Additional Tests Research Articles

Combinatorial prediction of therapeutic perturbations using causally-inspired neural networks.

As an alternative to target-driven drug discovery, phenotype-driven approaches identify compounds that counteract the overall disease effects by analyzing phenotypic signatures. Our study introduces a novel approach to this field, aiming to expand the search space for new therapeutic agents. We introduce PDGrapher, a causally-inspired graph neural network (GNN) designed to predict combinatorial perturbagens - sets of therapeutic targets - capable of reversing disease effects. Unlike methods that learn responses to perturbations, PDGrapher solves the inverse problem, which is to infer the perturbagens necessary to achieve a specific response - i.e., directly predicting perturbagens by learning which perturbations elicit a desired response. By encoding gene regulatory networks or protein-protein interactions, PDGrapher can predict unseen chemical or genetic perturbagens, aiding in the discovery of novel drugs or therapeutic targets. Experiments across nine cell lines with chemical perturbations show that PDGrapher successfully predicted effective perturbagens in up to 13.33% additional test samples and ranked therapeutic targets up to 35% higher than the competing methods, and the method shows competitive performance across ten genetic perturbation datasets. A key innovation of PDGrapher is its direct prediction capability, which contrasts with the indirect, computationally intensive models traditionally used in phenotype-driven drug discovery that only predict changes in phenotypes due to perturbations. The direct approach enables PDGrapher to train up to 25 times faster than methods like scGEN and CellOT, representing a considerable leap in efficiency. Our results suggest that PDGrapher can advance phenotype-driven drug discovery, offering a fast and comprehensive approach to identifying therapeutically useful perturbations.

Mendelian randomization analysis of psoriasis and psoriatic arthritis associated with risks of ulcerative colitis.

This study is designed to explore the potential causal relationship between psoriasis and psoriatic arthritis (PsA) while investigating the genetic basis shared by these inflammatory diseases. Significant single nucleotide polymorphisms (SNPs) associated with UC, psoriasis, and PsA were selected as genetic instrumental variables using Genome-Wide Association Study (GWAS) datasets. Additionally, Mendelian randomization (MR) methods, including inverse-variance weighting (IVW), MR-Egger regression, and Weighted Median (WME), were utilized to evaluate the causal relationships between these diseases. Moreover, sensitivity analysis and heterogeneity testing were conducted to validate the stability of the results. A total of 123 significant SNPs associated with psoriasis, PsA, and UC were identified as genetic instrumental variables based on GWAS datasets. The analysis revealed a 36% increased risk of UC with psoriasis (odds ratio [OR]=1.350, 95% confidence interval [CI]=1.065-1.729, P=0.012) and a 32.9% increased risk of UC with PsA (OR=1.329, 95% CI=1.176-1.592, P<0.001). Further analysis showed a 43.5% increased risk of psoriasis with UC (OR=1.435, 95% CI=1.274-1.831, P<0.001) and a 45.8% increased risk of PsA with UC (OR=1.458, 95% CI=1.166-1.822, P=0.0013). In addition, sensitivity analysis and heterogeneity testing demonstrated the high stability of these results. Particularly, neither MR-Egger regression analysis nor leave-one-out analysis revealed significant heterogeneity or pleiotropy bias, indicating the reliability of these causal estimates. Moreover, the use of the MR-PRESSO further confirmed the positive correlation between psoriasis and UC, and the corrected estimates remained consistent with IVW analysis results after excluding potential outlier SNPs, enhancing the credibility of the analysis. This study strengthens the understanding of the genetic and causal relationships among UC, psoriasis, and PsA through GWAS and MR methods, revealing the genetic basis they may share. These findings not only provide a novel perspective on the comorbidity mechanisms of these diseases but also offer a valuable reference for the development of future treatment strategies and intervention measures.

