bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptomic and epigenomic dynamics associated with development of human iPSC-derived GABAergic interneurons
Authors: Inglis George Andrew S , Zhou Ying , Patterson Dillon G , Scharer Christopher D , Han Yanfei , Boss Jeremy M , Wen Zhexing , Escayg Andrew
Published: July 2020

GABAergic interneurons (GINs) are a heterogeneous population of inhibitory neurons that collectively contribute to the maintenance of normal neuronal excitability and network activity. Identification of the genetic regulatory elements and transcription factors that contribute toward GIN function may provide new insight into the pathways underlying proper GIN activity while also indicating potential therapeutic targets for GIN-associated disorders, such as schizophrenia and epilepsy. In this study, we examined the temporal changes in gene expression and chromatin accessibility during GIN development by performing transcriptomic and epigenomic analyses on human induced pluripotent stem cell-derived neurons at 22, 50 and 78 days (D) post-differentiation. We observed 13 221 differentially accessible regions (DARs) of chromatin that associate with temporal changes in gene expression at D78 and D50, relative to D22. We also classified families of transcription factors that are increasingly enriched at DARs during differentiation, indicating regulatory networks that likely drive GIN development. Collectively, these data provide a resource for examining the molecular networks regulating GIN functionality.
Global Seasonality of Human Seasonal Coronaviruses: A Clue for Postpandemic Circulating Season of Severe Acute Respiratory Syndrome Coronavirus 2?
Authors: Li You , Wang Xin , Nair Harish
Published: July 2020

Background

The ongoing pandemic of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could recur as seasonal outbreaks, a circulating pattern observed among other preexisting human seasonal coronaviruses (sCoVs). However, little is known about seasonality of sCoVs on a global scale.

Methods

We conducted a systematic review of data on seasonality of sCoVs. We compared seasonality of sCoVs with influenza virus and respiratory syncytial virus. We modeled monthly activity of sCoVs using site-specific weather data.

Results

We included sCoV seasonality data in 40 sites from 21 countries. sCoVs were prevalent in winter months in most temperate sites except for China, whereas sCoVs tended to be less seasonal in China and in tropical sites. In temperate sites excluding China, 53.1% of annual sCoV cases (interquartile range [IQR], 34.6%–61.9%) occurred during influenza season and 49.6% (IQR, 30.2%–60.2%) of sCoV cases occurred during respiratory syncytial virus season. Low temperature combined with high relative humidity was associated with higher sCoV activity.

Conclusions

This is the first study that provides an overview of the global seasonality of sCoVs. Our findings offer clues to the possible postpandemic circulating season of SARS-CoV-2 and add to the knowledge pool necessary for postpandemic preparedness for SARS-CoV-2.
Efficacy of Antigonococcal CMP-Nonulosonate Therapeutics Require Cathelicidins
Authors: Gulati Sunita , Schoenhofen Ian C , Lindhout-Djukic Theresa , Lewis Lisa A , Moustafa Iesha Y , Saha Sudeshna , Zheng Bo , Nowak Nancy , Rice Peter A , Varki Ajit , Ram Sanjay
Published: July 2020

Novel therapies to counteract multidrug-resistant gonorrhea are urgently needed. A unique gonococcal immune evasion strategy involves capping of lipooligosaccharide (LOS) with sialic acid by gonococcal sialyltransferase (Lst), utilizing host-derived CMP-sialic acid (CMP-Neu5Ac in humans). LOS sialylation renders gonococci resistant to complement and cationic peptides, and down-regulates the inflammatory response by engaging siglecs. CMP-sialic acid analogs (CMP-nonulosonates [CMP-NulOs]) such as CMP-Leg5,7Ac2 and CMP-Kdn are also utilized by Lst. Incorporation of these NulO analogs into LOS maintains gonococci susceptible to complement. Intravaginal administration of CMP-Kdn or CMP-Leg5,7Ac2 attenuates gonococcal colonization of mouse vaginas. Here, we identify a key mechanism of action for the efficacy of CMP-NulOs. Surprisingly, CMP-NulOs remained effective in complement C1q-/- and C3-/- mice. LOS Neu5Ac, but not Leg5,7Ac2 or Kdn, conferred resistance to the cathelicidins LL-37 (human) and mouse cathelicidin-related antimicrobial peptide in vitro. CMP-NulOs were ineffective in Camp-/- mice, revealing that cathelicidins largely mediate the efficacy of therapeutic CMP-NulOs.
Development and evaluation of a quality improvement framework for healthcare
Authors: Hamilton Samantha , Jennings Alison , Forster Alan J
Published: July 2020

Objective

Develop and evaluate a framework for quality improvement which will provide a common approach, terminology and greater likelihood of success in achieving demonstrable and sustained improvement.

Design

Descriptive with mixed methods evaluation.

Setting

Tertiary care academic hospital in Ottawa, Canada.

Participants

Students enrolled in the Quality and Patient Safety Leadership Executive Program at the local university.

Methods

The quality improvement (QI) framework was developed though comparison and coding of key strengths across four commonly applied quality improvement frameworks. Effectiveness of the framework was evaluated through a satisfaction survey of students who were taught the framework, and independent assessment of student improvement initiatives that followed the QI Framework versus initiatives from a prior year who did not.

Main Outcome Measures

Acceptability and effectiveness of the QI Framework.

