Search

Background: Plasmodium falciparum malaria is still a leading cause of child mortality in sub-Saharan Africa. The clinical manifestations of malaria range from asymptomatic infection to severe disease. The variation in clinical presentation is partly attributed to host genetic factors with estimated narrow-sense heritability of 23%. Here, we investigate the associations between candidate gene polymorphisms and the likelihood of severe malaria (SM) in a cohort of Malian children. Methods: Based on our previous genome-wide association studies (GWAS) analysis, candidate genes were selected for in-depth analysis using several criteria including gene-level GWAS scores, functional overlap with malaria pathogenesis, and evidence of association with protection or susceptibility to other infectious or inflammatory diseases. Single Nucleotide Polymorphisms (SNPs) residing within these genes were selected mainly based on p-values from previous severe malaria susceptibility GWAS studies and minor allele frequency (MAF) in West African populations. Results: Of 182 candidate genes reported in our previous study, 11 genes and 22 SNPs residing in these genes were selected. The selected SNPs were genotyped using KASP technology in 477 DNA samples (87 SM and 390 controls). Logistic regression analysis revealed that a common intron variant, rs13340578 in CUB and Sushi Multi Domain (CSMD1) gene, is associated with increased odds of SM in recessive mode of inheritance (MAF = 0.42, OR = 1.8, 95% CI = [1.78, 1.84], p = 0.029). The SNP is in linkage disequilibrium (LD) with multiple variants with regulatory features. Conclusion: Taken together, the current study showed that an intron variant rs13340578, residing in CSMD1 gene, is associated with increased susceptibility to malaria. This finding suggests that modified regulation of complement may contribute to malaria disease severity. Further studies are needed to identify the causal variants and the underlying molecular mechanisms. [ABSTRACT FROM AUTHOR]

Long baseline bistatic radar systems herald enhanced sensitivity and metric accuracy for space objects in geosynchronous orbits and beyond. Radio telescopes are ideal participants in such a system; in particular, they often feature large apertures with low‐noise temperatures and have stable, synchronised clocks. Pairing radio telescopes with high‐power radars creates new methodologies for Space Domain Awareness. This paper describes long baseline bistatic measurements using the Millstone Hill Radar in the USA, the Tracking and Imaging Radar in Germany, multiple receivers of the enhanced multi‐element remotely linked interferometer network array in the United Kingdom, and the Westerbork Synthesis Radio Telescope in the Netherlands. The authors, a Research Task Group formed by the NATO Science and Technology Organisation Sensors and Electronic Technology Panel (SET‐293), performed novel bistatic and monostatic radar imaging experiments with real on‐orbit tumbling rocket bodies. These experiments on tumbling objects at near‐geosynchronous orbits highlight successful demonstrations of advanced bistatic Doppler characterisation across diverse imaging geometries. Specialised Doppler processing on tumbling targets, such as the Doppler superpulse algorithm, enables high‐fidelity rotation period estimation and determination of minimum target size. [ABSTRACT FROM AUTHOR]

Objectives: The paralaryngeal muscles are thought to be hyperfunctional with phonation in patients with primary muscle tension dysphonia (pMTD). However, objective, quantitative tools to assess paralaryngeal movement patterns lack. The objectives of this study were to (1) validate the use of optical flow to characterize paralaryngeal movement patterns with phonation, (2) characterize phonatory optical flow velocities and variability of the paralaryngeal muscles before and after a vocal load challenge, and (3) compare phonatory optical flow measures to standard laryngoscopic, acoustic, and self‐perceptual assessments. Methods: Phonatory movement velocities and variability of the paralaryngeal muscles at vocal onsets and offsets were quantified from ultrasound videos and optical flow methods across 42 subjects with and without a diagnosis of pMTD, before and after a vocal load challenge. Severity of laryngoscopic mediolateral supraglottic compression, acoustic perturbation, and ratings of vocal effort and discomfort were also obtained at both time points. Results: There were no significant differences in optical flow measures of the paralaryngeal muscles with phonation between patients with pMTD and controls. Patients with pMTD had significantly more supraglottic compression, higher acoustic perturbations, and higher vocal effort and vocal tract discomfort ratings. Vocal load had a significant effect on vocal effort and discomfort but not on supraglottic compression, acoustics, or optical flow measures of the paralaryngeal muscles. Conclusion: Optical flow methods can be used to study paralaryngeal muscle movement velocity and variability patterns during vocal productions, although the role of the paralaryngeal in pMTD diagnostics (e.g., vocal hyperfunction) remains suspect. Level of Evidence: 2 Laryngoscope, 134:1792–1801, 2024 [ABSTRACT FROM AUTHOR]

Placental accumulation of Plasmodium falciparum infected erythrocytes results in maternal anemia, low birth weight, and pregnancy loss. The parasite protein VAR2CSA facilitates the accumulation of infected erythrocytes in the placenta through interaction with the host receptor chondroitin sulfate A (CSA). Antibodies that prevent the VAR2CSA-CSA interaction correlate with protection from placental malaria, and VAR2CSA is a high-priority placental malaria vaccine antigen. Here, structure-guided design leveraging the full-length structures of VAR2CSA produced a stable immunogen that retains the critical conserved functional elements of VAR2CSA. The design expressed with a six-fold greater yield than the full-length protein and elicited antibodies that prevent adhesion of infected erythrocytes to CSA. The reduced size and adaptability of the designed immunogen enable efficient production of multiple variants of VAR2CSA for use in a cocktail vaccination strategy to increase the breadth of protection. These designs form strong foundations for the development of potent broadly protective placental malaria vaccines. Author summary: Malaria remains a major cause of death globally despite considerable dedication to eradication. Plasmodium falciparum is the most lethal malaria parasite that infects human. One reason for the parasite's deadly impact lies in the expression of the Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) protein family. These proteins adhere to host receptors leading to parasite accumulation in various tissues and organs. VAR2CSA is a PfEMP1 protein that binds to a host receptor in the placenta causing severe outcomes for pregnant women and their unborn children including maternal anemia, low birth weight, still birth, and loss of pregnancy. The development of a vaccine to combat these devastating outcomes has long been anticipated, but the intricate and diverse nature of VAR2CSA has posed significant hurdles. Here, we adopted structure-guided principles to design a next-generation VAR2CSA vaccine candidate, HPISVpmv1, that is stable, has high production yields, and consists of the entire functional domains of VAR2CSA. Preclinical studies showed that HPISVpmv1 is immunogenic and effective, and the adoption of a cocktail immunization strategy produced antibodies that worked against multiple strains. This work provides new insights into vaccine development for malaria and other highly variable human pathogens. [ABSTRACT FROM AUTHOR]

