalyptus forests grazed by sheep in the semi-arid North-Western Negev, Israel. The region has a bi-seasonal Mediterranean climate, with high dominance of annual species in the grazing range.

Important Findings

Abandoned sheep corrals were colonized by seeds of ruderals originating in older abandoned corrals. Subsequent successional changes occur at a slow rate, driven by the depletion of soil resources in the abandoned corrals, and were still in progress 20 years after abandonment. Ruderals were gradually replaced, first by taller grasses and followed by short grasses, but most forbs and particularly geophytes did not recover during this period. Recovery of the original herbaceous vegetation in the corrals was through seed dispersal from the surrounding vegetation, not from the original soil seed-bank remaining in the corrals after abandonment. Ruderal species in the grazed, planted forests behave as patch-tracking metapopulations. Their persistency depends on constant creation of new corrals compensating for the gradually dwindling populations in older abandoned corrals, and on the availability of dispersal vectors.
Oral colonization by Candida spp. in liver transplant patients: Molecular identification and antifungal susceptibilityOral colonization by Candida spp. in liver transplant
Authors: Sabadin Clarice Elvira Saggin , Lopes Soraia Lima , Gompertz Olga Fischmamm , Santana Gilglécia Novaes Pereira , de Azevedo Melo Analy Salles , Rigo Lilian , Da Matta Daniel Archimedes , Barbosa Dulce Aparecida
Published: September 2020

Candida species are commensal to normal oral microbiota; however, they can cause infections if immune functions are reduced. The aim of this study was to investigate oral colonization, identify species, and test the susceptibility profile to antifungals. A descriptive study included 97 liver transplant patients who attended the transplant center of a referral hospital in southern Brazil. Two oral swab collections were performed, with a 6-month gap between collections. The samples were identified by sequencing the internal transcribed spacer ITS region of the ribosomal DNA. The sensitivity test was performed with fluconazole, amphotericin B, and micafungin using a broth microdilution method recommended by Clinical and Laboratory Standards Institute document M27-A4. Eighty-two patients were investigated and 15 were excluded for presenting clinical infection. The identification of yeasts showed colonization in 66% and 61.9% in collections A and B, respectively. Candida albicans was the most prevalent species in both collections (n = 29/50 and n = 27/49, respectively). In 31 (62%) patients, the yeast species remained the same for 6 months, and in 19 (38%) the colonizing species was substituted. Thirty-two isolates from collection A were sensitive (S) to Fluconazole, 13 sensitive dose-dependent (SDD), and five resistant (R). In collection B, 32 were S, 12 SDD, and 5 R. For amphotericin B and micafungin, all isolates were sensitive. With knowledge of the species and identification of strains resistant to fluconazole, useful information can be alerts about the emergence of antifungal resistance strains.
Clusters have edges: the projected phase-space structure of SDSS redMaPPer clusters
Authors: Tomooka Paxton , Rozo Eduardo , Wagoner Erika L , Aung Han , Nagai Daisuke , Gaines Sasha
Published: September 2020

We study the distribution of line-of-sight velocities of galaxies in the vicinity of Sloan Digital Sky Survey (SDSS) red-sequence Matched-filter Probabilistic Percolation (redMaPPer) galaxy clusters. Based on their velocities, galaxies can be split into two categories: galaxies that are dynamically associated with the cluster, and random line-of-sight projections. Both the fraction of galaxies associated with the galaxy clusters, and the velocity dispersion of the same, exhibit a sharp feature as a function of radius. The feature occurs at a radial scale Redge ≈ 2.2Rλ, where Rλ is the cluster radius assigned by redMaPPer. We refer to Redge as the ‘edge radius’. These results are naturally explained by a model that further splits the galaxies dynamically associated with a galaxy cluster into a component of galaxies orbiting the halo and an infalling galaxy component. The edge radius Redge constitutes a true ‘cluster edge’, in the sense that no orbiting structures exist past this radius. A companion paper tests whether the ‘halo edge’ hypothesis holds when investigating the full three-dimensional phase-space distribution of dark matter substructures in numerical simulations, and demonstrates that this radius coincides with a suitably defined splashback radius.
Extremely precise age and metallicity of the open cluster NGC 2506 using detached eclipsing binaries
Authors: Knudstrup E , Grundahl F , Brogaard K , Slumstrup D , Orosz J A , Sandquist E L , Jessen-Hansen J , Lund M N , Arentoft T , Tronsgaard R , Yong D , Frandsen S , Bruntt H
Published: September 2020

