Respiratory disease in weaned pigs is a common problem in the field, with a complex aetiology of both viruses and bacteria. In the present study, we investigated the presence of eleven viruses in nasal swabs collected from nurseries (fifty-five clinical outbreaks) under the suspicion of swine influenza A virus (swIAV) by cough and fever. The other ten viruses included influenza B (IBV) and influenza D viruses (IDV), Porcine reproductive and respiratory syndrome virus (PRRSV), Porcine respiratory coronavirus (PRCV), Porcine cytomegalovirus (PCMV), porcine circoviruses 2 (PCV2), 3 (PCV3) and 4 (PCV), Porcine parainfluenza 1 virus (PPIV1) and Swine orthopneumovirus (SOV). Twenty-nine swIAV-positive cases and twenty-six cases of swIAV-negative respiratory disease were primarily established. IBV, IBD, PCV4 and PPIV1 were not found in any case, while PRCV, SOV, and PCMV were more likely to be found in swIAV-positive nurseries with respiratory disease ( p<0.05) although, globally, PCV3, PRRSV, and PCMV were the most frequently detected agents on herd level. At an individual level, the prevalence of different viruses was: swIAV 48.6%; PRCV 48.0%; PRRSV 31.6%; SOV 33.8%; PCMV 48.3%, PCV2 36.0%; and PCV3 33.0%. Beyond that, it was common to find animals with low Ct values (< 30) for all agents except for PCV2 and PCV3. When analysed the association between different pathogens, PRCV was the one with the most associations. It positively interacted ( p < 0.05) with swIAV and SOV but was negatively associated ( p < 0.05) with PRRSV and PCVM. Besides these, swIAV and PRRSV were negatively related (p < 0.05). Further analysis of suckling pigs showed that circulation of PRCV, PCMV, SOV, and PCV3 started in the maternities, suggesting a role of the sows in the transmission. Overall, our data may contribute to a better understanding of the complex aetiology and the epidemiology of respiratory disease in weaners. This is the first report of SOV in Spain.

Aim To evaluate ventricular synchronization and function in patients with right bundle-branch block after left bundle-branch-area pacing (LBBAP) by echocardiography. Methods Forty patients who successfully received LBBAP were selected and divided into the right bundle-branch block group (RBBB group) and the non-RBBB group by pre-operation ECG. Echocardiography and follow-up were performed 1 month after operation. Interventricular synchronization was evaluated by tissue Doppler (TDI), tissue mitral annular displacement (TMAD), and interventricular mechanical delay (IVMD). The ventricular longitudinal strain and the standard deviation of peak time of longitudinal strain were analyzed by two-dimensional speckle tracking imaging (2D-STI) to evaluate intraventricular synchronization and ventricular function. Results (1) The deviation of systolic time to the peak of the tricuspid and mitral valves, namely ΔPTTV-MV measured by TMAD and ΔTsTV-MV measured by TDI, were statistically different between the two groups (P < 0.05). (2) Compared with the non-RBBB group, there were no statistically significant differences in longitudinal strain (LS), peak strain time, standard deviation of peak strain time (SDt), and global longitudinal strain (GLS) in the right and left ventricle in the RBBB group (P > 0.05). Conclusion Echocardiography technology including 2D-STI, TDI, and TMAD can effectively analyze interventricular synchronization, intraventricular synchronization, and ventricular function. Although the movement of the right ventricular myocardium in the RBBB group treatment was slightly later than that of the left ventricular myocardium after LBBAP, LBBAP is still an effective pacing therapy for RBBB patients with pacing indication.

Abstract. The purpose of this study is to introduce a tripled quasi-metric and prove some fixed point theorems involving -implicit contractions in tripled quasi-metric spaces. An example and an application on a solution of a integral equation are also presented.

In this paper, we investigate the initial value problem of a nonlocal sine-type µ-Camassa-Holm (µCH) equation, which is the µ-version of the sine-type CH equation. We first discuss its local well-posedness in the framework of Besov spaces. Then a sufficient condition on the initial data is provided to ensure the occurance of the wave-breaking phenomenon. We finally prove the H¨older continuity of the data-to-solution map, and find the explicit formula of the global weak periodic peakon solution.

