Abstract Objective:Evaluate deformable slice-to-volume registration (DSVR) to calculate 3D-segmented total lung volume (TLV) in fetuses with congenital diaphragmatic hernia, congenital lung lesions and healthy controls, with comparison to 2D-manual segmentation. Design:Pilot study Setting:Regional fetal medicine referral centre Sample:Fetal MRIs performed for clinical indications (abnormal cases) or as research participants (healthy controls) Methods:Sixteen MRI datasets of fetuses (22-32 weeks GA). Diagnosis: CDH(n=5), CPAM(n=2), CDH with BPS(n=1) and healthy control(n=8). DSVR was used for reconstruction of 3D isotropic (0.85 mm) volumes of fetal body followed by semi-automated lung segmentation. The resulting 3D TLV were compared to the traditional 2D-based volumetry, and a normogram of DSVR-derived fetal lung volumes from 100 cases was produced. Main Outcome Measures:Concordance with 2D-volumetry assessed with Bland-Altman analysis, results of segmentations presented visually. Observed/Expected values were calculated for abnormal cases based upon the normogram. Results:DSVR-derived TLV values have high correlation with the 2D-based measurements but with a consistently lower volume; bias -1.44cm3 [95% limits: -2.6 to -0.3] with improved resolution able to exclude hilar structures even in severe motion corruption or in cases of lung hypoplasia. Conclusions:Application of DSVR for fetal MRI provides a solution for analysis of motion corrupted scans and does not suffer from the interpolation error inherent in 2D-segmentation as per current clinical practice. It increases information content of acquired data in terms of visualising organs in 3D space and quantification of volumes, which we believe will have important value for counselling and surgical planning. Keywords:Fetal MRI; congenital diaphragmatic hernia; CPAM; lung volume

The water content is a crucial factor in evaluating the causes of Benggang collapse. The soil–water characteristic curve (SWCC) is an important parameter for the quantitative study of soil water content. However, limited research has been carried out on the SWCCs of the Benggang soil profile. We studied two typical collapsing gullies in southeast China and conducted desorption experiments using a pressure plate extractor to analyze the SWCCs of the undisturbed soils of collapsing walls. The results show large variations in the SWCCs for different soil horizons of a collapsing wall that can be accurately fitted by the van Genuchten (VG) model (NSE≥0.90). With increasing soil depth, the a and θs parameters of the VG model first decrease and then increase, red soil layer had the highest a and θs (the average value of 0.046 and 0.369, respectively), whereas the n parameter of the VG model exhibits the opposite trend, sand soil layer had the highest n (the average value of 1.563). The θr parameter of the VG model decreases with increasing soil depth, red soil layer had the highest θr (the average value of 0.194). The red soil layer has the highest water-holding capacity, whereas the sandy soil and detritus layers have lower water-holding capacities. The SWCCs are related to the soil material composition, particle composition and porosity. The gravel content and the particle morphology (the aspect ratio, sphericity, and specific surface area) are also the significant influence factors for the SWCC that cannot be neglected. The difference among the SWCCs for the soil profiles of collapsing walls can be used to explain the mechanism for the collapse of collapsing wall. The results of this study provide a theoretical basis for understanding the process of the collapse of collapsing wall in Benggang in southeast China.

Objective: To test the predictive value of the Physiological Breech Birth Algorithm. Design: Retrospective case-control study Setting: Teaching Hospital, United Kingdom Population/sample: Cases were all vaginal breech births >37 weeks’ gestation where neonatal admission or death occurred between April 2012 and April 2020. Controls were the two term breech births without admission immediately prior to the cases. Methods: Data was collected from intrapartum care records and analysed using SPSS v26 statistical software. The chi-square test was used to determine association between exposure to the variables of interest and admission to the neonatal unit. Multiple logistic regression was used to test the predictive value of delays defined as non-adherence to the Algorithm. Main outcome measures: Intervals between the start of labour, the start of second stage of labour and various stages of emergence (presenting part, buttocks, pelvis, arms, head). Results: Logistic regressing modelling using the Algorithm time frames had an 84.2% accuracy, a sensitivity of 66.7% and a specificity of 92.3%. Delays between umbilicus and head >3 minutes (OR: 9.508 [95% CI: 1.390-65.046] p=0.022) and from buttocks on the perineum to head >7 minutes (OR: 6.682 [95% CI: 0.940-41.990] p=0.058) showed the most effect. Lengths of time until the first intervention were also longer among the cases, suggesting that at least some of this delay is modifiable. Conclusions: Improved recognition of delay and efficient assistance may help improve vaginal breech birth outcomes. Further research should determine whether training based on the Physiological Breech Birth Algorithm can reduce neonatal admissions.