Accurate stellar parameters of stars in open clusters can help constrain models of stellar structure and evolution. Here, we wish to determine the age and metallicity content of the open cluster NGC 2506. To this end, we investigated three detached eclipsing binaries (DEBs; V2032, V4, and V5) for which we determined their masses and radii, as well as four red giant branch stars for which we determined their effective temperatures, surface gravities, and metallicities. Three of the stars in the DEBs have masses close to the cluster turn-off mass, allowing for extremely precise age determination. Comparing the values for the masses and radii of the binaries to BaSTI (a Bag of Stellar Tracks and Isochrones) isochrones, we estimated a cluster age of 2.01 ± 0.10 Gyr. This does depend on the models used in the comparison, where we have found that the inclusion of convective core-overshooting is necessary to properly model the cluster. From red giant branch stars, we determined values for the effective temperatures, the surface gravities, and the metallicities. From these we find a cluster metallicity of −0.36 ± 0.10 dex. Using this value and the values for the effective temperatures, we determine the reddening to be E(b − y) = 0.057 ± 0.004 mag. Furthermore, we derived the distance to the cluster from Gaia parallaxes and found 3.101 ± 0.017 kpc, and we have performed a radial velocity membership determination for stars in the field of the cluster. Finally, we report on the detection of oscillation signals in γ Dor and δ Scuti members in data from the Transiting Exoplanet Survey Satellite (TESS) mission, including the possible detection of solar-like oscillations in two of the red giants.
Variable stars in the field of intermediate-age open cluster NGC 559
Authors: Joshi Y C , John Ancy A , Maurya J , Panchal A , Kumar Brijesh , Joshi Santosh
Published: September 2020

This work presents the first long-term photometric variability survey of the intermediate-age open cluster NGC 559. Time series V-band photometric observations on 40 nights taken over more than 3 yr with three different telescopes are analysed to search for variable stars in the cluster. We investigate the data for the periodicity analysis and reveal 70 variable stars including 67 periodic variables in the target field, all of them are newly discovered. The membership analysis of the periodic variables reveals that 30 of them belong to the cluster and remaining 37 are identified as field variables. Out of the 67 periodic variables, 48 are short-period (P < 1 d) variables and 19 are long-period (P > 1 d) variables. The variable stars have periodicity between 3 h to 41 d and their brightness ranges from V  = 10.9 to 19.3 mag. The periodic variables belonging to the cluster are then classified into different variability types on the basis of observational properties such as shape of the light curves, periods, amplitudes, as well as their positions in the Hertzsprung–Russell (H–R) diagram. As a result, we identify 1 Algol type eclipsing binary, 1 possible blue straggler star, 3 slowly pulsating B type stars, 5 rotational variables, 11 non-pulsating variables, 2 FKCOM variables, and remaining 7 are characterized as miscellaneous variables. We also identify three eclipsing binary stars (EBs) belonging to the field star population. The phoebe package is used to analyse the light curve of all four EBs in order to determine the parameters of the binary systems such as masses, temperatures, and radii.
Galaxy and mass assembly: luminosity and stellar mass functions in GAMA groups
Authors: Vázquez-Mata J A , Loveday J , Riggs S D , Baldry I K , Davies L J M , Robotham A S G , Holwerda B W , Brown M J I , Cluver M E , Wang L , Alpaslan M , Bland-Hawthorn J , Brough S , Driver S P , Hopkins A M , Taylor E N , Wright A H
Published: September 2020

How do galaxy properties (such as stellar mass, luminosity, star formation rate, and morphology) and their evolution depend on the mass of their host dark matter halo? Using the Galaxy and Mass Assembly group catalogue, we address this question by exploring the dependence on host halo mass of the luminosity function (LF) and stellar mass function (SMF) for grouped galaxies subdivided by colour, morphology, and central/satellite. We find that spheroidal galaxies in particular dominate the bright and massive ends of the LF and SMF, respectively. More massive haloes host more massive and more luminous central galaxies. The satellites LF and SMF, respectively, show a systematic brightening of characteristic magnitude, and increase in characteristic mass, with increasing halo mass. In contrast to some previous results, the faint-end and low-mass slopes show little systematic dependence on halo mass. Semi-analytic models and simulations show similar or enhanced dependence of central mass and luminosity on halo mass. Faint and low-mass simulated satellite galaxies are remarkably independent of halo mass, but the most massive satellites are more common in more massive groups. In the first investigation of low-redshift LF and SMF evolution in group environments, we find that the red/blue ratio of galaxies in groups has increased since redshift z ≈ 0.3 relative to the field population. This observation strongly suggests that quenching of star formation in galaxies as they are accreted into galaxy groups is a significant and ongoing process.
Patterns of ‘Disorder’ During the 2019 Protests in Hong Kong: Policing, Social Identity, Intergroup Dynamics, and Radicalization
Authors: Stott Clifford , Ho Lawrence , Radburn Matt , Chan Ying Tung , Kyprianides Arabella , Morales Patricio Saavedra
Published: September 2020