Background: Altered Airway Anatomy (AAA), including tracheostomies and laryngectomies, may represent an area of unease for non-Otolaryngology trainees, due to a lack of exposure, structured education, or dedicated training in altered airway management. Inability to effectively stabilize an altered airway is associated with significant risk of patient morbidity and mortality. This study aims to assess the efficacy of a concise curriculum using three-dimensional (3D) printed airway models for skill training in improving Anesthesiology trainees' competency in AAA management. Methods: A prospective cohort of 42 anesthesiology residents at a tertiary care institution were guided through a 75-min curriculum on AAA, including case discussion, surgical video, and hands-on practice with tracheostomy and laryngectomy skills trainers. Pre- and post- course surveys assessing provider confidence (Likert scale) and knowledge (multiple choice questions) were administered. Additionally, an observed skills competency assessment was performed. Results: Self-perceived confidence improved from a summative score across all domains of 23.65/40 pre-course to 36.39/40 post-course (n = 31, p < 0.001). Technical knowledge on multiple choice questions improved from 71 to 95% (n = 29, p < 0.001). In the completed skills competency assessment, 42/42 residents completed 5/5 assessed tasks successfully, demonstrating objective skills-based competency. Conclusions: This study demonstrates an improvement in anesthesiology resident self-assessed confidence, objective knowledge, and skills based competency surrounding management of patients with AAA following a 75-min simulation-based curriculum. [ABSTRACT FROM AUTHOR]

Objectives: Patients with primary muscle tension dysphonia (pMTD) commonly report paralaryngeal pain and discomfort, and extrinsic laryngeal muscle (ELM) tension and hyperfunction are commonly implicated. However, quantitative physiological metrics to study ELM movement patterns for the characterization of pMTD diagnosis and monitoring of treatment progress are lacking. The objectives of this study were to validate motion capture (MoCap) technology to study ELM kinematics, determine whether MoCap could distinguish ELM tension and hyperfunction between individuals with and without pMTD, and investigate relationships between common clinical voice metrics and ELM kinematics. Methods: Thirty subjects (15 with pMTD and 15 controls) were recruited for the study. Sixteen markers were placed on different anatomical landmarks on the chin and anterior neck. Movements across these regions were tracked during four voice and speech tasks using two three‐dimensional cameras. Movement displacement and variability were determined based on 16 key‐points and 53 edges. Results: Intraclass correlation coefficients demonstrated high intra‐ and inter‐rater reliability (p's < 0.001). Other than greater movement displacements around the thyrohyoid space during longer phrasing (reading passage, 30‐s diadochokinetics) and more movement variability in patients with pMTD, kinematic patterns between groups were similar across the 53 edges for the four voice and speech tasks. There were also no significant correlations between ELM kinematics and standard voice metrics. Conclusion: Results demonstrate the feasibility and reliability of MoCap for the study of ELM kinematics. Level of Evidence: 3 Laryngoscope, 133:3472–3481, 2023 [ABSTRACT FROM AUTHOR]

Objectives: It has been assumed that patients with primary muscle tension dysphonia (pMTD) have more extrinsic laryngeal muscle (ELM) tension, but tools to study this phenomenon lack. Shear wave elastography (SWE) is a potential method to address these shortcomings. The objectives of this study were to apply SWE to the ELMs, compare SWE measures to standard clinical metrics, and determine group differences in pMTD and typical voice users before and after vocal load. Methods: SWE measurements of the ELMs from ultrasound examinations of the anterior neck, supraglottic compression severities from laryngoscopic images, cepstral peak prominences (CPP) from voice recordings, and self‐perceptual ratings of vocal effort and discomfort were obtained in voice users with (N = 30) and without (N = 35) pMTD, before and after a vocal load challenge. Results: ELM tension significantly increased from rest‐to‐voiced conditions in both groups. However, the groups were similar in their ELM stiffness levels at SWE at baseline, during vocalization, and post‐vocal load. Levels of vocal effort and discomfort and supraglottic compression were significantly higher and CPP was significantly lower in the pMTD group. Vocal load had a significant effect on vocal effort and discomfort but not on laryngeal or acoustic patterns. Conclusion: SWE can be used to quantify ELM tension with voicing. Although the pMTD group reported significantly higher levels of vocal effort and vocal tract discomfort and, on average, exhibited significantly more severe supraglottic compression and lower CPP values, there were no group differences in levels of ELM tension using SWE. Level of Evidence: 2 Laryngoscope, 133:3482–3491, 2023 [ABSTRACT FROM AUTHOR]