The study addresses the reduction of ethylene levels in postharvest storage applications using a Pd-Zn-Sn/TiO2 catalyst, which is capable of reacting trace concentrations of ethylene at temperatures as low as 278 K and at relative humidity as high as 90%. The rate law is derived from data collected using a constant volume batch reactor and a model for a storage room with associated packed bed reactor is developed. The amount of catalyst required to maintain an ethylene concentration of 0.1 ppmv in a room containing 20 tons of fruit having an ethylene metabolism of 0.1 ul/kg hr was calculated as a function of air temperature and water content. While the catalyst is capable of continuously removing ethylene from saturated, refrigerated air, the amount of catalyst required can be reduced significantly by incorporating conventional air conditioning solutions upstream of the catalyst bed. Such combined systems and their functions are discussed

The effects of particle concentration and size on hydrodynamics and mass transport in a slurry bubble column were experimentally studied. With increasing particle concentration, the averaged gas holdup, gas holdup of small bubbles and gas-liquid volumetric mass transfer coefficient decreased, while the gas holdup of large bubbles increased slightly. With increasing particle size, the averaged gas holdup and kla remained unchanged when the particle size increased from 55 to 92 m, but decreased significantly when the particle size was further increased to 206 m. A liquid turbulence attenuation model which could quantitatively describe the effects of particle concentration and size was first proposed. Semi-empirical correlations were obtained based on extensive experimental data in a wide range of operating conditions and corrected liquid properties. The gas holdup and mass transfer coefficient calculated by the correlations agreed with the experimental data from both two-phase and three-phase bubble columns

Manuscript title:Sustainable medicines use in clinical practice – it is time to help the teacher

Introduction: There is increasing evidence of the epicardial connection between the right-sided pulmonary vein (PV) carina and right atrium interrupts right-sided PV isolation after circumferential PV ablation in patients with atrial fibrillation. In such cases, carina ablation is often required. This study aimed to assess the utility of the right atrial posterior wall (RAPW) pacing in the detection of the right-sided epicardial connection (EC), evaluate the requirement for additional carina ablation after circumferential pulmonary vein (PV) ablation depending on the presence of EC, and investigate the clinical characteristics including the amount of epicardial adipose tissue (EAT) in patients with ECs. Methods and Results: Forty-one patients scheduled for PV isolation were enrolled. Before ablation, activation mapping of the LA was prospectively performed during pacing from the RAPW. EC was observed in 12 patients (EC group, 29%), whereas no EC was observed in the remaining 29 patients (non-EC group, 71%). For PV isolation, carina ablation was required in addition to circumferential ablation in 7 patients (58%) in the EC group, compared to 2 patients (7%) in the non-EC group (p < 0.003). Periatrial and intercaval EAT volumes were significantly lower (12.8 ± 6.2 vs. 23.1 ± 13.9 ml/m 2, p < 0.02, and 1.1 ± 0.8 vs. 2.2 ± 1.6 ml/m 2, p< 0.02, respectively) and the patients were younger (66.5 ± 6.6 vs. 72.4 ± 8.3 years, p < 0.03) in the EC group than in the non-EC group. Conclusions: RAPW pacing revealed EC between the RA and right PV carina in nearly a quarter of the patients.

Studies have demonstrated that protease activated receptors (PARs) with four subtypes (PAR1-4) are mainly expressed in the renal epithelial, endothelial and podocyte cells. Evidently, the PAR-1 and PAR-2 have shown differential therapeutic outcomes in rodent models of type-1 and type-2 diabetic kidney diseases due to distinct etiological basis of each disease type. Both PAR-1 and PAR-2 blockers/knock-out have abolished the drug-induced nephrotoxicity in rodents by suppression of tubular inflammation and fibrosis. Notably, PAR-2 inhibition was found to improve autophagy in the urethral obstruction model. Only the PAR-1/4 subtypes have emerged as a therapeutic target for the treatment of experimentally induced nephrotic syndrome where their respective antibodies attenuated the podocyte apoptosis. So far the PAR-2/PAR-4 subtypes involvement has been tested in sepsis acute kidney injury and renal ischemia-reperfusion model. This review discusses the existing gaps, therapeutic advances and future perspectives related to the roles of different PARs in kidney diseases.