Across the latter half of 2019, Hong Kong became the focus of world attention as it was rocked by a wave of increasingly violent confrontations between police and protesters. Both inside and outside the Territory, several powerful political actors have argued that the paramilitary-style police interventions used to manage the protests were necessary because the disorder was being fermented by agitators. In contrast, this article explores the utility of the Elaborated Social Identity Model of crowd behaviour to help explore and explain some of the social psychological dynamics through which the 2019 protests became ‘radicalised’. The article explores three key phases of their evolution to draw out the patterns of collective action and variations in policing approaches. We show that early demonstrations were focused predominantly on preventing the implementation of controversial legislation but spread and changed in form as a function of the use of crowd dispersal tactics by police. Moreover, we show how police inaction at other critical moments helped amplify perceptions of police illegitimacy that further radicalized protesters. Drawing upon a body of primary interview and secondary survey data, we also provide a social psychological analysis. We argue the observed patterns of collective action were underpinned by identity change and empowerment processes brought about as a consequence of both the structural context and the intergroup dynamics created in part by coercive policing practices.
BDNF and JNK Signaling Modulate Cortical Interneuron and Perineuronal Net Development: Implications for Schizophrenia-Linked 16p11.2 Duplication Syndrome
Authors: Willis Ashleigh , Pratt Judith A , Morris Brian J
Published: September 2020

Schizophrenia (SZ) is a neurodevelopmental disorder caused by the interaction of genetic and environmental risk factors. One of the strongest genetic risk variants is duplication (DUP) of chr.16p11.2. SZ is characterized by cortical gamma-amino-butyric acid (GABA)ergic interneuron dysfunction and disruption to surrounding extracellular matrix structures, perineuronal nets (PNNs). Developmental maturation of GABAergic interneurons, and also the resulting closure of the critical period of cortical plasticity, is regulated by brain-derived neurotrophic factor (BDNF), although the mechanisms involved are unknown. Here, we show that BDNF promotes GABAergic interneuron and PNN maturation through JNK signaling. In mice reproducing the 16p11.2 DUP, where the JNK upstream activator Taok2 is overexpressed, we find that JNK is overactive and there are developmental abnormalities in PNNs, which persist into adulthood. Prefrontal cortex parvalbumin (PVB) expression is reduced, while PNN intensity is increased. Additionally, we report a unique role for TAOK2 signaling in the regulation of PVB interneurons. Our work implicates TAOK2-JNK signaling in cortical interneuron and PNN development, and in the responses to BDNF. It also demonstrates that over-activation of this pathway in conditions associated with SZ risk causes long-lasting disruption in cortical interneurons.
Inhibition by Imipramine of the Voltage-Dependent K+ Channel in Rabbit Coronary Arterial Smooth Muscle Cells
Authors: An Jin Ryeol , Seo Mi Seon , Jung Hee Seok , Heo Ryeon , Kang Minji , Han Eun-Taek , Park Hongzoo , Jung Won-Kyo , Choi Il-Whan , Park Won Sun
Published: September 2020

Imipramine, a tricyclic antidepressant, is used in the treatment of depressive disorders. However, the effect of imipramine on vascular ion channels is unclear. Therefore, using a patch-clamp technique we examined the effect of imipramine on voltage-dependent K+ (Kv) channels in freshly isolated rabbit coronary arterial smooth muscle cells. Kv channels were inhibited by imipramine in a concentration-dependent manner, with an IC50 value of 5.55 ± 1.24 µM and a Hill coefficient of 0.73 ± 0.1. Application of imipramine shifted the steady-state activation curve in the positive direction, indicating that imipramine-induced inhibition of Kv channels was mediated by influencing the voltage sensors of the channels. The recovery time constants from Kv-channel inactivation were increased in the presence of imipramine. Furthermore, the application of train pulses (of 1 or 2 Hz) progressively augmented the imipramine-induced inhibition of Kv channels, suggesting that the inhibitory effect of imipramine is use (state) dependent. The magnitude of Kv current inhibition by imipramine was similar during the first, second, and third depolarizing pulses. These results indicate that imipramine-induced inhibition of Kv channels mainly occurs in the closed state. The imipramine-mediated inhibition of Kv channels was associated with the Kv1.5 channel, not the Kv2.1 or Kv7 channel. Inhibition of Kv channels by imipramine caused vasoconstriction. From these results, we conclude that imipramine inhibits vascular Kv channels in a concentration- and use (closed-state)-dependent manner by changing their gating properties regardless of its own function.
Postcranial skeletal development of Mugil cephalus (Teleostei: Mugiliformes): morphological and life-history implications for Mugiliformes
Authors: Thieme Philipp , Vallainc Dario , Moritz Timo
Published: September 2020