Triphenylamine based oxime ester photoinitiator for LED-induced free radical photopolymerization and 3D printing

With the development of light-emitting diode (LED), it is increasingly important to design and prepare photoinitiators that can be used for LED excitation. We designed and synthesized four new LED oxime ester photoinitiators (TOXEs) based on the triphenylamine group. Among them, the maximum absorption wavelengths of TOXE-3 and TOXE-4 are red-shifted to 402 nm and 397 nm, and have high molar absorption coefficients (ε) of 24315 M-1cm−1 and 29915 M-1cm−1, respectively, which are higher than that of ethenone, 1-[9-ethyl-6-(2-methylbenzoyl)-9H-carbazol-3-yl] ethanone 1-(O-acetyloxime) (OXE02, 342 nm, 21836 M-1cm−1), indicating that it can be used in LED polymerization. Investigating the photopolymerization properties of the TOXEs/α, ω-diacryloyl poly(ethylene glycol) (PEGDA) system, under LED@365 nm irradiation, the double bond conversion rate (DC) of TOXE-1 and TOXE-2 were 83 % and 92 %, which were higher than OXE02 (80 %). Under LED@405 nm irradiation, the DC of TOXE-3 and TOXE-4 are 80 % and 78 % respectively, which is higher than that of OXE02 (52 %). To improve the photoinitiation ability of TOXEs, a two-component photoinitiation system using bis(4-tert-butylphenyl) iodonium (Iod) as an additive was tested. The DC of TOXEs has been improved under different light sources. Under LED@480 nm irradiation, the final DC of TOXE-4/Iod/PEGDA is 83 %. In addition, TOXE-3 and TOXE-4 can be applied to the laser cladding deposition (LCD) 3D printers. At the same time, we conduct research and verification on the polymerization mechanism of TOXEs through steady-state photolysis and electron spin resonance spin trapping experiments (ESR-ST). In addition, cytotoxicity assay and thermal stability testing showed that TOXEs exhibited excellent biocompatibility and thermal stability.

Postpartum Excessive Social Support Scale: A Scale Development and Psychometric Testing Study.

In Turkey and other collectivist cultures, child-rearing is a communal effort provided by multiple family members, especially female relatives such as mothers-in-law, aunts, and sisters. Environments with excessively controlling social factors can adversely affect their maternal roles. This study was conducted to develop a measurement tool for determining postpartum excessive social support. This is a scale development and psychometric evaluation study. In the study, a draft of the Postpartum Excessive Social Support Scale (PESSS) was created, subsequently submitted to expert opinion, and administered to mothers in the postpartum period of 1 to 6 weeks online between March and December 2023 (n = 440). A factor analysis (including explanatory factor analysis [EFA] and confirmatory factor analysis) was conducted to determine the construct validity of the scale, while Cronbach's alpha was examined to establish its reliability. Response bias (Hotelling T2) and additivity (Tukey's test of additivity) of the scale were also determined in the study. For the content validity of the scale, 10 experts from the field of midwifery were consulted (content validity index [CVI] = 0.80). As a result of the EFA, Kaiser-Meyer-Olkin value was found as 0.916. Through factor analysis using the direct oblimin rotation technique, a four-factor structure was identified for the scale, explaining 64.197% of the total variance (social pressure, effect of environmental factors on paternal role, effect of environmental factors on maternal role, and barriers in mother-infant interaction). The internal reliability coefficient of the scale was highly reliable (Cronbach's alpha = 0.936). There was no response bias in the scale (Hotelling's T2 = 433.558, p < .001) and it was additive (Tukey's Non-additivity = 0.000, p < .001). The PESSS is a 20-item scale measuring excessive social support between 1 and 6 weeks postpartum. The PESSS serves as a guiding tool for health care professionals to identify excessive environmental pressure hindering mothers' maternal role and to provide care accordingly. In this context, health care professionals can readily utilize the PESSS in routine postpartum assessments for mothers.

Three-Direction Fusion for Accurate Volumetric Liver and Tumor Segmentation.

Biomedical image segmentation of organs, tissues and lesions has gained increasing attention in clinical treatment planning and navigation, which involves the exploration of two-dimensional (2D) and three-dimensional (3D) contexts in the biomedical image. Compared to 2D methods, 3D methods pay more attention to inter-slice correlations, which offer additional spatial information for image segmentation. An organ or tumor has a 3D structure that can be observed from three directions. Previous studies focus only on the vertical axis, limiting the understanding of the relationship between a tumor and its surrounding tissues. Important information can also be obtained from sagittal and coronal axes. Therefore, spatial information of organs and tumors can be obtained from three directions, i.e. the sagittal, coronal and vertical axes, to understand better the invasion depth of tumor and its relationship with the surrounding tissues. Moreover, the edges of organs and tumors in biomedical image may be blurred. To address these problems, we propose a three-direction fusion volumetric segmentation (TFVS) model for segmenting 3D biomedical images from three perspectives in sagittal, coronal and transverse planes, respectively. We use the dataset of the liver task provided by the Medical Segmentation Decathlon challenge to train our model. The TFVS method demonstrates a competitive performance on the 3D-IRCADB dataset. In addition, the t-test and Wilcoxon signed-rank test are also performed to show the statistical significance of the improvement by the proposed method as compared with the baseline methods. The proposed method is expected to be beneficial in guiding and facilitating clinical diagnosis and treatment.