Background/Objectives: False vocal fold (FVF) hyperfunction during phonation is thought to be a diagnostic sign of primary muscle tension dysphonia (pMTD). However, hyperfunctional patterns with phonation are also observed in typical speakers. This study tested the hypothesis that FVF posturing during quiet breathing, as measured by the curvature of FVF, could differentiate patients with pMTD from typical speakers. Methods: Laryngoscopic images were collected prospectively in 30 subjects with pMTD and 33 typical speakers. Images were acquired at the end of expiration and maximal inspiration during quiet breathing, during sustained /i/, and during loud phonation before and after a 30‐min vocal loading task. The FVF curvature (degree of concavity/convexity) was quantified using a novel curvature index (CI, >0 for hyperfunctional/convex, <0 for "relaxed"/concave) and compared between the two groups. Results: At end‐expiration, the pMTD group adopted a convex FVF contour, whereas the control group adopted a concave FVF contour (mean CI 0.123 [SEM 0.046] vs. −0.093 [SEM 0.030], p = 0.0002) before vocal loading. At maximal inspiration, the pMTD group had a neutral/straight FVF contour, whereas the control group had a concave FVF contour (mean CI 0.012 [SEM 0.038] vs. −0.155 [SEM 0.018], p = 0.0002). There were no statistically significant differences in FVF curvature between groups in either the sustained voiced or loud conditions. Vocal loading did not change any of these relationships. Conclusions: A hyperfunctional posture of the FVFs during quiet breathing especially at end‐expiration may be more indicative of a hyperfunctional voice disorder than supraglottic constriction during voicing. Level of Evidence: 3 Laryngoscope, 133:3449–3454, 2023 [ABSTRACT FROM AUTHOR]

Background We evaluated the relationship between response to efflux pump inhibition in fluoroquinolone-resistant Mycobacterium tuberculosis (Mtb) isolates and differences in gene expression and expression quantitative trait loci (eQTL). Methods We determined ofloxacin minimum inhibitory concentration (MIC) for ofloxacin-resistant and -susceptible Mtb isolates without and with the efflux pump inhibitor verapamil. We performed RNA sequencing (RNA-seq), whole genome sequencing (WGS), and eQTL analysis, focusing on efflux pump, transport, and secretion-associated genes. Results Of 42 ofloxacin-resistant Mtb isolates, 27 had adequate WGS coverage and acceptable RNA-seq quality. Of these 27, 7 had >2-fold reduction in ofloxacin MIC with verapamil; 6 had 2-fold reduction, and 14 had <2-fold reduction. Five genes (including Rv0191) had significantly increased expression in the MIC fold change >2 compared to <2 groups. Among regulated genes, 31 eQTLs (without ofloxacin) and 35 eQTLs (with ofloxacin) had significant allele frequency differences between MIC fold change >2 and <2 groups. Of these, Rv1410c , Rv2459 , and Rv3756c (without ofloxacin) and Rv0191 and Rv3756c (with ofloxacin) have previously been associated with antituberculosis drug resistance. Conclusions In this first reported eQTL analysis in Mtb , Rv0191 had increased gene expression and significance in eQTL analysis, making it a candidate for functional evaluation of efflux-mediated fluoroquinolone resistance in Mtb. [ABSTRACT FROM AUTHOR]

The article focuses on Thomas De Quincey's fascination with power and his alignment with it, evident in his writings on opium and other areas. Topics include De Quincey's views on the literature of power, his admiration for Wordsworth as the greatest English poet, and the role of continuousness in producing sustained and elaborate expressions of thought and emotion.

Prior empirical research found that in the United States, rural community banks earn higher profits than their metropolitan counterparts and have lower risk loan portfolios as well. Investigating community bank failures since 2000 we find support for the competition-fragility view that increased competition in banking correlates with an increase in bank failures based on the finding that preponderance of US bank failures are community banks in metropolitan areas where they face direct competition from multiple large banks. This study tests seven hypotheses using a nationwide survey of community bankers. The results indicate metropolitan bankers perceive an intense competitive environment where it is difficult to get their message to potential new clients while also losing their most creditworthy business clients to mega-banks. Bankers across geographic regions suggest that economies of scale in technology and regulatory compliance drive merger and acquisition activity and it will continue despite the shocking reduction of over 70% of banks since deregulation through mergers, acquisitions, and failures. Prior research also suggests that larger banks extend less credit to small businesses. If true, fewer metropolitan community banks will further restrict the bank credit available to new businesses and existing microenterprises, especially in the metropolitan areas where 86% of the US population now live. This study provides additional support for the position that US community banks are not a homogenous group and studies need to consider the geographic scope of operation. Based on these results and the relevant literature, we provide suggestions for community bankers, entrepreneurs, regulators, and future research. [ABSTRACT FROM AUTHOR]

An effective vaccine is needed for the prevention and elimination of malaria. The only immunogens that have been shown to have a protective efficacy of more than 90% against human malaria are Plasmodium falciparum (Pf) sporozoites (PfSPZ) manufactured in mosquitoes (mPfSPZ)1–7. The ability to produce PfSPZ in vitro (iPfSPZ) without mosquitoes would substantially enhance the production of PfSPZ vaccines and mosquito-stage malaria research, but this ability is lacking. Here we report the production of hundreds of millions of iPfSPZ. iPfSPZ invaded human hepatocytes in culture and developed to mature liver-stage schizonts expressing P. falciparum merozoite surface protein 1 (PfMSP1) in numbers comparable to mPfSPZ. When injected into FRGhuHep mice containing humanized livers, iPfSPZ invaded the human hepatocytes and developed to PfMSP1-expressing late liver stage parasites at 45% the quantity of cryopreserved mPfSPZ. Human blood from FRGhuHep mice infected with iPfSPZ produced asexual and sexual erythrocytic-stage parasites in culture, and gametocytes developed to PfSPZ when fed to mosquitoes, completing the P. falciparum life cycle from infectious gametocyte to infectious gametocyte without mosquitoes or primates.Plasmodium falciparum sporozoites produced in vitro recapitulate the P. falciparum life cycle from gametocyte to gametocyte without mosquitoes or primates. [ABSTRACT FROM AUTHOR]