Within the fish taxon Mugiliformes, the larval development of Mugil cephalus has been studied most intensively, because it has the widest range of distribution among all mugilids and is of interest to aquaculture all over the world. Although numerous studies have dealt with larval rearing, growth and development, the osteological development of M. cephalus and mugiliforms in general has largely been neglected. Herein, we describe the skeletal development of mullets for the first time. Cleared and double-stained specimens of aquaculture-reared M. cephalus and wild-caught mugilid larvae were examined to describe the early development of the pectoral and pelvic girdle, the vertebral column and the caudal and median fins. The description of four embryonic and six larval developmental steps within the embryonic and larval period enables us to compare larval sizes of reared and wild-caught larvae. Ontogenetic fusions of ural centra 1 and 2 into a compound centrum, in addition to the fusion of two pterygiophores in the anal fin, have implications for the perception of the adult morphology. Moreover, comparison of mugilid development with that of other ovalentarian taxa shows that recent phylogenetic hypotheses need further morphological investigation.
Adenotonsillectomy as a treatment for sleep-disordered breathing in children with ADHD
Authors: Perez Alexandra , Hunter Kimberly
Published: September 2020

Sleep-disordered breathing (SDB) and attention deficit hyperactivity disorder (ADHD) are common disorders diagnosed in children. Although these diagnoses were previously considered unrelated, research now is showing that some symptoms of ADHD, specifically oppositional behavior, hyperactivity, and impulsivity, can be related to SDB in children and differs from bona fide ADHD. This article explores the connection between the two disorders and the importance of identifying and screening for SDB in children presenting with similar symptoms related to ADHD. The article also examines symptom improvement in patients with ADHD symptoms after an adenotonsillectomy, one of the first-line treatments for children diagnosed with SDB; this procedure may reduce the need for long-term stimulant use in some children with ADHD.
Understanding the most commonly billed diagnoses in primary care
Authors: Rogers Julia , Spain Scarlet
Published: September 2020

This article, part of a series about the most commonly billed diagnoses in primary care, describes the pathophysiologic processes of the three most common types of headache disorders as well as how the clinical manifestations and treatments are linked to the pathogenesis of the disorders.
Prognostic Value of Hypochloremia in Critically Ill Patients With Decompensated Cirrhosis
Authors: Sumarsono Andrew , Wang Jiexin , Xie Luyu , Chiang Giuliana Cerro , Tielleman Thomas , Messiah Sarah E. , Singal Amit G. , Mufti Arjmand , Chen Catherine , Leveno Matthew
Published: September 2020

Objectives:

Cirrhosis is frequently complicated by electrolyte disturbances, with prior studies primarily focused on the importance of hyponatremia. Emerging evidence on patients with chronic heart failure and chronic kidney disease has identified hypochloremia as an independent predictor for mortality. This study aimed to investigate the prognostic value of serum chloride and its association with mortality in cirrhotic patients.

Design:

Retrospective cohort study.

Setting:

The medical ICU at Parkland Memorial Hospital, a tertiary care public health system in Dallas, Texas.

Patients:

Adult patients with confirmed diagnosis of decompensated cirrhosis who were admitted to the ICU between March 2015 and March 2017.

Interventions:

None.

Measurements and Main Results:

Kaplan-Meier analysis and multivariable Cox proportional hazard ratio models were performed to determine the impact of hypochloremia on 180-day mortality. Of the 389 enrolled patients, 133 (34.2%) died within 180 days of ICU admission. Patients with hypochloremia had higher 180-day mortality than those with normochloremia (45.2% vs 26.7%; p < 0.0001). Cumulative survival via the Kaplan-Meier method was significantly lower in the hypochloremic group. Serum chloride was independently associated with 180-day mortality with multivariable adjustment (hazard ratio, 0.95; 95% CI, 0.93–0.98; p = 0.001) or after adjusting for Model for End-stage Liver Disease or Sequential Organ Failure Assessment. Contrarily, the inverse association between serum sodium and mortality no longer existed in all multivariable models.

