In this paper, we discuss how to synthesize stabilizing Model Predictive Control (MPC) algorithms based on convexly parameterized Integral Quadratic Constraints (IQCs), with the aid of general multipliers. Specifically, we consider Lur’e systems subject to sector-bounded and slope-restricted nonlinearities. As the main novelty, we introduce point-wise IQCs with storage in order to accordingly generate the MPC terminal ingredients, thus enabling closed-loop stability, strict dissipativity with regard to the nonlinear feedback, and recursive feasibility of the optimization. Specifically, we consider formulations involving both static and dynamic multipliers, and provide corresponding algorithms for the synthesis procedures. The major benefit of the proposed approach resides in the flexibility of the IQC framework, which is capable to deal with many classes of uncertainties and nonlinearities. Moreover, for the considered class of nonlinearities, our method yields larger regions of attraction of the synthesized predictive controllers (with reduced conservatism) if compared to the standard approach to deal with sector constraints from the literature.

The researcher will introduce the way of effective liquid chromatography tandem mass spectrometric method (HPLC-MS) which is quick, sensitive, and alternative to determine the (E)-3-(3,4-dihydroxyphenyl) -2-(3-(3,4-dihydroxyphenyl)acrylamido)propanoic acid (A1) and rosmarinic acid (RA) of the plasma in rats. The analyses were divided into a C18 column (1.9 μm, 2.1 mm × 100 mm) with a security guard C18 column (5 μm, 2.1 mm × 10 mm) and a triple-quadrupole mass spectrometry with an electrospray ionization (ESI) ion-source generates ions. With Pseudoephedrine hydrochloride being a standard, the sample pretreatment is relevant to the one-step protein precipitation with isopropanol: ethyl acetate (v/v, 20:80). This method presented a linear relationship within ranges of the concentration of 5–750 ng/ml for RA and A1. Relative standard deviations (RSD) in daily courses stood less than 15% and the relative errors (RE) registered within 15%. The means adopted in this research makes the RA’s and A1’s unambiguous quantification and identification and in vivo possible. And this study can be the first one to focus on determining the A1 and RA of rat plasma with administration orally. The results served as a significant basis to evaluate the medicine’s applications in the clinic.

Purpose: Reducing initial exposure of “opioid naïve” patients to opioids is a public health priority. Identifying opioid naïve patients is difficult, as numerous definitions are used. The objective is to summarize current definitions and evaluate their impact on opioid naïve measures in Alberta. Methods: Using dispense data (2017-2021) and definitions guided by a scoping review, we determined the number of “opioid naïve” patients using descriptive analyses. Three definitions were identified: 1) no opioid use within the previous 30 days/6 months/1 year, based on dispensation date; 2) definition 1, based on dispensation date plus days of supply; 3) exclusion of codeine from definitions 1 and 2. Results: Of over a dozen definitions of opioid naïve identified in the scoping review, most used an ‘opioid free’ period (commonly 30 days/6 months/1 year). Other definitions included “availability of drug” based on days of supply and/or excluded certain opioid products. Approximately 36.4% of Albertans (n=1,551,075) had an opioid dispensation in 2017-2021. The average age was 46.6±18.8 and 52.8% were female. Results were most affected by the “opioid free” period, with 97.4%, 83.2% and 65.6% being classified as opioid naïve using time windows from definition 1. Definitions 2 and 3 did not materially change the results. Conclusions: The most convenient definition for “opioid naïve” was definition 1 using a 1-year window, which aligns with the Canadian Institutes for Health Information definition. Irrespective of definition used, a large proportion of opioid users would be considered opioid naïve despite initiatives to curb opioid prescription in Alberta.