Introduction: The Atricure EPi-Sense Device is used for the hybrid convergent procedure, an emerging treatment for persistent atrial fibrillation and long standing persistent atrial fibrillation. However, data on the AE related to the EPi-Sense device are scarce. Methods: Keyword “EPI-SENSE” was searched on the MAUDE database. There were 80 device reports from 2016-2020. After excluding reports when the device was not returned for evaluation, 79 device reports were included for final analysis. Results: The adverse events were broadly classified into 11 categories. The most common complications were pericardial effusion (25.3%), stroke (17.7%) and atrio-esophageal fistula (AEF) (8.9%). Death was reported in 15 (19%) cases, 3 of which were due to pulmonary embolism, 6 due to AEF, 3 due to unknown cause, 1 due to sepsis, 2 due to events related to acute renal failure (ARF). Discussion: Pericardial effusion is a common AE reported in patients with convergence procedure and is well documented in the CONVERGE trial. Convergent procedure is unique in that the epicardial ablations are performed on the posterior wall with the radiofrequency probe directed towards the heart and away from the esophagus which in theory should reduce esophageal injuries. Despite that, a high number of AEF were noticed. Lastly, there were also some reports of saline perfusion malfunction which can lead to injuries due to overheating. Conclusion: This analysis of the AE related to the EPi-Sense device highlights several major adverse events that are previously unreported.

Introduction: Utilizing a 3-dimensional (3-D) mapping system and intracardiac echocardiography (ICE) has allowed ablation procedures with less or without fluoroscopy; however, there is limited data for patients with cardiac electronic implantable device (CIED) leads regarding the suspected risk of lead injury. Therefore, we sought to explore technics to perform safe trans-septal approach and catheter manipulation technique in patients with CIED leads. Methods and Results: This study comprised 68 consecutive patients (45 [66.2%] males, median [interquartile range] 73 [68–77] years old) with CIED who underwent catheter ablation for supraventricular tachycardia, 16 without fluoroscopy (zero-fluoro group) and 52 with fluoroscopy (conventional-fluoro group), between July 2019 and April 2021. All procedures were performed under a 3-D mapping system and ICE guidance. We compared the differences in treatment and development of complications between the two groups. The procedures were mainly atrial fibrillation (73.6%) and atrial tachycardia. The median time from venipuncture to trans-septal procedure (zero-fluoro vs. conventional-fluoro group: 27.0 min vs. 23.5 min, P=0.71) and total procedure time (215 min vs. 172 min, P=0.55) were not different between the two groups. The acute procedural success rate (100% vs. 98.1%, P=1.00) and reduction of atrial high-rate episodes at 6 months (3.2 [0.3–93.9]% vs. 1.0 [0.0–14.9]%, P=0.33) did not differ between the two groups. No patient showed lead-related complications in both groups. Conclusions: Zero-fluoro ablation for supraventricular arrhythmia using 3-D mapping and ICE in patients with CIED leads was feasible under careful catheter manipulation.

There is increasing attention being given toward social and ethical implications of xenotransplantation that may begin relatively soon. IN a recent commentary by Loebe and Parker, the authors address many of the social and ethical issues in regard to xenotransplantation, but do so only superficially. This letter to the editor responds to many of the points they raise.