Conclusions:

Serum chloride is independently and inversely associated with short-term mortality in critically ill cirrhotic patients. Hypochloremia, but not hyponatremia, remained associated with mortality with multivariable analyses, suggesting that hypochloremia may account for the mortality risk previously attributed to hyponatremia. These findings signify the prognostic value of serum chloride and potential inclusion of chloride into future cirrhosis prognostic scores.
Thrombotic Complications of COVID-19 Infection
Authors: Castro Rebecca A. , Frishman William H.
Published: September 2020

The novel coronavirus (severe acute respiratory syndrome CoV-2 [SARS-CoV-2]), also known as COVID-19, is a single-stranded enveloped RNA virus that created a Public Health Emergency of International Concern in January 2020, with a global case burden of over 15 million in just 7 months. Infected patients develop a wide range of clinical manifestations—typically presenting with fever, cough, myalgia, and fatigue. Severely ill patients may fall victim to acute respiratory distress syndrome, acute heart injuries, neurological manifestations, or complications due to secondary infections. These critically ill patients are also found to have disrupted coagulation function, predisposing them to consumptive coagulopathies, and both venous and thromboembolic complications. Common laboratory findings include thrombocytopenia, elevated D-dimer, fibrin degradation products, and fibrinogen, all of which have been associated with greater disease severity. Many cases of pulmonary embolism have been noted, along with deep vein thrombosis, ischemic stroke, myocardial infarction, and systemic arterial embolism. The pathogenesis of coronavirus has not been completely elucidated, but the virus is known to cause excessive inflammation, endothelial injury, hypoxia, and disseminated intravascular coagulation, all of which contribute to thrombosis formation. These patients are also faced with prolonged immobilization while staying in the hospital or intensive care unit. It is important to have a high degree of suspicion for thrombotic complications as patients may rapidly deteriorate in severe cases. Evidence suggests that prophylaxis with anticoagulation may lead to a lower risk of mortality, although it does not eliminate the possibility. The risks and benefits of anticoagulation treatment should be considered in each case. Patients should be regularly evaluated for bleeding risks and thrombotic complications.
Evaluation of Plasma Biomarker Utility for the Gastrointestinal Acute Radiation Syndrome in Non-human Primates after Partial Body Irradiation with Minimal Bone Marrow Sparing through Correlation with Tissue and Histological Analyses
Authors: Kumar Praveen , Wang Pengcheng , Tudor Gregory , Booth Catherine , Farese Ann M. , MacVittie Thomas J. , Kane Maureen A.
Published: September 2020

Exposure to total- and partial-body irradiation following a nuclear or radiological incident result in the potentially lethal acute radiation syndromes of the gastrointestinal and hematopoietic systems in a dose- and time-dependent manner. Radiation-induced damage to the gastrointestinal tract is observed within days to weeks post-irradiation. Our objective in this study was to evaluate plasma biomarker utility for the gastrointestinal acute radiation syndrome in non-human primates after partial body irradiation with minimal bone marrow sparing through correlation with tissue and histological analyses. Plasma and jejunum samples from non-human primates exposed to partial body irradiation of 12 Gy with bone marrow sparing of 2.5% were evaluated at various time points from day 0 to day 21 as part of a natural history study. Additionally, longitudinal plasma samples from non-human primates exposed to 10 Gy partial body irradiation with 2.5% bone marrow sparing were evaluated at timepoints out to 180 d post-irradiation. Plasma and jejunum metabolites were quantified via liquid chromatography–tandem mass spectrometry and histological analysis consisted of corrected crypt number, an established metric to assess radiation-induced gastrointestinal damage. A positive correlation of metabolite levels in jejunum and plasma was observed for citrulline, serotonin, acylcarnitine, and multiple species of phosphatidylcholines. Citrulline levels also correlated with injury and regeneration of crypts in the small intestine. These results expand the characterization of the natural history of gastrointestinal acute radiation syndrome in non-human primates exposed to partial body irradiation with minimal bone marrow sparing and also provide additional data toward the correlation of citrulline with histological endpoints.
Case Report: Suspected Donor Transmission of Acanthamoeba Keratitis After Deep Anterior Lamellar Keratoplasty
Authors: Ward Matthew S. , Bontu Sneha , Martheswaran Tanisha , Mamalis Nick , Moshirfar Majid
Published: September 2020

Purpose:

In our report, we present a suspected case of donor-derivedAcanthamoebakeratitis after deep anterior lamellar keratoplasty. To the authors' knowledge, there have been no confirmed cases ofAcanthamoebakeratitis transmission through corneal transplantation.