Background Based on previous reports of disparities in financial burden following cancer, this study aims to characterize mechanisms of disparities experienced by caregivers of children with cancer, including the impact of work flexibility and social support. Methods Cross-sectional survey (in English or Spanish) of caregivers of children with cancer that assessed household material hardship (HMH), financial toxicity and income change. Results Of 156 caregivers surveyed, 32% were Hispanic and 32% were low income. Hispanic caregivers were more likely to report HMH and financial toxicity compared to non-Hispanic White and Asian (HMH 57% v. 21% v. 19%, p<0.001; financial toxicity 73% v. 52% v. 53%, p=0.07). Low and middle income caregivers were more likely to experience HMH and financial toxicity compared to high income (HMH: 68% low v. 38% middle v 8.7% high, p<0.001; financial toxicity: 81% v. 68% v. 44%, p<0.001). All income categories demonstrated significant increases in HMH one year after diagnosis. Seventeen percent reported >40% income loss, more of whom were low income than high income (27% v. 12%, p=0.20). Work flexibility and social support were associated with income and financial toxicity. Conclusion HMH, financial toxicity, and income loss are prevalent after a child’s cancer diagnosis, suggesting that screening should be incorporated into routine care. This financial burden disproportionately affects low income and Hispanic caregivers. Further research is underway to understand how safety net services are utilized by families, how best to support families with HMH, and how the financial burden of cancer has been impacted by COVID-19.

Consumption of foods contaminated with aflatoxin B1 (AFB1) is a recognized risk factor for developing hepatocellular carcinomas (HCCs). The mutational signature of AFB1 is characterized by high frequency G > T transversions in a limited subset of trinucleotide sequences. The 8,9-dihydro-8-(2,6-diamino-4-oxo-3,4-dihydropyrimid-5-yl-formamido)-9-hydroxyaflatoxin B1 (AFB1-FapyGua) has been implicated as the primary DNA lesion responsible for AFB1-induced mutations. This study evaluated the mutagenic potential of AFB1-FapyGua in four contexts, including hot- and cold-spot sequences as apparent in the mutational signature. Vectors containing AFB1-FapyGua were replicated in primate cells and the products of replication were isolated and sequenced. Regardless of the sequence context, AFB1-FapyGua caused base substitutions at frequencies of ~ 80-90%, with G > T transversions being most common. Spectra of mutations were only slightly modulated by the sequence context. These data suggest that mechanism(s) defining sequence context-dependent distribution of AFB1-induced mutations likely operates prior to replication.

There are few reports of the adoption of continuous processes in bioproduction, particularly the implementation of end-to-end continuous processes, due to difficulties such as feed adjustment, production batch demarcation, and incorporating virus filtration. Here, we propose an end-to-end continuous process for a monoclonal antibody (mAb) with three integrated process segments: upstream production processes with pool-less direct connection, pooled low pH virus inactivation with automated pH control and a total flow-through integrated polishing process in which two columns were directly connected with a virus filter. The pooled virus inactivation step demarcates the batch, and high impurities reduction and mAb recovery were achieved for batches conducted in succession. Viral clearance tests also confirmed robust virus reduction for the flow-through two column chromatography and the virus filtration steps. Additionally, viral clearance tests with two different hollow fiber virus filters operated at flux ranging from 1.5 to 40 LMH confirmed robust virus reduction over these ranges. Complete clearance with LRV ≥ 4 was achieved even with a process pause at the lowest flux. The end-to-end continuous process proposed in this study is highly applicable to production processes, and the investigated virus filters have excellent applicability to continuous processes conducted at constant flux.

Online Social Networks (OSNs) have grown exponentially in the last few years due to their applications in real life like marketing, recommendation systems, and social awareness campaigns. One of the most important research areas in this field is Influence Maximization (IM). IM pertains to finding methods to maximize the spread of information (or influence) across a social network. Previous works in IM have focused on using a pre-defined edge propagation probability or using the Hurst exponent (H) to identify which nodes to be activated. This is calculated on the basis of self-similarity in the time series depicting a user’s (node) past temporal interaction behaviour. In this work, we propose a Time Series Characteristic based Hurst-based Diffusion Model (TSC-HDM). The model calculates Hurst Exponent (H) based on the stationary or non-stationary characteristic of the time series. Furthermore, our model selects a handful of seed nodes and activates every seed node’s inactive successor only if H>0.5 . The process is continued until the activation of successor nodes is not possible. The proposed model was tested on 4 datasets - UC Irvine messages, Email EU-Core, Math Overflow 3, and Linux Kernel mailing list. We have also compared the results against 4 other Influence Maximisation models - Independent Cascade (IC), Weighted Cascade (WC), Trivalency (TV), and Hurst-based Influence Maximisation (HBIM). Our model achieves as much as 590% higher expected influence spread as compared to the other models. Moreover, our model attained 344% better average influence spread than other state-of-the-art models.