Background: Transcatheter mitral valve implantation (TMVI) is a promising and minimally invasive treatment for high-risk mitral regurgitation (MR). The purpose of this study was to investigate the feasibility of a novel self-expanding valved stent for transcatheter mitral valve implantation via apical access. Methods: A novel self-expanding mitral valved stent system was designed and fabricated for the in vivo evaluation. It is consists of an atrial flange and a saddle-shaped ventricular body connected by two opposing anchors and two opposing extensions. During the valve deployment, each anchor is controlled by a recurrent string. TMVI was performed in ten pigs using the valve prosthesis through the apical access to verify technical feasibility. Echocardiography and ventricular angiography were used to assess hemodynamic data and valve function. The surviving pigs were sacrificed four weeks later to confirm stent deployment. Results: Ten animals underwent transapical mitral valve implantation with the novel mitral valved stent. Optimal valve deployment and accurate anatomical adjustment were obtained in nine animals. Implantation failed in one case, and the animal died one day later due to stent mismatch. After stent implantation, the hemodynamic parameter of other animals was stable and valve function was normal. The mean pressure across the mitral valve and left ventricular outflow tract (LVOT) were 2.98±0.91mmHg and 3.42±0.66 mmHg, respectively. The macroscopic evaluation confirmed the stable and secure positioning of the stents in the mitral valve. No obvious valve displacement, embolism, and paravalvular leakage were observed four weeks after valve implantation. Conclusions: This study proved that the novel mitral valved valve stent is technically feasible in animals. This device features opposing anchors, opposing recurrent strings, and saddle-like ventricular portions, providing structural design details for reducing TMVI complications. However, the long-term feasibility and durability of this valved stent need to be improved and verified.

OBJECTIVE(S): to evaluate the severity of HDFN in subsequent pregnancies with RhD immunization and to identify predictive factors for severe disease. DESIGN: prospective cohort. SETTING: the Netherlands. POPULATION: nationwide selection of all pregnant women with RhD antibodies. METHODS: women with two subsequent RhD immunized pregnancies with RhD-positive children after antibodies were detected were included. MAIN OUTCOME MEASURE: the severity of HDFN in the first and subsequent pregnancy at risk. RESULTS: 62 RhD immunized women with a total of 150 RhD-positive children were included. The severity of HDFN increased significantly in the subsequent pregnancy (P<.001), although it remained equal or even decreased in 44% of women. When antibodies were already detected at first trimester screening in the first immunized pregnancy, severe HDFN in the next pregnancy was uncommon (22%), especially when no therapy or only non-intensive phototherapy was indicated during the first pregnancy (6%), or if the ADCC result remained <10%. Contrarily, women with antibodies detected during the first pregnancy of a RhD positive child (>= 27th week), most often before they had ever received RhIg prophylaxis, were most prone for severe disease in a subsequent pregnancy (48%). CONCLUSION(S): RhD-mediated HDFN in a subsequent pregnancy is generally more severe than in the first pregnancy at risk and can be estimated using moment of antibody detection and severity in the first immunized pregnancy. Women developing antibodies in their first pregnancy of a RhD-positive child are at highest risk of severe disease in the next pregnancy.

We explored the relative importance of climate oscillations and human-driven disturbances on the change of vegetation biomass in agroecosystems, and whether it is associated with land use. The study was carried out in the drylands of the Iberian Peninsula, NW Maghreb, Palestinian West Bank, Mozambique, China and NE Brazil, using satellite time-series and the corresponding climate fields, at ten-year observation periods with spatial and temporal resolutions of 1000 m (250 m in Palestine) and one year, respectively. For each region, we separated the relative weights of climate and time by fitting multiple-stepwise regressions to a vegetation index as the dependent variable, and annual aridity (Aridity) and year number (Time) as predictors. The relative strength of the resulting standard partial regression coefficients was then compared by the Wilcoxon Signed Ranks test, and their combined associations with land uses were determined using chi-square tests. Some points of convergence are: 1. The relative weights of Aridity and Time depend on particular regional conditions and can be determined. 2. Such weights are associated with land use intensification, such that if vegetation increases over Time, Aridity increases its relative importance with intensification; if vegetation is degrading, Aridity is always more important than Time. 3. Aridity is an indicator of vulnerability to climate warming. Resilience can be improved by reducing land use intensification. 4. Vulnerability may worsen under constant climate if agriculture is intensified. These patterns enhance an integrated understanding of Sustainable Development Goals Indicator 15.3.1, particularly its land cover and productivity trend components.