Objective: Surgical procedures that render patients acutely aphonic can cause them to experience significant anxiety and distress. We queried patient perceptions after tracheostomy or laryngectomy and investigated whether introducing augmentative technology was associated with improvement in patient-reported outcomes. Methods: Participants included hospitalized patients who acutely lost the ability to speak due to tracheostomy or total laryngectomy from April 2018 to December 2019. We distributed questions regarding the patient communication experience and relevant questions from the validated V-RQOL questionnaire (Voice-Related Quality of Life). Patients were offered a tablet with the electronic communication application Verbally. Pre- and postintervention groups were compared with chi-square analyses. Results: Surveys were completed by 35 patients (n = 18, preintervention; n = 17, postintervention). Prior to using augmentative technology, 89% of patients who were aphonic reported difficulty communicating, specifically noting breathing or suctioning (56%), treatment and discharge plans (78%), or immediate needs, such as pain and using the bathroom (39%). Communication difficulties caused anxiety (55%), depression (44%), or frustration (62%), and 92% of patients were interested in using an electronic communication device. Patients reported less trouble communicating after the intervention versus before (53% vs 89%, P =.03), including less difficulty communicating about treatment or discharge plans (35% vs 78%, P <.01). V-RQOL scores were unchanged. Discussion: Acute loss of phonation arising from surgery can be highly distressing for patients, and use of augmentative technology may alleviate some of these challenges by improving communication. Further studies are needed to identify what additional strategies may improve overall well-being. Implications for Practice: Electronic communication devices may benefit patients with acute aphonia. [ABSTRACT FROM AUTHOR]

Prior studies of A:B::C:D verbal analogies have identified several factors that affect performance, including the semantic similarity between source and target domains (semantic distance), the semantic association between the C-term and incorrect answers (distracter salience), and the type of relations between word pairs. However, it is unclear how these stimulus properties affect performance when utilized together. To test their interactive effects, we created a verbal analogy stimulus set that factorially crossed these factors and presented participants with an analogical stem (A:B::C:?) with two response choices: an analogically correct (D) and incorrect distracter (D′) term. The semantic distance between source and target word pairs was manipulated creating near (bowl:dish::spoon:silverware) and far (wrench:tool::sad:mood) analogies. The salience of an incorrect distracter (D′) was manipulated using the sematic distance with the C-term creating low (drawer) and high (fork) salience distracters. Causal, compositional, and categorical relations were presented across these conditions. Accuracies were higher for semantically near than far analogies and when distracter salience was low than high. Categorical relations yielded better performance than the causal and compositional relations. Moreover, a three-way interaction demonstrated that the effects of semantic distance and distracter salience had a greater impact on performance for compositional and causal relations than for the categorical ones. We theorize that causal and compositional analogies, given their less semantically constrained responses, require more inhibitory control than more constraining relations (e.g., categorical). [ABSTRACT FROM AUTHOR]

In this concluding article for the special issue on COVID-19 and K-12 arts education, the authors look forward to some positive possible changes for the delivery of arts education as students return to school past COVID-19 and will address some of the barriers to these positive changes, including policy opportunities and implications. The barriers discussed are not new to arts education – resource and funding challenges, a focus on remediation pulling students from arts classes, and a continued inequitable access to arts education for students in poverty and students of color. The article will discuss how the pandemic has exacerbated some of these long-standing challenges, as well as ways to address those challenges from a policy perspective as well as through advocacy work at the federal, state, and local levels. The article suggests ways to rethink how we approach areas of educational policy, particularly the accountability structures of public education, in order to address inequitable access now and in the long term. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the pattern of presentation and management of laryngotracheobronchial amyloidosis at a tertiary care academic center over a 27 year period. Methods: In a retrospective review, the electronic medical record at a tertiary care academic center was queried for encounters with 3 laryngologists between 1996 and 2019 which included the ICD-9 or ICD-10 diagnosis of amyloidosis. Demographics, clinical presentation, referral diagnoses, medical history, family history, laboratory values, radiology studies, and treatment modalities of subjects were collated. Results were analyzed using standard univariate descriptive statistics. Results: Seventeen subjects were identified with an average age at diagnosis of 58 years (range 26-76 years). The most common amyloid type on biopsy was immunoglobulin light chain (AL) subtype. The most common location of laryngeal amyloid at diagnosis was the glottis and disease was more likely to be bilateral at the time of diagnosis in this location. Supraglottic disease more often had a unilateral presentation and had a tendency to spread to additional laryngeal subsites. Nearly 25% of subjects had associated systemic disease, including multiple myeloma, auto-immune disease, and familial ATTR mutation. Conclusions: The overall rate of associated systemic disease was low in our study cohort; however, it is higher than typically referenced in extant literature. Our cohort demonstrates that while laryngeal amyloidosis is a chronic condition, the behavior is generally indolent with a low treatment burden. [ABSTRACT FROM AUTHOR]

Nerve injury affecting the upper limb is a leading cause of lifelong disability. Damage to the nerves in the arm often causes weakness and somatosensory dysfunction ranging from numbness to pain. Previous studies show that combining brief bursts of electrical vagus nerve stimulation (VNS) with motor or tactile rehabilitation can restore forelimb function after median and ulnar nerve injury, which causes hyposensitivity of the ventral forelimb. Here, we sought to determine whether this approach would be similarly effective in a model of radial nerve injury that produces allodynia in the ventral forelimb. To test this, rats underwent complete transection of the radial nerve proximal to the elbow followed by tubular repair. In the first experiment, beginning ten weeks after injury, rats received six weeks of tactile rehabilitation, consisting of mechanical stimulation of either the dorsal or ventral region of the forepaw in the injured limb, with or without concurrent VNS. In a second experiment, a separate cohort of rats underwent six weeks of forelimb motor rehabilitative training with or without paired VNS. Contrary to findings in previous models of hyposensitivity, VNS therapy fails to improve recovery of either somatosensory or motor function in the forelimb after radial nerve injury. These findings describe initial evidence that pain may limit the efficacy of VNS therapy and thus highlight a characteristic that should be considered in future studies that seek to develop this intervention. [ABSTRACT FROM AUTHOR]