Biliary Duct Dilatation: AJR Expert Panel Narrative Review.

Biliary duct dilatation is a common incidental finding in practice, but it is unlikely to indicate biliary obstruction in the absence of clinical symptoms or elevated levels on liver function tests (LFTs). However, the clinical presentation may be nonspecific, and LFTs may either be unavailable or difficult to interpret. The goal of this AJR Expert Panel Narrative Review is to highlight a series of topics fundamental to the management of biliary duct dilatation, providing consensus recommendations in a question-and-answer format. We start by covering a basic approach to interpreting LFT results, the strengths and weaknesses of the biliary imaging modalities, and how and where to measure the extrahepatic bile duct. Next, we define the criteria for biliary duct dilatation, including patients with prior cholecystectomy and advanced age, and discuss when and whether biliary duct dilatation can be attributed to papillary stenosis or sphincter of Oddi dysfunction. Subsequently, we discuss two conditions in which the duct is pathologically dilated but not obstructed: congenital cystic dilatation (i.e., choledochal cyst) and intraductal papillary neoplasm of the bile duct. Finally, we provide guidance regarding when to recommend obtaining additional imaging or testing, such as endoscopic ultrasound or ERCP, and include a discussion of future directions in biliary imaging.

Comprehensive Genomic Testing: Tissue Stewardship and Best Practices

Biomarker-driven targeted therapies have shaped the oncology treatment landscape for patients with advanced solid tumors over the past decade. Comprehensive genomic profiling (CGP) has played a key role in precision medicine as it enables simultaneous identification of multiple biomarkers to guide cancer diagnosis, therapy selection, and prognostication. As a result, tissue stewardship for successful CGP testing is paramount. In addition, widespread adoption of less invasive sampling techniques leaves less diagnostic tissue for additional or future testing as smaller biopsies are acquired. To help oncology care practitioners overcome these challenges, this paper provides an overview of current genomic testing methodologies and offers guidelines on best practices for tissue stewardship and preanalytic practices for successful CGP testing and efficient turnaround times for laboratory tests.

Dicationic imidazole ionic liquid stationary phase for preservative detection and its application under mixed mode of HILIC/RPLC/IEC

BackgroundFood safety has always been a great concern, and the detection of additives is vital to ensuring food safety. Therefore, there is a necessity to develop a method that can quickly and efficiently separate and detect additives in food. High performance liquid chromatography is widely used in the analysis and testing of food additives. Ionic liquids have attracted wide attention in the preparation of high performance liquid chromatography stationary phases owing to their high stability, low vapor pressure and adjustable structure. ResultsWe developed a novel dicationic imidazole ionic liquid stationary phase for the simultaneous determination of organic preservatives (sodium benzoate, potassium sorbate) and inorganic preservatives (nitrate and nitrite) in foodstuffs under mixed-mode chromatography. The method had the advantages of easy operation, high reproducibility, good linearity and precision. In the detection of these four preservatives, the limit of detection ≤0.4740 mg⋅L−1 and the limit of quantification ≤1.5800 mg⋅L−1. The intra-day and inter-day precision were less than 4.02%, and the recovery rate was 95.90∼100.19 %. At the same time, we also characterized the stationary phase, explored the mechanism and evaluated the chromatographic performance. The stationary phase was able to operate under the mixed mode of reversed phase/hydrophilic interaction/ion exchange chromatography, and it was capable of separating hydrophilic substances, hydrophobic substances, acids, and inorganic anionic substances with good separation efficiency and had high column efficiency. SignificanceIn summary, the stationary phase has a promising application in the routine analysis of organic and inorganic preservatives in food. In addition, the stationary phase has good separation ability for hydrophilic, hydrophobic, ionic substances and complex samples, making it a prospective material for chromatographic separation.