Amyloid beta (Aβ) peptides, a major contributor to Alzheimers disease, occur in differing lengths, each of which forms a multitude of assembly types. The most toxic soluble oligomers are formed by Aβ42; some of which have antiparallel β-sheets. Previously, our group proposed molecular models of Aβ42 hexamers in which the C-terminus third of the peptide (S3) forms an antiparallel 6-stranded β-barrel that is surrounded by an antiparallel barrel formed by the more polar N-terminus (S1) and middle (S2) portions. These hexamers were proposed to act as seeds from which dodecamers, octadecamers, both smooth and beaded annular protofibrils, and transmembrane channels form. Since then, numerous aspects of our models have been supported by experimental findings. Recently, NMR-based structures have been proposed for Aβ42 tetramers and octamers, and NMR studies have been reported for oligomers composed of ~ 32 monomers. Here we propose a range of concentric β-barrel models and compare their dimensions to image-averaged electron micrographs of both beaded annular protofibrils (bAPFs) and smooth annular protofibrils (sAPFs) of Aβ42. The smaller oligomers have 6, 8, 12, 16, and 18 monomers. These beads string together to form necklace-like bAPFs. These gradually morph into sAPFs in which a S3 β-barrel is shielded on one or both sides by β-barrels formed from S1 and S2 segments.

Dynamics of protein cavities associated with protein fluctuations and conformational plasticity is essential for their biological function. NMR ensembles, Molecular Dynamics (MD) simulations combined with Principal Component Analysis (PCA), and Normal Mode Analysis (NMA) provide appropriate frameworks to explore functionally relevant protein dynamics and cavity changes relationships. Within this context, we have developed ANA (Analysis of Null Areas), an efficient method to calculate cavity volumes. ANA is based on a combination of algorithms that guarantees its robustness against numerical differentiations. This is a unique feature with respect to other methods. Herein, we test ANA as a biophysical and bioinformatic method to analyze different structural and dynamics properties of cavities. In order to address this task, we have developed an updated and improved version of ANA that expands it use to quantify changes in cavity features, like volume and flexibility, due to protein structural distortions performed on predefined biologically relevant directions, e.g, directions of largest contribution to protein fluctuations (PCA modes) obtained by MD simulations or ensembles of NMR structures, collective NMA modes or any other direction of motion associated with specific conformational changes. A web page has been developed and its facilities are explained in detail, making the software available to all users. Firstly, we show that ANA can be useful to explore gradual changes of cavity volume and flexibility associated with protein ligand binding. Secondly, we perform a comparison study of the extent of variability between protein backbone structural distortions, and changes in cavity volumes and flexibilities evaluated for an ensemble of NMR active and inactive conformers of the epidermal growth factor receptor (EGFR) structures. Finally, we compare changes in size and flexibility between sets of NMR structures for different homologous chains of dynein.

Diabetes mellitus and high levels of resistin are risk factors for COVID-19, suggest- ing a shared mechanism for their contribution to the increased severity of COVID-19. Resistin belongs to the family of resistin-like molecules (RELMs) whose implications for inflammatory and metabolic dysfunctions warrant its study in order to shed light on the etiology of these concerning pathologies. In this work, our objective is to char- acterize the structural dynamics of the reported crystallized resistin-like molecules. We performed molecular dynamics simulations of all-atom solvated protein at physiological and high temperatures for the three mouse structures reported so far. We found that in all the structures studied, there is a loss of helicity as a first step of protein denat- uration. There is a high stability of the globular β-sheet domain in resistin protein structures that is not conserved for RELMβ. At high temperature, we found a partial interconversion of α-helices into β-sheets in all proteins, indicating that this propensity is not only found during aggregation but also heating. We had been able to identify a largely persistent hydrogen-bond network shared by all the proteins in the interchain globular domain at room temperature. This network of hydrogen bonds is conserved considerably at high temperature in resistin structures, but not in RELMβ. These findings may guide future studies to increase our understanding of the different and shared mechanisms of action of RELMs.

Division of labour occurs when cooperating individuals specialise to perform different tasks. In bacteria and other microorganisms, some species divide labour by random specialisation, where an individual’s role is determined by random fluctuations in biochemical reactions within the cell. Other species divide labour by coordinating across individuals to determine which cells will perform which task, using mechanisms such as between-cell signalling. However, previous theory, examining the evolution of mechanisms to divide labour between reproductives and sterile helpers, has only considered clonal populations, where there is no potential for conflict between individuals. We used a mixture of analytical and simulation models to examine non-clonal populations and found that: (1) intermediate levels of coordination can be favoured, between the extreme of no coordination (random) and full coordination; (2) as relatedness decreases, coordinated division of labour is less likely to be favoured. Our results can help explain why coordinated division of labour is relatively rare in bacteria, where groups may frequently be non-clonal.