The prediction of news popularity is having substantial importance for the digital advertisement community in terms of selecting and engaging users. Traditional approaches are based on empirical data collected through surveys and applied statistical measures to prove a hypothesis. However, predicting news popularity based on statistical measures applied to past data is highly questionable. Therefore, in this paper, we predict news popularity using machine learning classification models and deep residual neural network models. Articles are usually made up of textual content and in many cases, images are also used. Although it is evident that the appropriate amount of textual data is required to extract features and create models, image data is also helpful in gaining useful information. In this paper, we present a novel multimodal online news popularity prediction model based on ensemble learning. This research work acts as a guide for extensive feature engineering, feature extraction, feature selection, and effective modeling to create a robust news popularity Prediction Model. Three kinds of features – meta features, text features, and image features are used to design an influential and robust model. The performance measure Root Mean Squared logarithmic error (RMSLE) is used to validate the outcome of the proposed model. Further, the most important features are sought out for the proposed model to verify the dependence of the model on text and image features.

A 19-year-old Cob mare with atrial fibrillation (AF) presented for transvenous electric cardioversion (TVEC). Under general anaesthesia, three successive incremental electric shocks were given (total 750 Joules) and sinus rhythm was temporarily restored. After 13 seconds, AF recurred so a fourth shock (300 Joules) was given and intravenous (IV) amiodarone started. Shortly after, capnography revealed an acute drop in the end-tidal carbon dioxide, which was followed by agonal gasping. Echocardiography showed severe cardiac dysfunction. Successful cardiac resuscitation consisted, amongst others, of cessation of amiodarone, and administration of dobutamine and adrenaline. This case report highlights the importance of capnography as a non-invasive means of cardiac output monitoring in equine anaesthesia which definitely contributed to a positive outcome. It also emphasises the critical importance of early recognition and communication of complications within anaesthetic and cardiology teams.

Protein glycosylation is the most complex and diverse form of post-translational modification in human body. Meanwhile, glycosylation of peptides and proteins emerges as a promising strategy to improve the pharmacokinetic profile of peptide- and protein-based therapeutics. Owing to the importance of protein glycosylation, rigorous evaluation of the relationship between the precise structure and biological function of glycoproteins has to be per-formed. Recently, chemical synthesis, chemoenzymatic synthesis and semisynthesis strategy have attracted extensive attentions towards the prepara-tion of structurally defined glycopeptides and glycoproteins; the obtained synthetic glycoforms thus enable the thorough investigation of specific effects of protein glycosylation. This review highlights the recent progress in the development of novel strategies, preparation of homogeneous glycoproteins and exploration of structure-activity relationships. On this basis, the challenges and prospects are discussed.

The ancient Greeks took the entertainment of their crowds very seriously and used drama as a way of investigating the world they lived in. The theatrical re-enactment of suffering and grief in front of a large audience was to foster compassion, as well as a cathartic release of emotion that was restorative through a deeply felt interconnection between actors and audience. When our patients encounter tragedy, we are also drawn into their ordeal and experience it first hand. Such it was with Rose.