Results

All participants found the QI Framework to be useful and easy to follow. Independent evaluation of improvement initiatives following the QI Framework, as compared to those that did not, scored higher (95% CI: 3.0 ± 0.49) than the projects completed without the QI Framework (95% CI: 2.2 ± 0.30), P value < 0.01. Scores were higher for cohort 2017/18 in all criteria except scaling and spreading, in which there was no change (2015/16 95% CI: 1.2 ± 0.24, 2017/18 95% CI: 1.2 ± 0.38).

Conclusions

The method we have developed is acceptable and helpful to users, and overall application resulted in higher quality initiatives. We believe this method, which we have branded as The Ottawa Hospital Innovation Framework, can be beneficial in healthcare settings for a variety of change initiatives.
Generating contextual embeddings for emergency department chief complaints
Authors: Chang David , Hong Woo Suk , Taylor Richard Andrew
Published: July 2020

Objective

We learn contextual embeddings for emergency department (ED) chief complaints using Bidirectional Encoder Representations from Transformers (BERT), a state-of-the-art language model, to derive a compact and computationally useful representation for free-text chief complaints.

Materials and methods

Retrospective data on 2.1 million adult and pediatric ED visits was obtained from a large healthcare system covering the period of March 2013 to July 2019. A total of 355 497 (16.4%) visits from 65 737 (8.9%) patients were removed for absence of either a structured or unstructured chief complaint. To ensure adequate training set size, chief complaint labels that comprised less than 0.01%, or 1 in 10 000, of all visits were excluded. The cutoff threshold was incremented on a log scale to create seven datasets of decreasing sparsity. The classification task was to predict the provider-assigned label from the free-text chief complaint using BERT, with Long Short-Term Memory (LSTM) and Embeddings from Language Models (ELMo) as baselines. Performance was measured as the Top-k accuracy from k = 1:5 on a hold-out test set comprising 5% of the samples. The embedding for each free-text chief complaint was extracted as the final 768-dimensional layer of the BERT model and visualized using t-distributed stochastic neighbor embedding (t-SNE).

Results

The models achieved increasing performance with datasets of decreasing sparsity, with BERT outperforming both LSTM and ELMo. The BERT model yielded Top-1 accuracies of 0.65 and 0.69, Top-3 accuracies of 0.87 and 0.90, and Top-5 accuracies of 0.92 and 0.94 on datasets comprised of 434 and 188 labels, respectively. Visualization using t-SNE mapped the learned embeddings in a clinically meaningful way, with related concepts embedded close to each other and broader types of chief complaints clustered together.

Discussion

Despite the inherent noise in the chief complaint label space, the model was able to learn a rich representation of chief complaints and generate reasonable predictions of their labels. The learned embeddings accurately predict provider-assigned chief complaint labels and map semantically similar chief complaints to nearby points in vector space.

Conclusion

Such a model may be used to automatically map free-text chief complaints to structured fields and to assist the development of a standardized, data-driven ontology of chief complaints for healthcare institutions.
Evaluation of the GENE-UP® Listeria monocytogenes Method for the Detection of Listeria monocytogenes in a Variety of Foods and Select Environmental Surfaces: Collaborative Study, First Action 2019.11
Authors: Johnson Ronald , Mills John , Pittet Jean-Louis , Mathia Olivier , Bird Patrick , Nelson Maria
Published: July 2020

Background

The GENE-UP®  Listeria monocytogenes 2 (LMO 2) assay (Performance Tested MethodSM 121804) uses real-time PCR technology and a proprietary detection platform, the GENE-UP Thermocycler, to detect Listeria monocytogenes in a variety of foods and environmental surfaces.

Objective

The purpose of this validation was to evaluate the method’s interlaboratory performance and submit the result to AOAC INTERNATIONAL for adoption as First Action Official MethodSM for the detection of Listeria monocytogenes in a variety of foods and select environmental surfaces.

Method

The GENE-UP method was evaluated in a multi-laboratory study as part of the AFNOR NF VALIDATION certification process using unpaired test portions for one food matrix, full-cream goat milk cottage cheese (8.4% fat). The candidate method was compared to the ISO 11290-1/Amd.1:2004 reference method. Sixteen participants from 15 laboratories throughout the European Union participated. Three levels of contamination were evaluated: a non-inoculated control level (0 CFU/test portion), a low inoculum level (∼2 CFU/test portion), and a high inoculum level (∼10 CFU/test portion). Data from the study were analyzed according to the Probability of Detection (POD) statistical model as presented in the AOAC validation guidelines.

Results

The dLPODC values with 95% confidence interval for each comparison were; -0.02 (-0.07, 0.03), -0.08 (-0.31, 0.16), and 0.00 (-0.03, 0.03) for the non-inoculated, low, and high contamination levels, respectively.

Conclusions

The dLPODC results demonstrate no difference in performance between the candidate method and reference method for the matrix evaluated.