This paper is devoted to the mathematical modeling of a combined effect of directional and bulk crystallization in a phase transition layer with allowance for nucleation and evolution of newly born particles. We consider two models with and without fluctuations in crystal growth velocities, which are analytically solved using the saddle-point technique. The particle-size distribution function, solid-phase fraction in a supercooled two-phase layer, its thickness and permeability, solidification velocity, and desupercooling kinetics are defined. This solution enables us to characterize the mushy layer composition. We show that the region adjacent to the liquid phase is almost free of crystals and has a constant temperature gradient. Crystals undergo intense growth leading to fast mushy layer desupercooling in the middle of a two-phase region. The mushy region adjacent to the solid material is filled with the growing solid phase structures and is almost desupercooled.

Background: Presently, there are limited reports in the literature on the post-operative (mid-term) clinical outcome for pure Aortic Regurgitation (AR) following Transcatheter Aortic Valve Replacement (TAVR). Methods: Between March 2014 and June 2019, a total of 134 high-risk patients with pure, symptomatic severe AR patients were enrolled in the current study. The outcome was assessed according to the VARC-2 criteria. Procedural results, clinical outcomes, and the patients’ hemodynamics for a period of 1-year were analyzed. Results: Patient mean was 73.1±6.4 years and 25.4% were female. The average STS score was 9.8+5.3%. Procedural success was 97.1% (130/134), and the device success rate was 96.3% (129/134). Five cases were converted to open surgery, while two patients underwent valvular reinterventions (surgical aortic valve replacement for thrombosis and increasing paravalvular regurgitation). The mean aortic valve gradient was 10.2±4.1 mmHg, while the moderate and severe aortic regurgitation was 1.6% at 1 year. Paravalvular regurgitation was none/trivial in 79.8% and mild in 18.5%. The 1-year all-cause mortality rate was 7.4%. At 1-year, the stroke incidence rate was 2.2%. And pacemaker was implanted in 8.9% of the enrolled patients. Conclusions: In high-risk patients undergoing transapical-TAVR for AR, the use of the J-Valve is safe and effective TAVR should be considered as a reasonable option for high-risk patients with pure AR.

Cannabinoids biosynthesis in phytoplankton has attracted much attention due to the rapid development of genetic tools and the optimization of genetic transformation methods in microalgae. To monitor the biosynthesis process, proper sample preparation and practical instrumental methods are needed to measure the various precursors, intermediates, cannabinoids, and their degradation products. The objective of this study was to develop a sample preparation procedure for the quantification of olivetolic acid (OA), cannabigerolic acid (CBGA), cannabidiolic acid (CBDA), tetrahydrocannabinolic acid (THCA), olivetol (OL), cannabidiol (CBD), and tetrahydrocannabinol (THC) using single-quadrupole gas chromatography-mass spectrometry (GC-MS). Isochrysis galbana was used as the model matrix. After methanol extraction, samples were purified using solid phase extraction (SPE), silylated with N-methyl-N-(trimethylsilyl)trifluoroacetamide, and analyzed using GC-MS in electron ionization mode. A strong anion-exchange SPE efficiently recovered OA, CBGA, CBDA, and THCA. A graphitized carbon black SPE was necessary to purify OL, CBD, and THC. Both columns removed amino acids, sugars, polyols, and pigments from the algae extract and prepared samples that are suitable for silylation and GC-MS analysis. The total protocol, including solvent extraction, SPE, silylation, and GC-MS analysis, was validated in accordance with the ICH guidelines. Performance characteristics of our method are superior to existing protocols with similar complexity in the literature.