Barium titanate write-once read-many times resistive memory with an ultra-high on/off current ratio of 108

Write-once read-many times (WORM) resistive memories fabricated using perovskite barium titanate (BaTiO3, BTO) resistive switching (RS) layer are demonstrated in this study. The BTO RS layers with thicknesses of 3.2–8.5 nm are fabricated by radio frequency sputtering at room temperature. Annealing processes at 400–600 °C are used to modify the oxygen vacancy content in the BTO layer and thereby control the OFF-state current of an Al/BTO/n+-Si WORM device. The ION/IOFF ratio increases with increasing annealing temperature until 500 °C. A negative effect is observed when the temperature further rises to 600 °C. The optimal Al/BTO/n+-Si device shows an ultra-high ION/IOFF ratio of 108 and a low coefficient of variation of 6% for set voltages. The writing speed is 80 ns and the power consumption is 400 pJ. In addition, retention and stress tests are performed to confirm high data storage reliability of the device. Mechanisms for voltage-polarity independent writing process and the related energy band diagrams are explored.

The Role of Surveillance in Predicting Fracture in Pediatric Patients With Incidentally Discovered Nonossifying Fibromas and Fibrous Cortical Defects: Is It Worth It?

Nonossifying fibroma (NOF) and fibrous cortical defect (FCDs), the most common benign pediatric bone lesions, are usually incidental x-ray findings. Surveillance of characteristic lesions has been recommended to monitor for enlargement and assess fracture risk. However, no accepted fracture risk prediction guidelines exist, so indications for prophylactic surgery are unclear. The study's purposes were to (1) characterize the timing of NOF/FCD-associated fractures, (2) quantify the resources devoted to surveillance, and (3) evaluate the potential for surveillance to prevent pathologic fracture. A single institution retrospective review was conducted to identify pediatric patients (below 18y old) with clinical-radiographic documentation of an NOF or FCD diagnosis from 2012 to 2020. Patients who presented with fracture were tallied but excluded from the surveillance analysis. Patients without at least one follow-up visit were also excluded. Lesional radiographic features were characterized on initial imaging. The number of visits and imaging studies devoted to surveillance were tabulated. The number of fractures and prophylactic surgeries were recorded to quantify the potential of surveillance to prevent pathologic fractures. The study population presenting without fracture consisted of 301 patients with 364 lesions with a mean follow-up of 20 months. By contrast, over the same period, 38 patients presented with NOF/FCD associated pathologic fractures. Surveillance included 1037 additional imaging tests over 1311 follow-up visits, or on average, 3.4 imaging studies and 4.4 visits per patient. During surveillance, only 2 (0.55%) lesions fractured. Another 10/364 (2.8%) patients underwent curettage and grafting, suggesting that-at best-the potential for preventing pathologic fracture by surveillance, assuming all 10 patients who underwent surgery would have subsequently fractured along with the 2 documented fractures, is 3.3% of lesions (12/364). The small number of fractures and surgeries during the follow-up period probably does not justify additional resources for surveillance beyond the initial visit, except in symptomatic patients with large lesions. However, subsequent visits may play a role in educating patients and their families regarding the natural history of these lesions. Prognostic Level II-retrospective study.

Modes of assay interference and the effectiveness of serum pretreatment approaches in detection of anti-HLA antibodies

AimsSeveral modes of assay interference common to immunoassays affect solid-phase single-antigen bead-based immunoassays (SAB) used to detect antibodies against human leucocyte antigens (HLA). Best practice recommendations include methods to address...

Analysis of Planetary Scale Waves Using Idealized Sudden Stratospheric Warming Simulations in Different Dynamical Cores

AbstractPlanetary waves from the troposphere are known to play an important role in sudden stratospheric warming (SSW). To evaluate the representation of large‐scale waves in idealized SSW simulations, three dynamical cores of the National Center for Atmospheric Research Community Atmosphere Model were tested in this study: the Eulerian (EUL) spectral‐transform, finite‐volume (FV), and spectral element (SE) models. Notable differences were observed among the dynamical cores, with FV being unable to generate major SSWs and simulating minor SSWs less effectively than the other models. Wave decomposition analysis revealed distinct planetary wave propagation patterns during the development of each event. Zonal Wave Number 2 wave activities primarily determined SSW types, and ZWN1 led SSWs to recovery during the ensuing periods. However, FV failed to adequately propagate large‐scale waves in minor SSW events, preventing the reversal of stratospheric zonal‐mean zonal winds. Interestingly, FV showed decreased upward Eliassen–Palm flux compared to that of other dynamical cores, even during climatology. Additional tests were performed to examine the reasons for FV's atypical results, but the dynamic impacts on planetary waves remain poorly understood.