Highlights

The GENE-UP LMO method demonstrated accuracy and precision in detecting and discerning L. monocytogenes from other Listeria species.
Timing the Implementation of Cultural Practices for Spissistilus festinus (Hemiptera: Membracidae) in California Vineyards Using a Stage-Structured Degree-Day Model
Authors: Bick Emily N , Kron Cindy R , Zalom Frank G
Published: July 2020

The three-cornered alfalfa hopper, Spissistilus festinus (Say), was shown to transmit Grapevine red blotch virus (GRBV), the causative agent for Grapevine red blotch disease, in a greenhouse study on grapes. GRBV is a major concern of wine grape growers due to its economic impact on wine quality. Plants in the family Fabaceae are preferred hosts of S. festinus and are commonly planted as cover crops or present in a vineyard’s native vegetation. In late winter, during grapevine dormancy, S. festinus migrate into vineyards to feed and reproduce on these cover crop and weed hosts. Tilling vineyard floor vegetation provides growers an opportunity to disrupt the life cycle of early instars that are relatively immobile, reducing the S. festinus first-generation population. Nymphal presence is difficult to detect. First through third instars were not detected in sweep net samples in a 2-yr weekly sampling study, whereas fourth and fifth instars were first found on the same sample date as emerging adults. A degree-day model was developed and successfully predicted when early S. festinus instars are present in the vineyard to aid in exploiting the time period when S. festinus is most susceptible to cultural control measures.
Unregulated Algorithmic Trading: Testing the Boundaries of the European Union Algorithmic Trading Regime
Authors: Martins Pereira Clara
Published: July 2020

Trading in modern equity markets has come to be dominated by machines and algorithms. However, there is significant concern over the impact of algorithmic trading on market quality and a number of jurisdictions have moved to address the risks associated with this new type of trading. The European Union has been no exception to this trend.

This article argues that while the European Union algorithmic trading regime is often perceived as a tough response to the challenges inherent in machine trading, it has one crucial shortcoming: it does not regulate the simpler, basic execution algorithms used in automated order routers. Yet the same risk generally associated with algorithmic trading activity also arises, in particular, from the use of these basic execution algorithms—as was made evident by the trading glitch that led to the fall of United States securities trader Knight Capital in 2012. Indeed, such risk could even be amplified by the lack of sophistication of these simpler execution algorithms.

It is thus proposed that the European Union should amend the objective scope of its algorithmic trading regime by expanding the definition of algorithmic trading under the Markets in Financial Instruments Directive (MiFID II) to include all execution algorithms, regardless of their complexity.
Highlights of Veterinary Entomology, 2019
Authors: Pitzer Jimmy B
Published: July 2020

Research in the field of veterinary entomology is dominated by studies concerning arthropods that affect animal health. In 2019, this research primarily addressed the overwhelming industry need to manage detrimental species such as biting flies and ticks and the ongoing problems caused by insecticide/acaricide resistance evolution in these pests. Research also included evidence supporting the need for the conservation of beneficial species, such as biological control organisms. Many studies in a variety of pest systems have demonstrated the potential detrimental effects of insecticide use on nontarget organisms, and those of veterinary importance are no exception. An emphasis also was placed on research regarding alternative management strategies for veterinary pests. The presentation herein provides a descriptive summary of selected research that contributed greatly to the body of knowledge regarding arthropods of veterinary importance. This included several studies that will pave the way towards more effective veterinary pest management in an effort to improve animal health and welfare and, therefore, the sustainability of animal agriculture.
Variability of water supply affected shoot biomass and root depth distribution of four temperate grassland species in monocultures and mixtures
Authors: Haughey Eamon , McElwain Jennifer C , Finn John A
Published: July 2020

Aims

Research on the effects of extreme rainfall events on ecosystem function has primarily focussed on drought or flooding events, which usually include changes to mean or total rainfall, annually or over a season. However, less is known about the effects of increased rainfall variability without change to mean or total amounts. We investigated the effects of increased variation of water supply on shoot and root biomass as well as the distribution of root biomass of four grassland plant species, grown in monoculture and mixture communities.

Methods

Perennial ryegrass (Lolium perenne L., shallow-rooting grass), chicory (Cichorium intybus L., deep-rooting forb), white clover (Trifolium repens L., shallow-rooting legume) and red clover (Trifolium pratense L., deep-rooting legume) were established in mesocosms. Four plants of the same species were grown in monoculture communities and one of each species grown in four-species communities. Water supply was manipulated such that; compared with a baseline level with low variation in water supply, there was a treatment with medium variation (±40%) and another with high variation (±80%). Shoot and root biomass were measured, and vertical root distribution models fitted.

Important Findings

Compared with the low variation treatment, shoot biomass was significantly reduced under high variation for white clover, red clover and four-species communities. Under all conditions, four-species communities produced more shoot and root biomass than predicted by species performance in monoculture (overyielding). Under increased water variation, chicory monocultures allocated a higher proportion of root biomass to deeper soil layers while the total root biomass of white clover monocultures was significantly reduced. These results indicate that increased variability of water supply can negatively affect the shoot and root biomass production of single and multi-species grasslands. There is a need for further investigation of water variation effects on the functioning of multi-species grassland systems at field scale.
Hybrid laparoscopic and open repair of post-nephrectomy flank hernia
Authors: Gan Siang Wei , Bruening Martin , Bhattacharjya Shantanu
Published: July 2020