In the context of atrial fibrillation (AF), traditional clinical practices have thus far fallen short in several domains such as identifying patients at risk of incident AF or patients with concomitant undetected paroxysmal AF. Novel approaches leveraging artificial intelligence have the potential to provide new tools to deal with some of these old problems. In this review we focus on the roles of artificial intelligence-enabled ECG pertaining to AF, potential roles of deep learning (DL) models in the context of current knowledge gaps, as well as limitations of these models. One key area where DL models can translate to better patient outcomes is through automated ECG interpretation. Further, we overview some of the challenges facing AF screening and the harms and benefits of screening. In this context, a unique model was developed to detect underlying hidden AF from sinus rhythm and is discussed in detail with its potential uses. Knowledge gaps also remain regarding the best ways to monitor patients with ESUS and who would benefit most from oral anticoagulation. The AI-enabled AF model is one potential way to tackle this complex problem as it could be used to identify a subset of high-risk ESUS patients likely to benefit from empirical oral anticoagulation. Role of DL models assessing AF burden from long duration ECG data is also discussed as a way of guiding management. There is a trend towards the use of consumer-grade wristbands and watches to detect AF from photoplethysmography data. However, ECG currently remains the gold standard to detect arrythmias including AF. Lastly, role of adequate external validation of the models and clinical trials to study true performance is discussed.

Background: Implantable cardioverter defibrillators (ICD) are indicated for primary and secondary prevention of sudden cardiac arrest. Despite enhancements in design and technologies, the ICD lead is the most vulnerable component of the ICD system and failure of ICD leads remains a significant clinical problem. A novel, small diameter, lumenless, catheter delivered, defibrillator lead was developed with the aim to improve long term reliability. Methods and Results: The Lead Evaluation for Defibrillation and Reliability (LEADR) study is a multi-center, single-arm, Bayesian, adaptive design, pre-market interventional pivotal clinical study. Up to 60 study sites from around the world will participate in the study. Patients indicated for a de novo ICD will undergo defibrillation testing at implantation and clinical assessments at baseline, implant, pre-hospital discharge, 3 months, 6 months, and every 6 months thereafter until official study closure. Patients will participate for a minimum of 18 months to approximately 3 years. Fracture-free survival will be evaluated using a Bayesian statistical method that incorporates both virtual patient data (combination of bench testing to failure with in-vivo use condition data) with clinical patients. The clinical subject sample size will be determined using decision rules for number of subject enrollments and follow-up time based upon the observed number of fractures at certain time points in the study. The adaptive study design will therefore result in a minimum of 500 and a maximum of 900 patients enrolled. Conclusion: The LEADR Clinical Study was designed to efficiently provide evidence for short- and long-term safety and efficacy of a novel lead design using Bayesian methods including a novel virtual patient approach.

Emerging plant pathogens have been increasing exponentially over the last century. To address this issue, it is critical to determine whether these pathogens are native to ecosystems or have been recently introduced. Understanding the ecological and evolutionary processes fostering emergence can help to manage their spread and predict epidemics/epiphytotics. Using restriction site-associated DNA sequencing data, we studied genetic relationships, pathways of spread, and evolutionary history of Phellinus noxius, an emerging root-rotting fungus of unknown origin, in eastern Asia, Australia, and the Pacific Islands. We analyzed patterns of genetic variation using Bayesian inference, maximum likelihood phylogeny, populations splits and mixtures measuring correlations in allele frequencies and genetic drift, and finally applied coalescent based theory using Approximate Bayesian computation (ABC) with supervised machine learning. Population structure analyses revealed five genetic groups with signatures of complex recent and ancient migration histories. The most probable scenario of ancient pathogen spread is movement from ghost population to Malaysia and the Pacific Islands, with subsequent spread to Taiwan and Australia. Furthermore, ABC analyses indicate that P. noxius spread occurred thousands of generations ago, contradicting previous assumptions that this pathogen was recently introduced to multiple geographic regions. Our results suggest that recent emergence of P. noxius in eastern Asia, Australia, and the Pacific Islands is likely driven by anthropogenic and natural disturbances, such as deforestation, land-use change, severe weather events, and/or introduction of exotic plants. This study provides a novel example of applying genome-wide allele frequency data to unravel dynamics of pathogen emergence under changing ecosystem conditions.