Classification of optical coherence tomography images using deep machine learning methods

Backgraund. Optical coherence tomography (OCT) is a modern high-tech and informative method for detecting pathology of the retina and preretinal layers of the vitreous body. However, the description and interpretation of the research results require high qualifications and special training of an ophthalmologist, and significant time expenditure for the doctor and the patient. At the same time, the use of mathematical models based on artificial neural networks (ANN- models) currently makes it possible to automate many processes associated with image processing. Therefore, solving problems associated with automating the process of classifying OCT images based on ANN models is actual.&#x0D; Aims. To develop architectures of mathematical (computer) models based on deep learning of convolutional neural networks (CNN) for classification of OCT images of the retina. To compare the results of computational experiments conducted using Python tools in the Google Colaboratory with single-model and multi-model approaches and evaluate classification accuracy. To make conclusions about the optimal architecture of ANN models and the values of the hyperparameters used.&#x0D; Materials and methods. The original dataset, which was anonymized OCT images of real patients, included more than 2000 images obtained directly from the device in a resolution of 1920 × 969 × 24 BPP. The number of image classes is 12. To create the training and validation data sets, a subject area of 1100 × 550 × 24 BPP was “cut out.” Various approaches were studied: the possibility of using pretrained CNNs with transfer learning, techniques for resizing and augmenting images, as well as various combinations of hyperparameters of ANN-models. When compiling the model, the following parameters were used: Adam optimizer, categorical_crossentropy loss function, accuracy metric. All technological processes with images and ANN-models were carried out using Python language tools in Google Colaboratory.&#x0D; Results. Single-model and multi-model principles for classifying OCT images of the retina are proposed. Computational experiments on automated classification of such images obtained from a DRI OCT Triton 3D tomograph using various ANN model architectures showed an accuracy of 98-100% during training and validation and 85% during an additional test, which is a satisfactory result. The optimal architecture of the ANN model - a six-layer convolutional network - was selected and the values of its hyperparameters were determined.&#x0D; Conclusions. The results of deep training of convolutional neural network models with various architectures, their validation and testing showed satisfactory classification accuracy of retinal OCT images. These developments can be used in decision support systems in the field of ophthalmology.

Evaluating different rates of activated carbon in commercially produced seed coatings in laboratory and field trials

Pre‐emergent herbicides, commonly employed for managing invasive annual plants, often fail to meet restoration targets due to the absence of remnant perennial plants, which leaves sites vulnerable to re‐invasion and hinders effective control of annual grasses. Combining an herbicide treatment with seeding is therefore desirable, but seeded plants can also be negatively impacted by pre‐emergent herbicides. Herbicide protection (HP) seed technologies use activated carbon to adsorb herbicide near seeds and have shown promise for allowing simultaneous deployment of herbicide and seed, but recent research recommends numerous additional refinements be tested. We addressed some of these recommendations through one laboratory and a field trial replicated at multiple sites to explore whether commercially produced, single‐seed HP coatings with two different rates of activated carbon can prevent herbicide‐related damage to two perennial bunchgrasses native to the western United States. We also investigated how these coated prototypes compare in performance to the multi‐seed extruded herbicide protection pellets (HPPs) tested in prior research. In the laboratory, neither coating treatment reduced total emergence, emergence rate, survival, or biomass in the absence of herbicide. In the presence of herbicide, both provided several‐fold higher survival and aboveground biomass compared to untreated bare seed, but this represented incomplete protection from herbicide. In field trials where conditions were harsher than the laboratory, we found no evidence of HP from any treatment, and HPPs reduced seedling count for one species. We conclude that the tested HP coating prototype is an improvement over HPPs but requires additional refinements and testing.