Objectives Flexible endoscopy (FE) assessed the whole approachable aeroesophageal (AE) tracks and changes of management in infants with severe bronchopulmonary dysplasia (sBPD). Methods A 10 years (2011-2020) retrospective study of sBPD infants who had FE with and without artificial airway in AE tracks. FE with noninvasive ventilation (FE-NIV) of pharyngeal oxygen with nose-close and abdomen-compression was supported. Data of found pathologies, changes of consequent management and therapeutic interventions were collected and analyzed. Results Total 42 infants enrolled. Two scopes of 1.8mm and 2.6mm were used. FE revealed 129 AE pathologies in 38 (90.5%) infants. Twenty-eight (66.7%) infants detected more than one lesion. In 35 (83.3%) infants with 111 airway lesions, bronchial granulations (28, 25.2%), tracheomalacia (18, 16.2%) and bronchial granulations (15, 13.5%) were the leadings. Fifteen (35.7%) infants had 18 esophageal lesions. No significant FE-NIV complication noted. FE findings resulted consequent changes of management in all 38 infants. Thirty-six (85.7%) infants involved respiratory care of pressure titrations (29, 45.3%), shorten suctioning depth (17, 26.6%), changed endotracheal or tracheostomy tube depth (10, 15.6%) and extubation (8, 12.5%). Twenty-one (50%) infants had 50 medication changes included add steroids, anti-reflux medicine, antibiotics and stop antibiotics. Eighteen (42.8%) infants had received 37 therapeutic FE-NIV procedures which included 14 balloon dilatation, 13 laser-plasty and 10 stent implantations. Seven (16.7%) infants had surgeries included 4 tracheostomies and 3 fundoplications. Conclusion FE-NIV can be a safe and valuable modality for direct visual assessment of AE pathologies which contributed subsequent changes of clinical management in sBPD infants.

Synthetic biology, an emerging research field, can promote biomanufacturing by offering various efficient chassis. Engineering Bacillus subtilis, an important workhorse in industrial biotechnology, through synthetic biology approaches may be a disruptive innovation. Advancements in chassis engineering, a synthetic biology strategy for genome-reduced cell factories, cell-free systems, and synthetic microbial consortia would be a driving force facilitating microbial production. We discussed chassis engineering categories and applications for B. subtilis. Prospects and challenges for chassis engineering in B. subtilis were also analyzed in this review article.

Aim Implementation of a web-form based pharmacovigilance plan for the spontaneous notification of adverse events to the Comirnaty® COVID-19 vaccine during its administration to hospital healthcare professionals. Methods An electronic pharmacovigilance form was developed containing 8 pre-defined event options, an open answer option for the description of other events and/or symptoms, and a question about the overall intensity of symptoms. The adverse events reports were standardised according to physiological and pathological condition. Results A total of 4119 adverse events notifications were obtained with a 45% rate of electronic notification. The most clinically relevant events reported were: tachycardia (n=19), dyspnoea (n=7), chest pain (n=6), facial/labial oedema (n=6), lipothymia (n=5), bronchospasm (n=2), herpetic infection (n=2), vasculitis (n=2), arrhythmia (n=1), difficult to control arterial hypertension (n=1), gastritis (n=1) and spontaneous abortion (n=1). Regarding the intensity of symptoms (n=2928), 70.0% were reported as mild, 25.8% as moderate and 4.27% as severe, with higher intensity in the 2nd dose compared to 1st dose. The highest frequency of severe events were reported in the groups from 40 to 59 years in both vaccination periods. During the vaccination process, no hospitalisations and no deaths were notified and/or recorded. Conclusion In this real world study, comparing with Comirnaty clinical trials program, it was observed a higher frequency of adenomegaly and gastrointestinal disorders. Noteworthy, the notification of a case of miscarriage. The use of hospital pharmacy pharmacovigilance electronic forms, seemed to be relevant to notification adherence and to obtain a greater and faster knowledge of COVID-19 vaccine safety profile.