Methods:

Deep anterior lamellar keratoplasty was performed on the right eye of a 33-year-old man with severe bilateral keratoconus and an intolerance to all forms of contact lenses. The postoperative visual acuity deteriorated, while inflammation, rising ocular pressure, increasing corneal thickness, and severe eye pain began to present. Confocal imaging revealed hyperreflective cysts and trophozoite figures representative of amoebic keratitis. Despite an additional penetrating keratoplasty, antiamoeba therapy, and corneal crosslinking, the patient's condition worsened, resulting in stromal melt and corneal perforation. Emergent combined surgery of temporary keratoprosthesis, vitrectomy, lensectomy, and iridectomy was performed, along with Ahmed valve shunt placement and another penetrating keratoplasty.

Results:

The infection was resistant to aggressive antiamoeba therapy, but after the emergent combined surgery, the graft re-epithelialized quickly and has since remained clear, with no presence of keratitis.

Conclusions:

Several signs led us to believe that this case was donor-derived. There was little opportunity for graft exposure to the amoeba, and deep amoebic cysts and trophozoites were present on postoperative week 1—a highly unusual time course and depth of invasion for primary amoebic infection. In addition, pathological analysis revealed cysts only within the confines of the donor tissue and none in the recipient;Acanthamoebacysts would have been present in the recipient rim tissue if the infection originated from the patient himself.
Comprehensive Detection of Candidate Pathogens in the Lower Respiratory Tract of Pediatric Patients With Unexpected Cardiopulmonary Deterioration Using Next-Generation Sequencing
Authors: Takeuchi Suguru , Kawada Jun-ichi , Horiba Kazuhiro , Yamaguchi Makoto , Okumura Toshihiko , Suzuki Takako , Torii Yuka , Kawabe Shinji , Wada Sho , Ikeyama Takanari , Ito Yoshinori
Published: September 2020

Objectives:

Next-generation sequencing has been applied to the investigation of microorganisms in several clinical settings. We investigated the infectious etiologies in respiratory specimens from pediatric patients with unexpected cardiopulmonary deterioration using next-generation sequencing.

Design:

Retrospective, single-center, observational study.

Setting:

Tertiary care, a children’s hospital.

Subjects:

The study enrolled a total of 16 pediatric patients with unexpected cardiopulmonary deterioration who were admitted to the PICU. Ten bronchoalveolar lavage fluid and six transtracheal aspirate samples were analyzed.

Interventions:

None.

Measurements and Main Results:

RNA libraries were prepared from specimens and analyzed using next-generation sequencing. One or more bacterial/viral pathogens were detected in the bronchoalveolar lavage fluid or transtracheal aspirate specimens from 10 patients. Bacterial and viral coinfection was considered in four cases. Compared with the conventional culture and viral antigen test results, an additional six bacterial and four viral pathogens were identified by next-generation sequencing. Conversely, among 18 pathogens identified by the conventional methods, nine pathogens were detected by next-generation sequencing. Candidate pathogens (e.g., coxsackievirus A6 and Chlamydia trachomatis) were detected by next-generation sequencing in four of 10 patients in whom no causative pathogen had been identified by conventional methods.

Conclusions:

Our results suggest that viral and bacterial infections are common triggers in unexpected cardiopulmonary deterioration in pediatric patients. Next-generation sequencing has the potential to contribute to clarification of the etiology of pediatric critical illness.
How Age Matters in the Assessment of Vertigo in the Pediatric Emergency Department
Authors: Grasso Antonio , Poropat Federico , Kamagni Vodié Theodora , Ghirardo Sergio , Barbi Egidio
Published: September 2020

Vertigo is a relatively frequent cause for referral to the pediatric emergency department, and it is usually caused by benign or self-limiting etiology. However, it could be difficult to evaluate especially in the younger child and could also conceal serious illness as encephalitis or cerebellitis. Our survey collected in a 10-year period 757 children assessed in pediatric emergency department for vertigo and stratified this population for etiology and for group of age: younger than 6 years (113, 14.9%), between 7 and 12 years (251, 33.2%), and older than 12 years (393, 51.9%). In addition, associated signs and symptoms, evaluation by a neurologist or an otorhinolaryngologist, and instrumental investigations were recorded.