Background and aim of the study. Wrapping of the ascending aorta (AA), isolated or associated with aortoplasty, has never been completely accepted. Some complications, as folding of the aortic wall, compression of the vasa vasorum and changes in the flow pattern, with consequent dilatation of the proximal arch, have been described. We used fresh autologous pericardium (FAP), so far never reported, to wrap the AA, with the aim to stabilize its size when moderately dilated, maintaining the preoperative dimension or limiting the reduction to a few mm. Material and Methods. From 2015 to 2019, 10 patients, who were operated on for valve or coronary surgery or both, underwent wrapping of the AA with FAP. Mean age was 69±7 years and ESII 3.5±1.7. Four patients had moderately impaired ejection fraction (35-49%). Results. There was no early or late mortality. One patient was reoperated on after 48 months for severe mitral regurgitation. At a follow up of 53±14 months, a transthoracic echocardiogram showed that the AA size reduced slightly but significantly, from 45.2±2.0 to 42.5±4.1 mm, p=0.03. The diameter of the proximal arch remained unchanged, from 37.1±1.6 to 36.3±2.9 mm, p=0.20. Conclusions. In presence of moderately dilated AA wrapping can be a reasonable option. The use of FAP stabilizes the size of the aorta after a follow up of 53 months. Maintaining a size similar to the preoperative one avoids the complications related to the procedure.

Pericardiectomy for Constrictive Pericarditis after Mediastinal Irradiation – Need for Functional AssessmentSiddharth Pahwa, MD1

Anomalous coronary arteries arise in a small subset of the population, with each configuration conveying a varying degree of long-term risk. In this report, we describe the discovery of an anomalous single coronary artery with the left main coronary artery arising from the right coronary ostium in a 40-year old male evaluated for cardiac donation. After evaluation, this heart was successfully procured and utilized for orthotopic heart transplantation.

Gitelman syndrome (GS) is a kind of salt-losing tubular disease, most of which is caused by SLC12A3 gene variants, and missense variants account for the majority. Recently, the phenomenon of exon skipping, in which exonic variants disrupt normal pre-mRNA splicing, has been related to a variety of diseases. The purpose of this study was to identify the effect of previously presumed missense SLC12A3 variants on pre-mRNA splicing using bioinformatics tools and minigenes. The results revealed that, among ten candidate variants, six variants (c.602G>A, c.602G>T, c.1667C>T, c.1925G>A, c.2548G>C and c.2549G>C) led to complete or incomplete exon skipping by affecting exonic splicing regulatory elements and/or disturbing canonical splice sites. It is worth mentioning that this is the largest study on pre-mRNA splicing of SLC12A3 exonic variants. In addition, our study emphasizes the importance of detecting splicing function at the mRNA level in GS and indicates that minigene analysis is a valuable tool for splicing functional assays of variants in vitro.

One of the negative effects of hydropower on river environment includes rapid changes in flow and habitat conditions. Any sudden flow change could force fish to move towards a refuge area in a short period of time, causing serious disturbances in the life cycle of the fish. A probability-based multiscale model was developed to quantify the impact of hydropeaking on habitat suitability for two fish species. The model used habitat preference curves, river flow and depth to develop the suitability maps. The suitability index maps reveal that habitat suitability deteriorates as flow increases in this part of the river. The probability model showed that, on average, suitability indices are higher for adult grayling than juvenile trout in hydropeaking events in the studied area. In addition, the life stages of fish determine their response to the sudden flow change. The method developed shows the potential to be used in river management and the evaluation of hydropeaking impacts in river systems affected by hydropower.