Background: Plasmodium falciparum-infected red blood cells (iRBCs) bind and sequester in deep vascular beds, causing malaria-related disease and death. In pregnant women, VAR2CSA binds to chondroitin sulfate A (CSA) and mediates placental sequestration, making it the major placental malaria (PM) vaccine target.Methods: In this study, we characterize an invariant protein associated with PM called P falciparum chondroitin sulfate A ligand (PfCSA-L).Results: Recombinant PfCSA-L binds both placental CSA and VAR2CSA with nanomolar affinity, and it is coexpressed on the iRBC surface with VAR2CSA. Unlike VAR2CSA, which is anchored by a transmembrane domain, PfCSA-L is peripherally associated with the outer surface of knobs through high-affinity protein-protein interactions with VAR2CSA. This suggests that iRBC sequestration involves complexes of invariant and variant surface proteins, allowing parasites to maintain both diversity and function at the iRBC surface.Conclusions: The PfCSA-L is a promising target for intervention because it is well conserved, exposed on infected cells, and expressed and localized with VAR2CSA. [ABSTRACT FROM AUTHOR]

Copyright of Canadian Veterinary Journal / Revue Vétérinaire Canadienne is the property of Canadian Veterinary Medical Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Rats produce ultrasonic vocalizations (USVs) for conspecific communication. These USVs are valuable biomarkers for studying behavioral and mechanistic changes in a variety of diseases and disorders. Previous work has demonstrated operant conditioning can progressively increase the number of USVs produced by rats over multiple weeks. This operant conditioning paradigm is a useful model for investigating the effects of increased laryngeal muscle use on USV acoustic characteristics and underlying central and peripheral laryngeal sensorimotor mechanisms. Previous USV operant conditioning studies relied on manual training to elicit USV productions, which is both time and labor intensive and can introduce human variability. This manuscript introduces a semi-automated method for training rats to increase their rate of USV production by pairing commercially available operant conditioning equipment with an ultrasonic detection system. USV training requires three basic components: elicitation cue, detection of the behavior, and a reward to reinforce the desired behavior. With the semi-automated training paradigm, indirect exposure to the opposite sex or an olfactory cue can be used to elicit USV production. The elicited USV is then automatically detected by the ultrasonic acoustic system, which consequently triggers the release of a sucrose pellet reward. Our results demonstrate this semi-automated procedure produces a similar increase in USV production as the manual training method. Through automation of USV detection and reward administration, staffing requirements, human error, and subject behavioral variability may be minimized while scalability and reproducibility are increased. This automation may also result in greater experimental flexibility, allowing USV training paradigms to become more customizable for a wider array of applications. This semi-automated USV behavioral training paradigm improves upon manual training techniques by increasing the ease, speed, and quality of data collection. [ABSTRACT FROM AUTHOR]

Vagus nerve stimulation (VNS) delivered during motor rehabilitation enhances recovery from a wide array of neurological injuries and was recently approved by the U.S. FDA for chronic stroke. The benefits of VNS result from precisely timed engagement of neuromodulatory networks during rehabilitative training, which promotes synaptic plasticity in networks activated by rehabilitation. Previous studies demonstrate that lesions that deplete these neuromodulatory networks block VNS-mediated plasticity and accompanying enhancement of recovery. There is a great deal of interest in determining whether commonly prescribed pharmacological interventions that influence these neuromodulatory networks would similarly impair VNS effects. Here, we sought to directly test the effects of three common pharmaceuticals at clinically relevant doses that target neuromodulatory pathways on VNS-mediated plasticity in rats. To do so, rats were trained on a behavioral task in which jaw movement during chewing was paired with VNS and received daily injections of either oxybutynin, a cholinergic antagonist, prazosin, an adrenergic antagonist, duloxetine, a serotonin-norepinephrine reuptake inhibitor, or saline. After the final behavioral session, intracortical microstimulation (ICMS) was used to evaluate reorganization of motor cortex representations, with area of cortex eliciting jaw movement as the primary outcome. In animals that received control saline injections, VNS paired with training significantly increased the movement representation of the jaw compared to naïve animals, consistent with previous studies. Similarly, none of the drugs tested blocked this VNS-dependent reorganization of motor cortex. The present results provide direct evidence that these common pharmaceuticals, when used at clinically relevant doses, are unlikely to adversely impact the efficacy of VNS therapy. [ABSTRACT FROM AUTHOR]

Mechanisms underlying variability in transmission of Mycobacterium tuberculosis strains remain undefined. By characterizing high and low transmission strains of M.tuberculosis in mice, we show here that high transmission M.tuberculosis strain induce rapid IL-1R-dependent alveolar macrophage migration from the alveolar space into the interstitium and that this action is key to subsequent temporal events of early dissemination of bacteria to the lymph nodes, Th1 priming, granulomatous response and bacterial control. In contrast, IL-1R-dependent alveolar macrophage migration and early dissemination of bacteria to lymph nodes is significantly impeded in infection with low transmission M.tuberculosis strain; these events promote the development of Th17 immunity, fostering neutrophilic inflammation and increased bacterial replication. Our results suggest that by inducing granulomas with the potential to develop into cavitary lesions that aids bacterial escape into the airways, high transmission M.tuberculosis strain is poised for greater transmissibility. These findings implicate bacterial heterogeneity as an important modifier of TB disease manifestations and transmission. Halting tuberculosis transmission is crucial to TB elimination. Here the authors implicate IL-1R dependent T cell priming as the underlying mechanism determining variability in transmission of Mycobacterium tuberculosis strains. [ABSTRACT FROM AUTHOR]

This article is the first to focus on statements about ethical guidance in post-classical astronomy texts. A number of astronomers in post-classical Islamic societies remarked that the study of astronomy, specifically the mathematical analysis of the uniform motions of the celestial orbs, had ethical benefits. These astronomers' statements are significant because, through them, scholars can learn more about the role of reason in Islamic thought and about sources of ethical guidance other than Sharīʿa and philosophical ethics. The details of the ethical guidance imparted by the study of astronomy tell us more about the relationship between astronomy and the disciplines of fiqh and kalām , respectively. The existence of ethical guidance in astronomy texts is additional evidence that post-classical astronomy texts were part of an Islamic intellectual tradition. [ABSTRACT FROM AUTHOR]