Surgical repair of flank hernia is not routinely performed, due to perceived technical difficulties with the surgery and risk of recurrence, or the misconception that flank hernia is solely due to a denervation injury. Due to the rareness of flank hernia in the literature, there is no general consensus on the best method of surgical repair. We present the case of a patient with a symptomatic large flank hernia following open nephrectomy, in which a hybrid technique of open and laparoscopic flank hernia repair with sublay mesh and bone anchor fixation was successfully performed with good outcome. This case highlights the benefits of the hybrid approach, which allowed a laparoscopic assessment of the defect and adhesiolysis, followed by the open repair which enabled adequate mesh overlap, fixation to surrounding tissues and bone anchor fixation.
What drives photosynthesis during desiccation? Mosses and other outliers from the photosynthesis–elasticity trade-off
Authors: Perera-Castro Alicia V , Nadal Miquel , Flexas Jaume
Published: July 2020

In vascular plants, more rigid leaves have been linked to lower photosynthetic capacity, associated with low CO2 diffusion across the mesophyll, indirectly resulting in a trade-off between photosynthetic capacity (An) and bulk modulus of elasticity (ε). However, we evaluated mosses, liverworts, and Chara sp., plus some lycophytes and ferns, and found that they behaved as clear outliers of the An–ε relationship. Despite this finding, when vascular and non-vascular plants were plotted together, ε still linearly determined the cessation of net photosynthesis during desiccation both in species with stomata (either actively or hydro-passively regulated) and in species lacking stomata, and regardless of their leaf structure. The latter result challenges our current view of photosynthetic responses to desiccation and/or water stress. Structural features and hydric strategy are discussed as possible explanations for the deviation of these species from the An–ε trade-off, as well as for the general linear dependency between ε and the full cessation of An during desiccation.
Exercise Dose Associated With Military Service: Implications for the Clinical Management of Inherited Risk for Arrhythmogenic Right Ventricular Cardiomyopathy
Authors: Segre Elena M , Hellwig Lydia D , Turner Clesson , Dobson Craig P , Haigney Mark C
Published: July 2020

Introduction

High levels of aerobic exercise in individuals who have a gene mutation associated with arrhythmogenic right ventricular cardiomyopathy (ARVC) are associated with clinical disease progression. Guidelines consequently restrict patients from competitive athletics. However, there is minimal literature to guide the safe dosing of physical activity outside of the setting of competitive athletics. Patients may be physically active pursuant to a variety of careers, including military service. This study aimed to define a therapeutic window for exercise for ARVC gene-positive individuals that are compatible with continuing military service and general health while maintaining a level of exercise below that which risks disease progression.

Materials and Methods

Using standard metabolic equations, we calculated the minimum VO2 max (amount of oxygen utilized at peak exercise capacity) required to pass the physical fitness tests for each branch. We then developed a sample exercise prescription to maintain this level of fitness. We compared the prescribed exercise load with the physical activity levels associated with non-inferior clinical outcomes in ARVC gene-positive individuals. Additionally, we determined the physical activity exposure sustained by service members based on self-report data and compared these values with the upper limit of safe exercise exposure.

Results

Based on a review of the currently available literature, aerobic exercise exposure less than 700 to 1,100 MET-hours/year (metabolic equivalent-hours per year) is not associated with inferior clinical outcomes for gene-positive individuals. A military service member needs 600 to 700 MET-hours/year to minimally pass the physical fitness test. However, many military members are exercising in excess of this minimum, with typical exposures between 900 and 2,400 MET-hours/year.

Conclusions

A therapeutic window of aerobic exercise may exist for ARVC gene-positive individuals which would allow continuation of military service while maintaining levels of exercise restriction associated with non-inferior clinical outcomes.
Is there a spectral turnover in the spin noise of millisecond pulsars?
Authors: Goncharov Boris , Zhu Xing-Jiang , Thrane Eric
Published: July 2020

Pulsar timing arrays provide a unique means to detect nanohertz gravitational waves through long-term measurements of pulse arrival times from an ensemble of millisecond pulsars. After years of observations, some timing array pulsars have been shown to be dominated by low-frequency red noise, including spin noise that might be associated with pulsar rotational irregularities. The power spectral density of pulsar timing red noise is usually modelled with a power law or a power law with a turnover frequency below which the noise power spectrum plateaus. If there is a turnover in the spin noise of millisecond pulsars, residing within the observation band of current and/or future pulsar timing measurements, it may be easier than projected to resolve the gravitational-wave background from supermassive binary black holes. Additionally, the spectral turnover can provide valuable insights on neutron star physics. In the recent study by Melatos and Link, the authors provided a derivation of the model for power spectral density of spin noise from superfluid turbulence in the core of a neutron star, from first principles. The model features a spectral turnover, which depends on the dynamical response time of the superfluid and the steady-state angular velocity lag between the crust and the core of the star. In this work, we search for a spectral turnover in spin noise using the first data release of the International Pulsar Timing Array. Through Bayesian model selection, we find no evidence of a spectral turnover. Our analysis also shows that data from PSRs J1939+2134, J1024–0719, and J1713+0747 prefers the power-law model to the superfluid turbulence model.
Fast-rotating giant stars behind the Coma Berenices star cluster
Authors: Casal Estefanía , Fernández Matilde , Alfaro Emilio J , Casanova Víctor , Tobaruela Ángel
Published: July 2020