We found that age is the most important variable to assess the possibility of a central nervous system disease as etiology cause of vertigo with a significant difference of incidence between the younger group (younger than 6 years, 23%) and older groups (3% and 1%; P < 0.001).

This finding should reinforce the index of suspicion for a central nervous system illness as cause of vertigo in the preschool children with an accurate workup including evaluation by a neurologist or an otorhinolaryngologist and instrumental investigations as needed.
Two-Year-Old With Sleep Disturbance and Left Arm Movements
Authors: Sierakowski James , Koul Pulin
Published: September 2020

A 29-month-old boy presented to a pediatric emergency department with complaints of trouble sleeping for more than a week. History consisted of episodes of screaming while asleep from which he could not be awakened. A detailed physical examination revealed left arm dystonia and left plantar reflex to be upgoing. Upon admission, all imaging and an electroencephalogram were normal. Extensive laboratory work was done showing positive anti-N-methyl-D-Aspartate (NMDA) antibody in the cerebrospinal fluid. Inpatient care included intravenous immunoglobulin (IVIG) and Solumedrol. Cellcept was started after definitive diagnosis and continued on discharge. The patient was discharged with residual defects that will need long-term therapy. The varied presenting symptoms are easily misinterpreted as common clinical entities. Pediatric emergency physicians need to be aware of the wide spectrum of presenting symptoms for this clinical entity because earlier diagnosis and treatment have been shown to improve long-term morbidity.
Customized Surgical Protocols for Guided Bone Regeneration Using 3D Printing Technology: A Retrospective Clinical Trial
Authors: Manzano Romero Paloma , Vellone Valentino , Maffia Francesco , Cicero Giuseppe
Published: September 2020

3D printing is one of the most significant technological advancements of the modern era. Among the various surgical disciplines, this new technology has shown significant improvements in the diagnosis and treatment of many diseases. The application of 3D printing has many benefits in training, preoperative planning and education.

A retrospective study was conducted at the European University of Madrid (UEM). Patients were selected in this study using the following inclusion criteria: age over 18 years old, a preoperative cone beam computed tomography (CBCT), patients with moderate or severe vertical or horizontal defects, presence or absence of the tooth in the area to regenerate, no bone regeneration surgery before. Bone defects were measured: in the CBCT using White Fox Imaging, on the 3D printed model and then intraoperatively from the area to be regenerated. The average of the bone defects on the 3D measurements was statistically compared with the average of the bone defect measurements in the patient's mouth to evaluate the model reliability.

The mean age of the patients was 53,07 years old, with a range from 45 to 63. Females were more affected than males, with a ratio of 12/13 (92%). The most frequent side affected was maxilla 10/13 (77%) and the most type of defect reported was horizontal 10/13 (77%). The means in width (x = 8,2923) and height (x = 6,9615) of the 3D model, were close and clinically acceptable if compared with the means obtained from the measurements in width (x = 7,9230) and height (x = 6,8076) of the patients’ bone defects. None of the patients underwent further surgeries or needed intraoperative surgical corrections obtaining reliable results in terms of presurgical planning.

It is possible to affirm that the use of 3D printed models can be a crucial complement when planning guided bone regeneration procedures, due to high reliability, and representing a turning point in many aspects of oral surgery.
A SARS-CoV-2 Reference Standard Quantified by Multi-digital PCR Platforms for Quality Assessment of Molecular Tests
Authors: Zhou Haiwei , Liu Donglai , Ma Liang , Ma Tingting , Xu Tingying , Ren Lili , Li Liang , Xu Sihong
Published: September 2020

SARS-CoV-2 is the seventh coronavirus known to infect humans and has caused an emerging and rapidly evolving global pandemic (COVID-19) with significant morbidity and mortality. To meet the urgent and massive demand for the screening and diagnosis of infected individuals, many in vitro diagnostic assays using nucleic acid tests (NATs) have been urgently authorized by regulators worldwide. The limit of detection (LoD) is a crucial feature for a diagnostic assay to detect SARS-CoV-2 in clinical samples, and a reference standard with a well-characterized concentration or titer is of the utmost importance for LoD studies. Although several reference standards of plasmids or synthetic RNA carrying specific genomic regions of SARS-CoV-2 have already been announced, a reference standard for inactivated virus particles with accurate concentration is still needed to evaluate the complete procedure including nucleic acid extraction and to accommodate customized primer-probe sets targeting different genome sequences. Here, we performed a collaborative study to estimate the NAT-detectable units as viral genomic equivalent quantity (GEQ) of an inactivated whole-virus SARS-CoV-2 reference standard candidate using digital PCR (dPCR) on multiple commercialized platforms. The median of the quantification results (4.6×105 ± 6.5×104 GEQ/mL) was treated as the consensus true value of GEQ of virus particles in the reference standard. This reference standard was then used to challenge the LoDs of six officially approved diagnostic assays. Our study demonstrates that an inactivated whole virus quantified by dPCR can serve as a reference standard and provides a unified solution for assay development, quality control, and regulatory surveillance.
Pentoxifylline and Covid-19: A Systematic Review
Authors: Ramonfaur Diego , González-Assad Carlos A. , Paredes-Vázquez José G.
Published: September 2020