Background Alternative polyadenylation (APA) causes shortening or lengthening of the 3ʹ-untranslated region (3ʹ-UTR) of genes (APA genes) in diverse cellular processes such as cell proliferation and differentiation. To identify cell-type–specific APA genes in scRNA-Seq data, current bioinformatic methods have several limitations. First, they assume certain read coverage shapes in the scRNA-Seq data, which can be violated in multiple APA genes. Second, their identification is limited between 2 cell types and not directly applicable to the data of multiple cell types. Third, they do not control undesired source of variance, which potentially introduces noise to the cell-type–specific identification of APA genes. Findings We developed a combination of a computational change-point algorithm and a statistical model, single-cell Multi-group identification of APA (scMAPA). To avoid the assumptions on the read coverage shape, scMAPA formulates a change-point problem after transforming the 3ʹ biased scRNA-Seq data to represent the full-length 3ʹ-UTR signal. To identify cell-type–specific APA genes while adjusting for undesired source of variation, scMAPA models APA isoforms in consideration of the cell types and the undesired source. In our novel simulation data and data from human peripheral blood mononuclear cells, scMAPA outperforms existing methods in sensitivity, robustness, and stability. In mouse brain data consisting of multiple cell types sampled from multiple regions, scMAPA identifies cell-type–specific APA genes, elucidating novel roles of APA for dividing immune cells and differentiated neuron cells and in multiple brain disorders. Conclusions scMAPA elucidates the cell-type–specific function of APA events and sheds novel insights into the functional roles of APA events in complex tissues. [ABSTRACT FROM AUTHOR]

Plasmodium falciparum-infected erythrocytes (IE) sequester in the placenta via surface protein VAR2CSA, which binds chondroitin sulfate A (CSA) expressed on the syncytiotrophoblast surface, causing placental malaria (PM) and severe adverse outcomes in mothers and their offspring. VAR2CSA belongs to the PfEMP1 variant surface antigen family; PfEMP1 proteins mediate IE adhesion and facilitate parasite immunoevasion through antigenic variation. Here we produced deglycosylated (native-like) and glycosylated versions of seven recombinant full-length VAR2CSA ectodomains and compared them for antigenicity and adhesiveness. All VAR2CSA recombinants bound CSA with nanomolar affinity, and plasma from Malian pregnant women demonstrated antigen-specific reactivity that increased with gravidity and trimester. However, allelic and glycosylation variants differed in their affinity to CSA and their serum reactivities. Deglycosylated proteins (native-like) showed higher CSA affinity than glycosylated proteins for all variants except NF54. Further, the gravidity-related increase in serum VAR2CSA reactivity (correlates with acquisition of protective immunity) was absent with the deglycosylated form of atypical M200101 VAR2CSA with an extended C-terminal region. Our findings indicate significant inter-allelic differences in adhesion and seroreactivity that may contribute to the heterogeneity of clinical presentations, which could have implications for vaccine design. Full-length VAR2CSA is a potential placental malaria vaccine candidate and in this study, Renn et al. compare antigenicity and receptor binding affinity of different allelic variants in blood samples from pregnant women. Their data show that inter-allelic differences may contribute to the heterogeneity of clinical presentations, which could have implications for vaccine design. [ABSTRACT FROM AUTHOR]

Thomas De Quincey exploits his rivalry with Samuel Taylor Coleridge to structure many of the key features of his most famous work, 'Confessions of an English Opium-Eater' (1821). De Quincey's idolization of Coleridge began early and survived the anger and disappointment he felt after the collapse of their friendship and his discovery of Coleridge's intellectual duplicity. In 'Confessions', De Quincey's accounts of himself as a scholar of Greek literature, Ricardian economics, and Kantean philosophy are all galvanized by his knowledge that Coleridge too has worked in these areas. As opium addicts, De Quincey's experience of the drug overlaps with Coleridge's in a number of ways, while De Quincey differs from Coleridge – at least on the surface – in his claims about both the moral implications of drugged euphoria and the resolve needed to defeat addiction. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: Patients with tracheostomies have an anatomically altered connection between their upper and lower airways that could impact SARS-CoV-2 testing. Our goal was to evaluate for discordance in SARS-CoV-2 detection in hospitalized patients with COVID-19 and tracheostomies based on the site analyzed.Study Design: Retrospective chart review METHODS: This single-institution study evaluated hospitalized patients with COVID-19 who had tracheostomies placed during their treatment. We analyzed SARS-CoV-2 RNA nucleic acid amplification test (NAAT) results after tracheostomy. All included patients had nasopharyngeal (NP) and tracheal (TR) samples taken within a 48-hour period, allowing us to characterize rate of test concordance.Results: Forty-five patients met our inclusion criteria. Thirty-two (71.1%) patients had entirely concordant results after tracheostomy. However, 13 (28.9%) patients had at least one set of discordant results, the majority of which were NP negative and TR positive. There were no statistically significant differences in demographic or clinical variables, including time to tracheostomy and time to testing, among patients with concordant versus discordant SARS-CoV-2 results.Conclusion: This represents the first study to examine SARS-CoV-2 RNA NAAT concordance between NP and TR sites in hospitalized patients with COVID-19 and tracheostomies. One-third of patients demonstrated discordant testing when NP and TR specimens were collected within a 48-hour time period. Thus, patients with tracheostomies may have a higher false-negative rate if only one site is assessed for SARS-CoV-2. We recommend analyzing samples from both the nasopharynx and trachea for these patients until more prospective data exist.Level Of Evidence: IV Laryngoscope, 2021. [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis: To evaluate the safety and complications of endoscopic airway surgery using supraglottic jet ventilation with a team‐based approach. Study Design: Retrospective cohort study. Methods: Subjects at two academic institutions diagnosed with laryngotracheal stenosis who underwent endoscopic airway surgery with jet ventilation between January 2008 and December 2018 were identified. Patient characteristics (age, gender, race, follow‐up duration) and comorbidities were extracted from the electronic health record. Records were reviewed for treatment approach, intraoperative data, and complications (intraoperative, acute postoperative, and delayed postoperative). Results: Eight hundred and ninety‐four patient encounters from 371 patients were identified. Intraoperative complications (unplanned tracheotomy, profound or severe hypoxic events, barotrauma, laryngospasm) occurred in fewer than 1% of patient encounters. Acute postoperative complications (postoperative recovery unit [PACU] rapid response, PACU intubation, return to the emergency department [ED] within 24 hours of surgery) were rare, occurring in fewer than 3% of patient encounters. Delayed postoperative complications (return to the ED or admission for respiratory complaints within 30 days of surgery) occurred in fewer than 1% of patient encounters. Diabetes mellitus, active smoking, and history of previous tracheotomy were independently associated with intraoperative, acute, and delayed complications. Conclusions: Employing a team‐based approach, jet ventilation during endoscopic airway surgery demonstrates a low rate of complications and provides for safe and successful surgery. Level of Evidence: 4 Laryngoscope, 131:2292–2297, 2021 [ABSTRACT FROM AUTHOR]