Wild equids can harvest multiple-host infectious agents that are able to affect other wildlife species, but also domestic animals and humans. The contact between wild and domestic equids is constantly increasing due to the depletion of natural areas, climate and land-usage changes, which could result in burdensome epidemics. Nevertheless, currently there is a lack of adequate epidemiological data from zebra. Three electronic databases were searched from 10 to 20 March 2021 for publications reporting bacterial, viral and protozoan infections in zebra. Data for a total of 12 nominal variables were extracted from reviewed papers to undergo a qualitative analysis on microbial infections in zebra. Prevalence-reporting studies were subjected to meta-analysis for estimating the pooled prevalence and seroprevalence of infectious agents in wild zebra populations. We identified 29 pathogen species and the most represented were Equine Herpesvirus 1 and 9, Bacillus anthracis, African Horse Sickness virus and Theileria equi. They were reported from all the three zebra species, both in captivity and wilderness. Pooled seroprevalences were estimated for the equine Orbiviruses AHSV (70%; 95%CI: 35-96%) and EEV (21%; 95%CI: 8-38%) and for the equine α -Herpesviruses EHV-1 (72%; 95%CI: 43-93%), EHV-4 (40%; 95%CI: 0-100%) and EHV-9 (58%; 95%CI: 9-98%), and pooled prevalences for the equine piroplasms T. equi (100%; 95%CI: 94-100%) and B. caballi (8%; 95%CI: 0-28%). Zebra is most probably a reservoir from which AHSV, EHV-1 and T. equi can be transmitted to horse populations, potentially causing disastrous epidemics. Zebra can also harvest zoonotic pathogens like B. anthracis, A. phagocytophylum, CCHFV and T. brucei. Other agents like EHV-9, BPV-1 and BPV-2 have the potential to spread from zebra to other wild endangered animal species. We conclude that zebra is an important host for multiple and dangerous pathogens. Alert and epidemiological research should be increased on infectious agents of zebra.

Objective. To systematically review the evidence from randomised controlled trials evaluating the effects of goal oriented care against standard care for multimorbid adults. Data sources/Study setting. Existing literature presenting the resulto of randomized trials assessing the outcome of goal oriented care compared with usual care for adults with multimorbidity. Study design. Systematic review and meta-analysis. Data collection/Extraction methods. We searched the Cochrane Database of Systematic Reviews (CENTRAL), EMBASE, MEDLINE, CINHAL, trial registries such as ClinicalTrial.gov and World Health Organizational International Clinical Trials Registry Platform (ICTRP) and the references of eligible trials and relevant reviews. Goal-oriented care was defined by the following: goal setting at the individual level; collaborative identification of goals; valuing and using the individuals’ resources and skills combined with the medical standpoint; full entitlement of the person in the goal choice. A total of 197 studies were reviewed. Ten trials were included. We extracted outcome data on quality of life, hospital admission, patients’ satisfaction, patient and caregiver burden. Risk of bias was assessed and certainty of evidence was evaluated using GRADE.. Principal findings. No study was found fully free of bias. No effect was found on quality of life (Standardized Mean Difference (SMD) 0.10; 95% CI -0.06 to 0.26) and hospital admission (Risk Ratio (RR): 0.87; 95% CI 0.65 to 1.17). A very small effect was observed for patients’ satisfaction (SMD: 0.15; 95% CI 0.00 to 0.29) and caregiver burden (SMD -0.13; 95%CI -0.26 to 0.00). Certainty of evidence was low for all outcomes. Conclusions Despite its sound rationale and the strong push towards its dissemination, the results of this meta-analysis prevent to reach firm conclusions about effects of goal-oriented care. Future research should overcome the shortcomings of studies assessed in this meta-analysis. A sound application of the indications for research of complex healthcare interventions is warranted.

Background: Cardiac Implantable Electronic Devices (CIED) include pulse generators and leads. In some implanting centres, it is common practice to combine devices with leads from different companies. Case series have reported episodic high-impedance changes in Boston Scientific CIEDs with competitor leads. We investigated the incidence of high-impedance abnormalities in matched vs. mismatched Boston Scientific CIEDs. Methods: Retrospective chart review identified all consecutive Boston Scientific Accolade pacemakers and Autogen implantable cardioverter defibrillators (ICD) implanted between January 2017 and June 2019 at a Canadian tertiary care centre. The primary outcome was the occurrence of transient, high-impedance changes which resulted in a switch to unipolar pacing / sensing in the absence of any other identifiable lead issue. Fisher exact tests (two-tailed, α = 0.05) were used to compare the incidence of outcomes in matched vs. mismatched systems. Results: 564 Boston Scientific CIEDs were identified associated with 969 individual leads. The primary outcome occurred with 22 leads (21 Medtronic and 1 Abbott), associated with occasional pacing inhibition, syncope, and/or early surgical revision. Mismatched systems were significantly associated with CIED malfunction compared to matched systems (3.4% vs. 0%, P = 0.0001). Median time from implant to unipolar safety switch was 19.3 months. Median follow-up time was 21.6 months. Conclusion: Use of mismatched leads with a Boston Scientific Accolade or Autogen device was associated with increased system malfunction and adverse clinical outcomes. Awareness of this interaction can allow for institution of appropriate programming remedies and may increase scrutiny of the use of mismatched CIED systems.