At more than 10 months after the first case of COVID-19 was documented, the understanding of the pathogenesis of this viral illness is growing on a daily basis. A massive pro-inflammatory response on infected individuals involving several cytokines seems to play a key role on disease. As a result, therapeutic efforts have focused on anti-inflammatory strategies to ameliorate the disease, in sight of a lack of a truly effective anti-viral agent. Pentoxifylline (PTX) has been proposed by multiple authors as a potential therapeutic ally, targeting a variety of mechanisms as it has been shown to have antiviral, anti-inflammatory and hemodynamic effects. Importantly, anti-inflammatory effects center on down-regulation of cytokines such as interleukins and tumor necrosis factor. In pre-pandemic studies, PTX has demonstrated to change the clinical course of inflammatory diseases such as acute respiratory distress syndrome, which is a hallmark of severe COVID-19. Researchers agree it is pertinent to experimentally evaluate the effect this drug has on COVID-19 patients. The objective of this review is to summarize all the proposed mechanisms by which PTX may aid in the treatment of COVID-19, as well as prevent its deadly complications. Our interpretation of the literature is that the benefits PTX may bring to a patient with COVID-19 outweigh the risks this drug might pose on them. As a result, there is consensus regarding the evaluation of PTX in further experimental studies to better characterize its effects on COVID-19 patients.
Non-stationary Spatio-Temporal Modeling of COVID-19 Progression in The U.S.
Authors: Bai Yue , Safikhani Abolfazl , Michailidis George
Published: September 2020

The fast transmission rate of COVID-19 worldwide has made this virus the most important challenge of year 2020. Many mitigation policies have been imposed by the governments at different regional levels (country, state, county, and city) to stop the spread of this virus. Quantifying the effect of such mitigation strategies on the transmission and recovery rates, and predicting the rate of new daily cases are two crucial tasks. In this paper, we propose a modeling framework which not only accounts for such policies but also utilizes the spatial and temporal information to characterize the pattern of COVID-19 progression. Specifically, a piecewise susceptible-infected-recovered (SIR) model is developed while the dates at which the transmission/recover rates change significantly are defined as “break points” in this model. A novel and data-driven algorithm is designed to locate the break points using ideas from fused lasso and thresholding. In order to enhance the forecasting power and to describe additional temporal dependence among the daily number of cases, this model is further coupled with spatial smoothing covariates and vector auto-regressive (VAR) model. The proposed model is applied to several U.S. states and counties, and the results confirm the effect of “stay-at-home orders” and some states’ early “re-openings” by detecting break points close to such events. Further, the model performed satisfactorily short-term forecasts of the number of new daily cases at regional levels by utilizing the estimated spatio-temporal covariance structures. Finally, some theoretical results and empirical performance of the proposed methodology on synthetic data are reported which justify the good performance of the proposed method.
Communicating the health risks of wildfire smoke exposure: Health literacy considerations of public health campaigns
Authors: Cook Lily A.
Published: September 2020

Effective communication about the health effects of wildfire smoke is important to protect the public, especially those most vulnerable to the effects of exposure: people with chronic respiratory conditions, children, and older adults. The objective of this paper is to examine the clarity and accessibility of materials intended to provide education about the health effects of wildfire. The Centers for Disease Control’s Clear Communications Index (CCI) is used to evaluate whether materials adhere to the main principles of health literacy: clarity and accessibility. This analysis found that only 32% of the materials received a passing score on the Clear Communications Index. Most materials were successful at clearly presenting specific behavioral recommendations, particularly that people should avoid exposure to air polluted by wildfire smoke by staying indoors, reducing activity levels, and using air purifiers or approved dust masks. However, materials often failed to acknowledge any uncertainty around these recommendations. Creators of these materials may want to incorporate more relevant illustrations to support the main message, and consider how information about the risks and benefits of the recommended behaviors can most clearly be presented.