Accurate densities were determined from configuration interaction wave functions for atoms and ions of Li, Be, and B with up to four electrons. Exchange-correlation potentials, Vxc(r), and functional derivatives of the noninteracting kinetic energy, δK[p]/δp(r), obtained from these densities were used to examine their discontinuities as the number of electrons N increases across integer boundaries for N = 1, N = 2, and N = 3. These numerical results are consistent with conclusions that the discontinuities are characterized by a jump in the chemical potential while the shape of Vxc(r) varies continuously as an integer boundary is crossed. The discontinuity of the Vxc(r) is positive, depends on the ionization potential, electron affinity, and orbital energy differences, and the discontinuity in δK[p]/δp(r) depends on the difference between the energies of the highest occupied and lowest unoccupied orbitals. The noninteracting kinetic energy and the exchange correlation energy have been computed for integer and noninteger values of N between 1 and 4. [ABSTRACT FROM AUTHOR]

This article argues that astronomers' discourses about cosmology, specifically their arguments for an ordered cosmos comprised of uniformly revolving orbs, were in a conversation with ʿilm al-kalām during the period under discussion, which is from the end of the fourteenth century through the mid-sixteenth century. In kalām , Taftāzānī's Sharḥ al-Maqāṣid contended that the astronomers' views of cosmic order were but a conviction (iʿtiqād) for which there was no demonstration. Mīrim Çelebī's commentary on the popular astronomy text al-Risāla al-Fatḥiyya noted, however, the theological value of the astronomers' ordered cosmos. Another astronomer contemporary with Mīrim Çelebī, Bīrjandī, was well-versed in kalām texts and certainly agreed with other astronomers about how the cosmos was ordered. Yet Bīrjandī did not explore the theological ramifications of an ordered cosmos. [ABSTRACT FROM AUTHOR]

Stroke often leaves lasting impairments affecting orofacial function. While speech therapy is able to enhance function after stroke, many patients see only modest improvements after treatment. This partial restoration of function after rehabilitation suggests that there is a need for further intervention. Rehabilitative strategies that augment the effects of traditional speech therapy hold promise to yield greater efficacy and reduce disability associated with motor speech disorders. Recent studies demonstrate that brief bursts of vagus nerve stimulation (VNS) can facilitate the benefits of rehabilitative interventions. VNS paired with upper limb rehabilitation enhances recovery of upper limb function in patients with chronic stroke. Animal studies reveal that these improvements are driven by VNS-dependent synaptic plasticity in motor networks. Moreover, preclinical evidence demonstrates that a similar strategy of pairing VNS can promote synaptic reorganization in orofacial networks. Building on these findings, we postulate that VNS-directed orofacial plasticity could target post-stroke motor speech disorders. Here, we outline the rationale for pairing VNS with traditional speech therapy to enhance recovery in the context of stroke of speech motor function. We also explore similar treatments that aim to enhance synaptic plasticity during speech therapy, and how VNS differs from these existing therapeutic strategies. Based on this evidence, we posit that VNS-paired speech therapy shows promise as a means of enhancing recovery after post-stroke motor speech disorders. Continued development is necessary to comprehensively establish and optimize this approach, which has the potential to increase quality of life for the many individuals suffering with these common impairments. [ABSTRACT FROM AUTHOR]

Objectives: To report preliminary outcomes of a case series of in-office intralesional steroid injections for treatment of laryngeal sarcoidosis. Methods: After diagnosis of laryngeal sarcoidosis, 3 patients were offered in-office steroid injections for primary or adjunctive treatment. Triamcinolone 40 was injected into supraglottic sarcoidosis lesions in the office using a channel laryngoscope. Response to treatment and need for further injections was determined based on patient symptoms and repeat flexible laryngoscopy. Results: In-office intralesional steroid injections provided rapid symptom relief within days that lasted for months, thus decreasing the frequency of operative interventions. For one of the patients in this series, these injections even eliminated the need for tracheostomy. No complications were observed. Conclusions: In-office intralesional steroid injection is an emerging adjunctive treatment for laryngeal sarcoidosis. Prospective studies are required to determine efficacy and long-term risk profiles in relation to the current standard of operative management and systemic treatments. [ABSTRACT FROM AUTHOR]