In the frame of a study of the empirical isochrones of young stellar clusters, we have carried out BVIc Johnson–Cousins photometry of a sample of K and M stars of the Coma Berenices star cluster. All these stars have known rotational periods. Our main goal is to get a valuable reference on the colour–magnitude diagram, Mv versus B − V, for stars with ages within 400–800 Myr. For this purpose, we obtained BVIc photometry with an average upper limit for the precision of about 0.025 mag and used parallaxes from the Gaia Data Release 2. We found that one-third of our sample is located well above the cluster main sequence and these stars are confirmed as background giants by their radial velocities in the Gaia Data Release 2. This misclassification shows that giants with short-surface rotational periods can mimic main-sequence stars if they are located at the appropriate distance. We recommend caution when using rotational periods in order to determine cluster membership. Besides, the gyrochronology technique should be used only when the luminosity class of the stars is well known. Finally, our cleared sample supports an age of ∼600 Myr for Coma Berenices, rather than an age of ∼800 Myr.
A Conversation between Jacques Bouveresse and Hilary Putnam
Authors: Bouveresse Jacques , Putnam Hilary
Published: July 2020

The following interview took place between Jacques Bouveresse and Hilary Putnam on May 11, 2001 in Paris at the Collège de France. Sandra Laugier was present, preserved the transcription, and proposed that we publish the text here. It was translated into English by Marie Kerguelen Feldblyum LeBlevennec and lightly edited by Jacques Bouveresse, Juliet Floyd, and Sandra Laugier. Themes covered in the interview include the question of Wittgenstein’s importance in contemporary philosophy, Putnam’s development with respect to realism, especially in philosophy of mathematics, and the differences and motivations for realism in mathematics, physics, and ethics. The editors thank Marie Kerguelen Feldblyum LeBlevennec for her translation, and Jacques Bouveresse, Mario De Caro, and Sandra Laugier for permission to publish this transcription.
Neutrophils are key mediators in crescentic glomerulonephritis and targets for new therapeutic approaches
Authors: Antonelou Marilina , Evans Rhys D R , Henderson Scott R , Salama Alan D
Published: July 2020

Crescentic glomerulonephritis (CGN) results from a diverse set of diseases associated with immune dysregulation and the breakdown of self-tolerance to a wide range of autoantigens, some known and some that remain unknown. Experimental data demonstrate that neutrophils have an important role in the pathogenesis of CGN. Upon activation, neutrophils generate reactive oxygen species, release serine proteases and form neutrophil extracellular traps (NETs), all of which can induce direct tissue damage. In addition, serine proteases such as myeloperoxidase and proteinase 3, presented on NETs, can be processed and recognized as autoantigens, leading to the generation and maintenance of autoimmune responses in susceptible individuals. The basis of the specificity of autoimmune responses in different patients to NET proteins is unclear, but relates at least in part to differences in human leucocyte antigen expression. Conditions associated with CGN are often characterized by aberrant neutrophil activation and NETosis and, in some, impaired NET degradation. Targeting neutrophil degranulation and NETosis is now possible using a variety of novel compounds and may provide a promising therapeutic alternative to glucocorticoid use, which has been a mainstay of management in CGN for decades and is associated with significant adverse effects. In this review, we discuss the evidence supporting the role of neutrophils in the development of CGN and the pathways identified in neutrophil degranulation and NETosis that may translate to novel therapeutic applications.
Effects of (−)-epicatechin on mitochondria
Authors: Daussin Frédéric N , Heyman Elsa , Burelle Yan
Published: July 2020

Mitochondrial dysfunction is observed in a broad range of human diseases, including rare genetic disorders and complex acquired pathologies. For this reason, there is increasing interest in identifying safe and effective strategies to mitigate mitochondrial impairments. Natural compounds are widely used for multiple indications, and their broad healing properties suggest that several may improve mitochondrial function. This review focuses on (−)-epicatechin, a monomeric flavanol, and its effects on mitochondria. The review summarizes the available data on the effects of acute and chronic (−)-epicatechin supplementation on mitochondrial function, outlines the potential mechanisms involved in mitochondrial biogenesis induced by (−)-epicatechin supplementation and discusses some future therapeutic applications.
The Adaptation of Pain Assessment Tools from High-Income to Low- and Middle-Income Countries: Psychometric Properties of a Set of Chronic Pain Questionnaires in Mongolian and New Zealand Patient Samples
Authors: Tuck Natalie L , Khuvtsagaan Bayalagmaa , Rashid Usman , Aamir Tipu , Goucke Roger , Regjii Bazarragchaa , Dorjbal Ehkh-Amgalan , Lundeg Ganbold , Bean Debbie J
Published: July 2020

Objective

Chronic pain is a leading cause of disability in low- and middle-income countries; however, pain assessment tools have generally been developed and validated in high-income countries. This study examines the psychometric properties of a set of translated pain (and distress) questionnaires in Mongolia and documents the characteristics of people seeking treatment for chronic pain in Mongolia, compared with those in New Zealand, which is representative of high-income countries.

Design

Cross-sectional, observational.

Setting

Hospital-based pain treatment centers in New Zealand and Mongolia.

Subjects

People seeking treatment for chronic pain in Mongolia (N = 142) and New Zealand (N = 159).

Methods

The Brief Pain Inventory, the Depression Anxiety Stress Scale–21, the Pain Catastrophizing Scale, and the Pain Self-Efficacy Questionnaire were translated into Mongolian and administered to patients attending a hospital-based pain service. Questionnaires that were completed by patients in New Zealand were used for comparisons. Internal reliability, convergent validity, and factor structure were assessed in both groups.