Understanding the factors that increase the transmissibility of the recently emerging variants of SARS-CoV-2 can aid in mitigating the COVID-19 pandemic. The enhanced transmissibility could be attributed to enhanced within-host processes, such as contagiousness (viral shedding by an infected individual) and infectivity (the probability of a susceptible individual to get infected), or outside-host processes, such as viral stability on surfaces and in the air. We utilized a mathematical model in order to theoretically analyze the specific mechanisms of virus transfer between an infected and susceptible individual. This allowed us to examine how the within-host or outside-host processes affect the overall viral transmission. Our analysis is based the available data on the Alpha, Epsilon and Delta variants as well as the currently emerging Omicron variant. We found that the higher transmissibility of the SARS-CoV-2 variants can be attributed only to within-host processes. Specifically, enhanced contagiousness drives the Delta variant transmissibility, while the Alpha, Epsilon and Omicron are characterized by an enhanced infectivity. Since outside-host processes have little contribution to the observed increase in the transmissibility, leading stricter hygienic and behavioral measures than those that were already applied are not expected to achieve a pronounced mitigating effect.

Intensive clear cutting of natural forests and conversion to monoculture plantations are ongoing worldwide, leading to degradation of soil quality and microbial functions. Here, we compared soil quality index (SQI) and fungal community in a natural forest (Forest) and four 5-year-old monoculture plantations, including Camellia oleifera (Oil), Amygdalus persica (Peach), Myrica rubra (Berry) and Cunninghamia lanceolata (Fir), in a subtropical region of China. After conversion, soil pH rose up to 0.31, but organic carbon, total nitrogen, sucrase, acid protease, glutaminase and phosphatase activities decreased by 83%, 59%, 43%, 31%, 64%, 66% and 77%, respectively, in the plantations. Correspondingly, the SQI dropped by 65%. High-throughput sequencing of the ITS1 region demonstrated an increase in α-diversity and a striking difference in β-diversity following conversion. Changes in the dominant fungal taxa following forest conversion to plantations was interpreted by Grime’s C-S-R life history framework. Conversion increased the fungal groups with stress-tolerant (S) and ruderal (R) strategies - mainly copiotrophic saprophytes, such as Ascomycota and Zygomycota, but decreased the fungal groups with competitor (C) strategies - mainly oligotrophic saprophytes and mycorrhizal fungi, such as Basidiomycota. Genera affiliated to those phyla including Pseudophialophora, Rhytisma increased, but Russula decreased. Redundancy analysis and structural equation modeling indicated that the diversity and composition of fungal communities changed with soil quality degradation, which were mainly driven by increased soil pH, decreased available carbon and nutrients (N, P), and related enzymes activities.

Congenital Granular Cell Tumour (CGCT) is a rare benign lesion and presents in newborn as fibrous mass arising from the alveolus.The prenatal screening of lesion can help in parent counselling, determining the complications, as larger size lesion may interfere with normal delivery and require caesarean section.

Background: Concerns about virus spread during surgery contributed to changes in the clinical management of ectopic pregnancies (EP) during the COVID19 pandemic. Objective: To compare published data on EP management prior versus during the COVID-19 pandemic and evaluate any difference in the management, rupture rate and complications where Early Pregnancy Unit (EPU) structures exist. Search strategy: We performed a systematic review of the literature using a keyword strategy based on our PICO criteria. Selection criteria: We included studies which recruited women diagnosed with ectopic pregnancy and compared the management during and prior the COVID-19 pandemic peak. Data collection and Analysis: Three independent reviewers screened the literature and extracted the data. Meta-analysis of the data was performed on Revman. Main Results: Our search yielded 34 studies; 12 were included in our meta-analysis (3122 women). We found no difference in the type of management of EP between the pre-Covid and Covid cohorts [2714 women, OR 0.99(0.63-1.55), p=0.96, I2=77%]. We observed a non-statistically significant reduction of surgical management within the EPU branch ([OR 0.47(0.19-1.13), p=0.09, I2=81%]). There was no difference in the ectopic rupture rate in units with EPU [OR= 0.66 (0.33-1.31), p=0.24, I2=37%]. In contrast, in non-EPU (NPEU) the risk of ruptured EP [OR=2.86(1.84-4.46), p<0.01 I2=13%] and complications [OR=1.69(1.23-2.31), p=0.001, I2=45%] were increased. Conclusions: The worldwide trend was not reflected in the UK suggesting that EPU may have contributed to prompt diagnosis and safe management of EP. Funding: No funding was received. Keywords: ectopic pregnancy, COVID 19, meta-analysis, early pregnancy unit