This study explored differences in sustained top‐down attentional control (i.e., proactive control) and spontaneous types of control (i.e., reactive control) in bilingual and monolingual speakers. We modified a Color‐Word Stroop task to varying levels of conflict and included switching trials in addition to more "traditional" inhibition Stroop conditions. The task was administered during scalp electroencephalography (EEG) to evaluate the temporal course of cognitive control during trials. The behavioral Stroop effect was observed across the whole sample; however, there were no differences in accuracy or response time between the bilingual and monolingual groups. Event‐related potentials (ERPs) were calculated for the N200, N450, and conflict Sustained Potential (SP). On the pure‐blocked incongruent trials, the bilingual group displayed reduced signal during interference suppression (N450) and increased later signal, as indexed by the conflict SP. On the mixed‐block incongruent trials, both the bilinguals and monolinguals displayed increased later signal at the conflict SP. This suggests that proactive control may be a default mode for bilinguals on tasks requiring inhibition. In the switching trials, that place high demands on the executive control component of shifting, the language groups did not differ. Overall, these results suggest processing differences between bilinguals and monolinguals extend beyond early response inhibition processes. Greater integration of proactive and reactive control may be needed to sort conflicting language environments for bilinguals, which may be transferring to domain‐general mechanisms. This ERP study advances the literature on bilingual and monolingual processing of conflicting stimuli by demonstrating that language group differences extend beyond initial response inhibition processes. Bilinguals defaulted to greater proactive control activity on the inhibition trials of a Stroop task, which facilitated reductions in interference suppression. A greater integration of proactive and reactive control may be needed to sort conflicting language environments for bilinguals, which may be transferring to domain‐general mechanisms. [ABSTRACT FROM AUTHOR]

Objectives: To characterize the impact of subglottic stenosis (SGS) on voice‐related quality of life (V‐RQOL) and quantify the effect of treatment on voice outcomes. Study Design: Case series. Methods: Retrospective review of SGS patients treated from 1996 to 2018 at a single institution to assess for 1) V‐RQOL association with individual patient cumulative treatment number and 2) V‐RQOL correlation with treatment type, time between treatments, and degree of stenosis. Analysis included both parametric and nonparametric statistical comparison across treatment types and multivariable and univariate linear regression. Results: Sixty‐one patients, predominantly white (93%) and female (93%), were included. Etiology of SGS included idiopathic (61%), iatrogenic (16%), granulomatosis with polyangiitis (16%), and other (7%). The plurality of patients had four or more treatments (44%), with the remainder having one (28%), two (13%), or three treatments (15%). Analysis of change between pre‐ and postoperative V‐RQOL scores was completed for 130 treatments. These included dilation with laser incision (52%), in‐office injection (34%), dilation without division (8%), cricotracheal resection (1%), and all other treatment (8%). For every 10% improvement in airway caliber postoperatively, there was a 1.3‐point improvement in calculated V‐RQOL (r = 0.27, P =.02). After adjustment for treatment type, age, sex, and SGS etiology, this association held (beta = 1.5, P =.02). Change in V‐RQOL was not associated with treatment type, treatment number, or time between treatments. Conclusion: Patients with subglottic stenosis who have greater degree of change in airway caliber experience greater improvement in V‐RQOL scores following treatment. V‐RQOL scores are not associated with treatment type or time between individual treatments. Level of Evidence: 4 Laryngoscope, 131:360–365, 2021 [ABSTRACT FROM AUTHOR]

Copyright of Journal of the Royal Asiatic Society Hong Kong is the property of Royal Asiatic Society Hong Kong and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Although vaccination is the main measure to control influenza A virus (IAV) in swine, there is limited information on the efficacy of sow vaccination on reducing IAV infections in pigs at weaning. We assessed the effect of sow vaccination on IAV infection in pigs at weaning in a cohort of 52 breeding herds studied prospectively. Herds were voluntarily enrolled according to their IAV history, sow vaccination protocol and monitored during six months (prospective longitudinal study). On each herd, nasal swabs were collected monthly from 30 pigs at weaning and tested for IAV by RT‐PCR. IAV was detected in 25% (75/305) of sampling events. Of 9,150 nasal swab pools (3 individual nasal swabs/pool), 15% (458/3050) of pools tested IAV positive. IAV infections in pigs at weaning were lower in vaccinated herds compared to non‐vaccinated ones. Moreover, no significant differences were seen between prefarrow and whole herd protocols, or the use of commercial versus autogenous IAV vaccines. Prefarrow and whole herd vaccination protocols reduced the odds of groups testing IAV positive at weaning in comparison with no vaccination. Our results are relevant when considering implementation of sow vaccination to control influenza infections in pigs at weaning and, hence, minimize transmission to growing pigs and other farms. [ABSTRACT FROM AUTHOR]

University of Michigan Multidisciplinary Head and Neck Oncology Tumor Board Multidisciplinary head and neck TB conferences occur weekly at our institution in a virtual format led by a head and neck surgeon and last approximately 2 hours. Multidisciplinary tumor boards (TBs) have increasingly become the standard of care for developing optimal treatment plans for complex cancer patients.[1] [3] Head and neck cancer treatment frequently involves multidisciplinary care, highlighting the importance of a comprehensive TB. Here, we present a simplified, expert-driven TB documentation workflow that automates oncologic data capture and reporting. [Extracted from the article]

Expert-driven, electronic tumor board documentation automates oncologic data capture and reporting. [ABSTRACT FROM AUTHOR]

Expert-driven, electronic tumor board documentation automates oncologic data capture and reporting. [ABSTRACT FROM AUTHOR]

This study summarizes piecework incentive systems and examines two apparel manufacturing factories that used daily incentive calculations at one time and weekly incentive calculations at another. In addition, one factory implemented a multiple base-rate incentive system, often called jump-base. The data shows that, when not controlled, daily incentive can facilitate operators engaging in fraudulent activity such as ticket-holding. With fraud controlled, daily incentive calculation makes little difference in overall pay; therefore, it may have individual level motivational effects by nullifying the effect of averaging one-bad-day into the week. While jumpbase may enhance productivity in lower performing operators or modules, one must take great care when designing such systems. [ABSTRACT FROM AUTHOR]