Results

Patients in Mongolia were older and reported lower pain intensity, interference, and distress and higher pain self-efficacy than those in New Zealand. The translated questionnaires had good internal consistencies, and the relationships between pain variables were similar across both groups. The factor structure for the Pain Catastrophizing Scale was consistent across both groups, but this was not the case for the Brief Pain Inventory or the Depression Anxiety Stress Scale–21.

Conclusions

Findings indicate that some pain outcome measures may be appropriate for use in Mongolia and should be investigated in other low- and middle-income countries.
COVID-19 and Mental Health: An Examination of 911 Calls for Service
Authors: Lersch Kim M
Published: July 2020

The purpose of this study was to explore the rate and geographic distribution of 911 calls for service related to mental health issues during the Coronavirus Disease 2019 (COVID-19) pandemic in the City of Detroit, MI, USA. The results suggest that the total number of calls for mental health issues was at the lowest level when compared with the same time period for the previous 3 years. Furthermore, as both the daily reported COVID-19 cases and related deaths increased over time, there was a significant decline in both suicide threats and suicides in progress. Significant hot spots were found for the total calls as well as for threats of suicide. These hot spots did not coincide with the spatial distribution of reported cases of COVID-19 by ZIP code. While higher and lower areas of reported cases were found, these differences by ZIP code were not found to be significant. When compared with the previous 3 years of data, the hot spot area was much smaller in 2020, implying that the mental health-related calls for service were more evenly spread throughout the city.
Association of antimalarial drugs with decreased overall and cause specific mortality in systemic lupus erythematosus
Authors: Jin Ziyi , Wang Fan , Pan Wenyou , Liu Lin , Wu Min , Hu Huaixia , Ding Xiang , Wei Hua , Zou Yaohong , Qian Xian , Wang Meimei , Wu Jian , Tao Juan , Tan Jun , Da Zhanyun , Zhang Miaojia , Li Jing , Feng Xuebing , Sun Lingyun
Published: July 2020

Objective

To evaluate the association and dose–response pattern between antimalarial drugs and overall and cause specific mortality in SLE patients.

Methods

Medical records including information on HCQ/chloroquine (CQ) prescription were extracted from Jiangsu Lupus database. The database was designed to collect data from SLE patients that first-hospitalized during 1999–2009 in Jiangsu province, China, and a follow-up for survival status was performed in 2010 and 2015. Cox and restricted cubic spline models were used to estimate the hazard ratio and 95% CI.

Results

We identified 221 deaths among 2446 SLE patients in total. Compared with non-users, decreased overall mortality was associated with either HCQ or CQ users, with adjusted hazard ratio (95% CI) of 0.49 (0.35, 0.67) and 0.49 (0.27, 0.87), respectively. The association between HCQ/CQ and overall mortality was similar across subgroups, such as patients with comorbidities and organ involvements. Interestingly, both the time and the daily dosage of HCQ/CQ use were related to decreased mortality of SLE in a linear dose–response relationship. In cause specific analyses, HCQ/CQ was inversely associated with death from renal insufficiency and other organ (cardiopulmonary, gastrointestinal and haematological) involvements, with adjusted hazard ratio (95% CI) of 0.23 (0.09, 0.55) and 0.25 (0.10, 0.62), respectively, yet it was not significantly associated with mortality from infection and neuropsychiatric involvements.

Conclusion

Antimalarial drugs were associated with lower risk of SLE mortality, especially renal insufficiency- and other organ involvement-related death. The protective effects for survival might be augmented by adherence and full dosage of these drugs.
Relaxed Random Walks at Scale
Authors: Fisher Alexander A , Ji Xiang , Zhang Zhenyu , Lemey Philippe , Suchard Marc A
Published: July 2020

Relaxed random walk (RRW) models of trait evolution introduce branch-specific rate multipliers to modulate the variance of a standard Brownian diffusion process along a phylogeny and more accurately model overdispersed biological data. Increased taxonomic sampling challenges inference under RRWs as the number of unknown parameters grows with the number of taxa. To solve this problem, we present a scalable method to efficiently fit RRWs and infer this branch-specific variation in a Bayesian framework. We develop a Hamiltonian Monte Carlo (HMC) sampler to approximate the high-dimensional, correlated posterior that exploits a closed-form evaluation of the gradient of the trait data log-likelihood with respect to all branch-rate multipliers simultaneously. Our gradient calculation achieves computational complexity that scales only linearly with the number of taxa under study. We compare the efficiency of our HMC sampler to the previously standard univariable Metropolis–Hastings approach while studying the spatial emergence of the West Nile virus in North America in the early 2000s. Our method achieves at least a 6-fold speed increase over the univariable approach. Additionally, we demonstrate the scalability of our method by applying the RRW to study the correlation between five mammalian life history traits in a phylogenetic tree with $3650$ tips.[Bayesian inference; BEAST; Hamiltonian Monte Carlo; life history; phylodynamics, relaxed random walk.]
Stakeholders’ Perspective for Improved Universal Newborn Hearing Screening Uptake in Odisha, India
Authors: Sahoo Krushna Chandra , Dwivedi Rinshu , Athe Ramesh , Bhattacharya Debdutta , Rajsekhar Kavitha , Pati Sanghamitra
Published: July 2020