Potential Nephrotoxicity of Combination of Vancomycin and Piperacillin-Tazobactam: Recommendations from the AG ABS of the DGPI supported by experts of the GPN

The combination of vancomycin and piperacillin/tazobactam (V+P/T) is used for empirical antibiotic treatment of severe infections, especially in immunocompromised patients and those colonized with multidrug-resistant bacteria. Nephrotoxicity is a frequently observed adverse effect of vancomycin. Its risk can be reduced by therapeutic drug monitoring and adjusted dosing. Piperacillin/tazobactam (P/T) rarely causes interstitial nephritis. The results of retrospective cohort studies in children predominantly show a low, clinically irrelevant, additive nephrotoxicity (defined as an increase in creatinine in the serum) of both substances. Due to the limitations of the existing publications, the ABS working group of the DGPI and experts of the GPN do not recommend against the use of P/T plus vancomycin. Preclinical studies and a prospective study with adult patients, which evaluated different renal function tests as well as clinical outcomes, do not support previous findings of additive nephrotoxicity. Time-restricted use of V+P/T can minimize exposure and the potential risk of nephrotoxicity. Local guidelines, developed in collaboration with the antibiotic stewardship team, should define the indications for empirical and targeted use of P/T and V+P/T. When using combination therapy with V+P/T, kidney function should be monitored through clinical parameters (volume status, balancing, blood pressure) as well as additional laboratory tests such as serum creatinine and cystatin C.

Interconnect Stress Testing as a Tool for Assessment of Reliability of Modern PCBs

The of miniaturization can be seen in electronics for some time already. The pinout of active components grows enabling them to have additional functions. The trend in usage of System in a Package (SiP) solutions is also evident thus routing of the active and passive elements became also challenging. To overcome this challenge boards with High Density Interconnection (HDI) where not only through hole, but also different kinds of microvias e.g. blind, buried, stacked, staggered via are used. The standard procedure to test reliability of boards and assemblies is very resource-hungry especially in time and money, as the tests have to be carried out in climatic chambers which lasts for weeks, followed by additional destructive testing like cross-sections. On the other hand IST (Interconnect Stress Testing) is a quick test, that enables to have assessment of the used technology especially the quality of the through holes of all types. Although the coupons are destroyed during the test, it is not necessary to test the manufactured circuits. This saves both materials and time. The technology optimizations and the key findings will be presented within the paper.

OS TESTES SITUACIONAIS DE INTELIGÊNCIA EMOCIONAL COMO UM TESTE ADAPTATIVO COMPUTADORIZADO

The present study aimed to assess whether an emotional understanding test (STEU) and an emotional management test (STEM) could benefit from being administered as computer-adaptive tests (CATs) without impacting the validity of the test scores. To this end, 11 item selection algorithms (ISAs) were benchmarked for their bias and efficiency. Two simulation studies were run using the same response patterns from the 688 participants used in the original validation study, the same 11 ISAs, but differed in their stopping rules (SRs). For the first study, one simulation was run for each ISA with the SR being standard error lower than (ΔSE &lt; ), the most commonly used stopping rule criterion. For the second study, k simulations were run for each ISA, for each test, with the SR being a fixed number of items between 1 and k, where k was the total number of items of the relevant test (32 for the STEU and 30 for the STEM). Results of the first simulation showed that testing with all ISAs resulted in accurate ability estimates, all of them having r &gt; .98 between their estimates and the estimates calculated with the entire test. The first simulation also showed that, using the best performing ISA, 368 (53.5%) participants needed to answer at least one fewer item without loss of validity. The second study showed that the STEU stood to benefit the most, with the mean standard error (MSE) being minimized six items before the end of the test, though ISAs based on the Kullback–Leibler information performed worse. However, these ISAs also displayed slightly less bias, , than the Fisher information-based ones . For the STEM, no ISA minimized MSE levels before the end of the test, but up to six fewer items for the STEM and 15 fewer items for the STEU could be administered with a slightly higher tolerance of ΔSE &lt; . These results indicate that the use of CAT methodology to administer these tests is viable, and EI testing stands to gain from using CAT tests. Future studies should test ISA performance with additional testing constraints.

INVESTIGATION OF A POINT-OF-CARE VISCOELASTIC COAGULATION MONITOR AND ITS COMPARISON TO THROMBOELASTOGRAPHY IN CLINICALLY HEALTHY AFRICAN ELEPHANTS (LOXODONTA AFRICANA).