The distribution of gas-liquid two-phase flow is one of significant effects on heterogeneous catalytic reactions. Ceramic membrane gas distributors (CMGD) were applied in improving gas-liquid distribution, and flow behavior of gas as dispersed phase in liquid phase was visualized via high-speed photograph. The average diameters of multi-scale bubbles were measured and modeled ranging from 10-5 to 10-2 m. The coalescence and trajectory of bubbles during rising process were observed, and two typical trajectories straight and spiral types were tracked. In order to inhibit coalescence of bubbles during rising process, internals manufactured by 3D printing were installed in the channel of ceramic membrane. The average bubble size of CMGD decreases 12 % from 392 to 345 μm compared to that of the original CMGD. The CMGD with internals enhances the heterogeneous catalytic reaction performance via providing large quantity of stabile multi-scale bubbles which could match the porous structure of catalyst.

One hundred fecal samples from hooded vultures in the Gambia (Banjul area) were investigated for the presence of bacteria with extended-spectrum cephalosporin- (ESBL/AmpC), carbapenemases, and colistin resistance. No Enterobacteriales carrying carbapenemases or resistance against colistin were detected. Fifty-four ESBL-producing Escherichia coli and five ESBL-producing Klebsiella pneumoniae isolates were identified in 52 of the samples, of which 52 E. coli and 4 K. pneumoniae yielded passed sequencing results. Fifty of the E. coli had ESBL phenotype and genotype harboring blaCTX-M genes, of which 88.5% (n=46) were the blaCTX-M-15 gene, commonly found on the African continent. Furthermore, the genetic context around blaCTX-M-15 was similar between isolates, being co-localized with ISKpn19. In contrast, cgMLST analysis of the E. coli harboring ESBL genes revealed a genetic distribution over a large fraction of the currently known existing E. coli populations in the Gambia. Hooded vultures in the Gambia thus have a high ESBL E. coli-prevalence (>50%) with low diversity regarding key resistance genes. Furthermore, given the urban presence and frequent interactions between hooded vultures and humans, data from this study implies hooded vultures as potential vectors contributing to the further dissemination of antibiotic-resistance genes.

Background: As the volume of cardiac imaging continues to increase, so is the number of tests performed for rarely appropriate indications. Appropriate use criteria (AUC) documents were published by professional societies with quality improvement (QI) interventions developed in various institutions. However, the effectiveness of these interventions has not been assessed in a systematic fashion. Methods: We performed a database search for studies reporting the association between cardiac imaging, AUC and QI. We selected studies assessing the effect of QI interventions on performance of rarely appropriate echocardiograms. The primary endpoint was reduction of rarely appropriate testing. Results: Nine studies with 22,070 patients met inclusion criteria. QI interventions resulted in statistically significant reduction in rarely appropriate tests (OR 0.52, 95% CI 0.41-0.66; p<0.01). The effects of QI interventions were analyzed over both the short (< 3 months) and long-term (> 3 months) post intervention (OR 0.62, 95% CI: 0.49-0.79; p<0.01 in the short term, and OR 0.47, 95% CI: 0.35-0.62; p<0.01 in the long term). Subgroup analysis of the type of intervention, classified as education tools or decision support tools showed both significantly reduced rarely appropriate testing (OR 0.54, 95% CI: 0.41-0.73; p<0.01; OR 0.47, 95% CI: 0.36-0.61; p<0.01). Adding a feedback tool did not change the effect compared to not using a feedback tool (OR 0.49 vs. 0.57, 95% CI: 0.36-0.68 vs. 0.39-0.84; p>0.05). Conclusion: QI interventions are associated with a significant reduction in performance of rarely appropriate echocardiography testing, the effects of which persist over time.