abstract

Universal Newborn Hearing Screening (UNHS) is a significant public health initiative as early diagnosis and intervention are critical for children’s cognitive development. In India, priority for UNHS has been provided since 2013; however, there are various operational challenges associated with it. There is a lack of multi-stakeholders perspective on UNHS, which is crucial for improving the service intake. Therefore, this study attempted to understand the perspective of various stakeholders to explore the practices, processes and technologies used in the existing UNHS landscape in Odisha, India. The qualitative in-depth interviews were conducted among various stakeholders including 15 mothers, 5 service providers (audiologists), 10 districts and state-level programme managers. Data were analysed using content analysis approaches. Two major themes emerged were ‘social-shaping of technology for UNHS’ and ‘mothers’ understanding and experience on UNHS’. Employee retention, equipment limitations, facilities maintenance and little knowledge among mothers about hearing screening have been described as major operational challenges. The study revealed that to increase universal coverage ‘screening technology should be socially shaped’. There seems to be a need for ‘portable technology with ease to use and better diagnostic accuracy’ for first-stage screening at various levels of healthcare facilities along with community literacy on UNHS.
‘Re-constituting’ the Internal Market: Towards a Common Law of International Trade?*
Authors: Schütze Robert
Published: July 2020

Are the trade philosophies behind the EU internal market and the WTO international market converging or diverging; and are we, or are we not, moving towards a ‘common law of international trade’? Twenty years ago, an interesting—and swiftly famous—answer to this question was given by Joseph H.H. Weiler. Studying the ‘constitution of the common market’, the historical evolution of free movement law is here divided into five periods or generations. The underlying Weiler thesis is thereby as simple as it is beautiful: starting with an early radical philosophy in Dassonville, the European Union has gradually and consistently moved away from its original hyper-liberal approach towards an ever more deferential approach; and the transformation of Article 34 TFEU into a discrimination format ultimately leads to a convergence with international law. What are the empirical and normative credentials of this stylised construction of the internal market? This article argues that there are fundamental shortcomings in this standard interpretation of the evolution of the internal market, and that a historical reconstruction arrives at a very different empirical and normative picture. What can this ‘revisionist’ result mean for EU law scholarship in general? If EU constitutionalism wishes to ‘re-constitute’ its object of study properly, it needs to abandon the abstract ways of philosophizing that have become commonplace in the last 25 years. Part and parcel of this methodological renaissance must be a renewed commitment to test (constitutional) theory against (judicial) practice.
Incidence of squamous cell carcinomas of the head and neck following prolonged pegylated liposomal doxorubicin
Authors: Rose Peter G. , Fu Frances , Chambers Laura M. , Mei Lin , De Bernardo Robert , Prendes Brandon L. , Lamarre Eric
Published: July 2020

Despite numerous case reports, the incidence of a secondary diagnosis of head and neck squamous cell carcinoma (HNC) following pegylated liposomal doxorubicin (PLD) treatment is unknown. Computerized pharmacy records were searched at a large, multi-center healthcare system for patients who received PLD. Electronic medical records were searched to identify the patient’s age at treatment initiation of PLD, diagnosis for which they were treated with PLD, number of courses and total cumulative dose of PLD (TCDPLD) and secondary malignancies. Published PLD associated HNC was utilized to determine the lowest and median TCDPLD doses associated with HNC. One thousand two hundred ninety eligible patients who had been treated with PLD were identified. The lowest TCDPLD associated HNC in the literature is 405 mg/m2. In our healthcare system, 275 patients received more than 400 mg/m2 yielding a risk of 0.004%. One hundred fifty-one patients received the lowest TCDPLD associated with HNC cancer in our series which was 640 mg/m2 yielding a risk of 0.007%. Four of 30 patients (13.3%) developed HNC who received the median TCDPLD associated with HNC in the literature of 1440 mg/m2. Five of 20 patients (25%) receiving 1650 mg/m2 developed HNC in our healthcare system. Prolonged therapy with PLD is associated with an increased risk of HNC. This risk appears to be related to the cumulative dose varying from 0.004 to 13.3% at the lowest and median TCDPLD of reported cases in the literature, respectively. Oncologists need to be aware of this risk and to screen patients appropriately.
Stress Hyperglycemia and Mortality in Subjects With Diabetes and Sepsis
Authors: Fabbri Andrea , Marchesini Giulio , Benazzi Barbara , Morelli Alice , Montesi Danilo , Bini Cesare , Rizzo Stefano Giovanni
Published: July 2020

Objectives:

Poor glycemic control is associated with mortality in critical patients with diabetes. The aim of the study was to assess the predicting value of stress hyperglycemia in patients with diabetes following hospital admission for sepsis.

Design:

Retrospective observational study.

Setting:

Adult, emergency department, and critical care in a district hospital.

Patients:

In a 10-year retrospective analysis of sepsis-related hospitalizations in the emergency department, we carried out a secondary analysis of 915 patients with diabetes (males, 54.0%) in whom both fasting glucose at entry and glycosylated hemoglobin were available.

Interventions:

None.