Elephant endotheliotropic herpesvirus (EEHV) can induce fatal hemorrhagic disease (HD) in African elephants (Loxodonta africana). Once clinical signs develop, progression is rapid, even with aggressive treatment. There is a critical need to develop point-of-care diagnostic tests to aid in identification of EEHV-HD prior to the onset of overt clinical signs. Study objectives were to investigate a novel, point-of-care viscoelastic coagulation monitor (VCM Vet), compare the results to thromboelastography (TEG), and report traditional hemostatic analytes in adult African elephants. Whole blood was collected from seven clinically healthy elephants (four females and three males, 18-47 yr) and analyzed in duplicate via VCM Vet and kaolin-activated TEG 1-3 and 30 min following collection, respectively. Separated plasma was frozen for ancillary coagulation testing. Both analyses generated quantifiable clotting reactions with variables (median [range]) describing clot formation rate (VCM Vet, clot time = 682 s [530-987 s], clot formation time = 244 s [186-744 s], Alpha = 40° [14-47°]; TEG, reaction time = 6.2 min [3.7-11.8 min], kinetic time = 1.3 min [0.9-2.6 min], Alpha = 70° [57-77°]), clot strength (VCM Vet, maximum clot formation = 34 units [20-45 units]; TEG, maximum amplitude = 75 mm [69-80 mm], shear elastic modulus strength = 14.7 Kdynes/s [11.3-19.5 Kdynes/s]), and clot lysis (VCM Vet, lysis index at 30 min = 100% [100-99%], lysis index at 45 min = 98% [95-100%]; TEG, lysis index at 30 min = 0% [0-0.4%], lysis index at 60 min = 1.4% [0-2.6%]) recorded. Additional testing (median [range]) included D-dimer concentration (33 ng/ml [28-94 ng/ml]), prothrombin time (12.4 s [12.2-13.2 s]), activated partial thromboplastin time (17.2 s [14.2-18.8 s]), and fibrinogen concentration (297 [282-383] mg/dL). Tracings generated by VCM Vet and TEG were clinically similar, and there was visual agreement and minimal difference between quantitative variables for duplicate tests. VCM Vet is a promising, user-friendly tool for use in identification and management of coagulopathies in African elephants.

At-home testing for respiratory viruses: a minireview of the current landscape.

The landscape of at-home testing using over-the-counter (OTC) tests has been evolving over the last decade. The United States Food and Drug Administration Emergency Use Authorization rule has been in effect since the early 2000s, and it was widely employed during the severe acute respiratory syndrome coronavirus 2 pandemic to authorize antigen and nucleic acid detection tests for use in central laboratories as well as OTC. During the pandemic, the first at-home tests for respiratory viruses became available for consumer use, which opened the door for additional respiratory virus OTC tests. Concerns may exist regarding the public's ability to properly collect samples, perform testing, interpret results, and report results to public health authorities. However, favorable comparison studies between OTC testing and centralized laboratory test results suggest that OTC testing may have a place in healthcare, and it is likely here to stay. This mini-review of OTC tests for viral respiratory diseases will briefly cover the regulatory and reimbursement environment, current OTC test availability, as well as the advantages and limitations of OTC tests.

Time-varying spillovers in high-order moments among cryptocurrencies

This study uses high-frequency (1-min) price data to examine the connectedness among the leading cryptocurrencies (i.e. Bitcoin, Ethereum, Binance, Cardano, Litecoin, and Ripple) at volatility and high-order (third and fourth orders in this paper) moments based on skewness and kurtosis. The sample period is from February 10, 2020, to August 20, 2022, which captures a pandemic, wartime, cryptocurrency market crashes, and the full collapse of a stablecoin. Using a time-varying parameter vector autoregressive (TVP-VAR) connectedness approach, we find that the total dynamic connectedness throughout all realized estimators grows with the time frequency of the data. Moreover, all estimators are time dependent and affected by significant events. As an exception, the Russia–Ukraine War did not increase the total connectedness among cryptocurrencies. Analysis of third- and fourth-order moments reveals additional dynamics not captured by the second moments, highlighting the importance of analyzing higher moments when studying systematic crash and fat-tail risks in the cryptocurrency market. Additional tests show that rolling-window-based VAR models do not reveal these patterns. Regarding the directional risk transmissions, Binance was a consistent net transmitter in all three connectedness systems and it dominated the volatility connectedness network. In contrast, skewness and kurtosis connectedness networks were dominated by Litecoin and Bitcoin and Ripple were net shock receivers in all three networks. These findings are expected to serve as a guide for portfolio optimization, risk management, and policy-making practices.