Novel Gonadotrophin Releasing Hormone (GnRH) antagonist treatments have recently been developed in combination with hormonal add-back therapy, as an oral treatment option for women suffering from uterine fibroids. Registration trials assessing the GnRH antagonist combination preparations with relugolix, elagolix, and linzagolix have assessed treatment efficacy for fibroid related heavy menstrual blood loss in comparison to placebo. Marketing authorization has already been granted by several agencies including those in Europe, the United Kingdom, and the United States. Prior to marketing authorization, the European Medicines Agency recommends that Phase III registration trails should assess treatment efficacy in a representative study population, assess relevant outcomes with a comparison to gold-standard alternative treatment options and that long-term safety data will adequately be collected. In this review, we demonstrate limitations in the trial data generated to date, namely a lack of generalizability due to the restricted population studied, the absence of any comparison to alternative treatment methods, and findings limited to specific subgroups of patients because of the type of outcomes assessed. Symptoms related to uterine fibroids adversely affect many women’s quality of life and effective medical treatments are lacking. However, despite the urgent need for effective treatments, it is vitally important that novel drugs, like combination oral GnRH antagonists, undergo sufficiently rigorous evaluation of safety, effectiveness, and cost-effectiveness in a representative population compared with alternative treatment methods before introduction into mainstream clinical practice.

Mechanical forces play a crucial role in biological processes at the molecular and cellular levels. Recent advancements in dynamic force spectroscopies (DFS) have enabled the application and measurement of forces and displacements with high resolutions, providing insights into the mechanical pathways involved in various diseases, including cancer, cardiovascular disease, and COVID-19. Among the various DFS techniques, biomembrane force probe (BFP) advancements have improved our ability to measure bond kinetics and cellular mechanosensing with pico-newton and nano-meter resolutions. In this review, we provide a comprehensive overview of the classical BFP-DFS setup and highlight key advancements, including the development of dual biomembrane force probe (dBFP) and fluorescence biomembrane force probe (fBFP). BFP-DFS not only enables the investigation of dynamic bond behaviors on living cells, but also contributed significantly to our understanding of the specific ligand–receptor axes mediated cell mechanosensing. Besides, we explore the contribution of discoveries made possible by BFP-DFS in cancer biology, thrombosis, and inflammation, as well as predict future BFP upgrades to improve output and feasibility. Although BFP-DFS is still a niche research modality, its contribution to the growing field of cell mechanobiology is unparalleled, and its potential to elucidate novel therapeutic discoveries is significant.

Postnatal cytomegalovirus (HCMV) infection is well characterized in preterm infants, where it can lead to severe symptomatic infection. We analyzed the rate and route of transmission of postnatal HCMV infections in full-term babies during the first year of life. A cohort of 120 HCMV seropositive mothers and their 122 newborns were tested after delivery for HCMV DNA shedding in different bodily fluids. Postnatal HCMV infection was defined as the detection of >2.5×10 2 HCMV-DNA copies/mL in infants’ saliva swabs. Maternal neutralizing antibody serum titer, HCMV specific T-cell response, and HCMV glycoprotein B (gB) IgG on breastmilk were analyzed. HCMV shedding was detected in 67 of 120 mothers (55.8%), and 20 of 122 infants (16.4%) developed HCMV infection within the first three months of life. Six additional infants were infected during the first year, for a postnatal infection rate of 21.3%. Viral shedding was more frequent in breastmilk than saliva, urine and vaginal secretions, and the mothers of infected infants showed higher levels of HCMV-DNA in milk. No association was found between the antibody levels in serum or milk and maternal viral shedding, whereas a slightly lower frequency of HCMV-specific CD4 + T-cells with long-term memory phenotype was observed in women with HCM-DNA-positive milk. About one out of five infants develop HCMV infection within the first year of life. Breastmilk appears the major route of transmission of the infection, maternal saliva have a minor role whereas the role of vaginal secretions is negligible.

SARS-CoV-2 causes COVID-19 pandemic and continues to pose a threat to global public health through genetic mutation. In this study, we have found that an ACE2-specific monoclonal antibody at low concentration was able to greatly enhance SARS-CoV-2 infection and growth in cell culture. Strikingly, it promotes SARS-CoV-2 plaque formation, resulting in accurate titration of different SARS-CoV-2 variants, particularly the newly emerged Omicron variants, which otherwise cannot be determined by standard plaque assays. Quantification of infectious titers of the newly emerged variants will facilitate the development and evaluation of vaccines and antiviral drugs against SARS-CoV-2.