Measurements and Main Results:

Patients’ mean age was 79.0 (sd 11.0), glucose at admission was 174.0 mg/dL (74.3 mg/dL), and glycosylated hemoglobin was 7.7% (1.7%). Stress hyperglycemia was defined by the stress hyperglycemia ratio, that is, fasting glucose concentration at admission divided by the estimated average glucose derived from glycosylated hemoglobin. A total of 305 patients died (33.3%) in hospital. Factors associated with in-hospital case fatality rate were tested by multivariable logistic model. Ten variables predicting outcomes in the general population were confirmed in the presence of diabetes (male sex, older age, number of organ dysfunction diagnoses, in particular cardiovascular dysfunction, infection/parasitic, circulatory, respiratory, digestive diseases diagnosis, and Charlson Comorbidity Index). In addition, also glycemic control (glycosylated hemoglobin: odds ratio, 1.17; 95% CI, 1.15–1.40) and stress hyperglycemia (stress hyperglycemia ratio: 5.25; 3.62–7.63) were significant case fatality rate predictors. High stress hyperglycemia ratio (≥ 1.14) significantly increased the discriminant capacity (area under the receiver operating characteristic curve, 0.864; se, 0.013; p < 0.001).

Conclusions:

Stress hyperglycemia, even in the presence of diabetes, is predictive of mortality following admission for sepsis. Stress hyperglycemia ratio may be used to refine prediction of an unfavorable outcome.
Ocular Adverse Effects of Amiodarone: A Systematic Review of Case Reports
Authors: Alshehri Mona , Joury Abdulaziz
Published: July 2020

SIGNIFICANCE

Amiodarone is an excellent antiarrhythmic medication; however, it has numerous systemic and ocular adverse effects.

PURPOSE

We aimed to improve our understanding of amiodarone and its ocular adverse effects by performing a systematic review and meta-analysis of published case reports.

METHODS

This systematic review was reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. We used the MEDLINE database, primarily through PubMed, and used keywords (amiodarone, eye, eye diseases, visual/ocular adverse effects/manifestations) to identify case reports of ocular adverse effects after amiodarone use. The initial search resulted in 92 total case reports. However, after excluding nonrelevant case reports, 25 cases were selected for the final analysis.

RESULTS

Among the patients in the 25 case reports, 18 were male (72%), and the median age was 66 ± 9.9 years. In 15 cases (60%), the patients reported halos around light and/or decrease in vision after amiodarone use. The most common ophthalmic examination findings were cornea verticillata/vortex keratopathy in 19 cases (76%), followed by different patterns of papilledema and retinal hemorrhages in 5 cases (20%). Discontinuation of amiodarone was the most common intervention, followed by application of topical heparin. Outcomes among case reports were variable.

CONCLUSIONS

Cornea verticillata/vortex keratopathy was the most common ocular adverse effect in cases where amiodarone was administered. Early recognition of amiodarone-induced ocular adverse effects is imperative to prevent worsening keratopathy or uncommon adverse effects. Collaboration between physicians prescribing amiodarone—to recognize the ocular symptoms—and referral to eye care physicians are important.
Abdominal Organs Attenuation Values and Abdominal Aortic Calcifications on Virtual and True Noncontrast Images Obtained With Third-Generation Dual-Source Dual-Energy Computed Tomography
Authors: Kim Sungmin , Kang Byeong Seong , Kwon Woon-Jung , Bang Minseo , Lim Soyeoun , Park Gyeong Min , Lee Tae Young
Published: July 2020

Purpose

To evaluate the agreement and correlation between attenuation values and vascular calcification volume for intra-abdominal structures from true noncontrast (TNC) images and those from virtual noncontrast (VNC) images obtained by dual-source dual-energy computed tomography (CT) using a quadriphasic dynamic protocol.

Methods

Seventy-six patients who underwent quadriphasic abdominal CT were retrospectively reviewed. An arterial, portal venous, and 5-minute delayed phase postcontrast series was obtained using dual-source dual-energy CT. Virtual noncontrast images were processed from the arterial, portal venous, and 5-minute delayed phase series. Attenuation values for the liver, pancreas, kidneys, muscle, fat, vertebra, gallbladder, aorta, inferior vena cava, portal vein, and aortic calcification volumes were recorded. Attenuation values for the liver, pancreas, vertebra, and muscle obtained from VNC were adjusted using linear regression.

Results

Repeated-measures analysis of variance and Bonferroni multiple-comparison post hoc correction revealed significant differences between TNC and VNC attenuation values for the organs. There was an excellent correlation between the TNC and VNC attenuation values for the liver, pancreas, muscle, vertebra, and fat. The calcification volume was significantly smaller on VNC than on TNC. The adjusted attenuation values estimated by regression equations afforded better approximation.

Conclusions

Abdominal VNC images obtained with third-generation dual-source dual-energy CT cannot replace TNC images without adjustment of the attenuation values.
Magnetic Resonance Imaging Findings of Crystalloid-Containing Parotid Cysts
Authors: Alavanja Aleksandar , Parker Kyle , Ginat Daniel Thomas
Published: July 2020

Crystalloids are occasionally encountered on fine needle aspiration of cystic parotid lesions. This goal of this study was to retrospectively characterize the MRI features of a series benign crystalloid-containing parotid cysts. A total of 4 patients with fine needle aspiration findings of crystalloids and available parotid MRI scans were identified. Review of the imaging revealed that the cystic lesions contain layering material that corresponds to crystals.