The analysis of large samples of hydrologic catchments is regularly used to gain understanding of hydrologic variability and controlling processes. Several studies have pointed towards the problem that available catchment descriptors (such as mean topographic slope or average subsurface properties) are insufficient to capture hydrologically relevant properties. Here, we test the assumption that catchment location, i.e. the relative properties of catchments in relation to their surrounding neighbours, can provide additional information to reduce this problem. We test this idea in the context of Great Britain for a widely discussed problem, that of catchment water balance errors due to subsurface losses. We test three hypotheses while considering different locational aspects (1) location to coast, (2) location next a relevant neighbour and (3) location within the drainage basin, utilizing only basic and widely available geological and topographical information. We find that subsurface losses from catchments with a highly permeable geology connection to the coast are in order of 20% water balance error. We define a simple topographic-geologic index that is able to partially explain water balance issues between neighbours of highly permeable catchments. The results imply that location, geology and topography combine to define the differences of water balances of UK catchments compared to what we would expect from their climatic setting alone. The simple index defined here can easily be derived globally and tested regarding its wider applicability.

Snow cover area on a river basin, affects so many meteorologic and environmental parameters. By growing remote sensing technology, nowadays snow cover area could be measured on a regular basis for scientific purposes. In this study, the monthly average of snow cover area of the Baranduz river basin from West Azerbaijan in Iran had been used for modelling by ANN and SVM. The snow cover area was extracted from MODIS 8-day maximum snow extent products from 2000 to 2019. Also, the 20 meteorologic parameters were collected from Bibakran and Babarud ground hydrometeorological stations and 20 parameters were collected from satellite base data powered by NASA LaRC projects. After BoxCox transformation analysis, the feature selection methods were used to select the modelling subsets. Partial least square regression base filter and wrapper feature selection methods were used to select modelling subsets. LW, RC, SR, VIP, SMC, MRMR, JT filter methods and GA, MCUVE and REP wrapper methods were used to select the best parameters for modelling. By increasing the thresholds of the feature selection methods, the number of the selected parameters in subsets was decreased, and after a certain amount of thresholding value, the number of parameters was fixed in 10 variables. Selected subsets were being evaluated by multicollinearity indexes and by performances of the ANN and the SVM models. 80% of the data used for training models and 20% of the data used for testing the models. The accuracy of all models was high and acceptable but, in some subsets, there was a serious multicollinearity issue. However, the correlation between parameters was so high despite this, the PLSR base feature selection methods have been very successful in reducing a great amount of multicollinearity in selected subsets. Also, the ANN and SVM models have shown very high performance in modelling the monthly snow cover area.

Objective :The purpose of this research is to explore the clinical application prospect of percutaneous closure atrial septal defects guided by thoracic echocardiography. Methods : Selected 90 inpatients who were pure atrial septal defects from sep 2014 to December 2019, Under local anesthesia via femoral vein puncture closure atrial septal defects guided by thoracic echocardiography, Real-time evaluatie plugging result.The patients underwent follow-up echocardiography at 3 days, 3 months, 6 months, 12 months after surgery．Results Intraoperative occlusion was not successful in 3 cases（The plug is not fixed firmly, so withdraw the plug）， Occluder were successfully implanted in 87 patients, there were no serious complications such as valvular injury、pericardial effusion、occluder off,five patients had a little residual shunt in 3 days after surgery, residual shunt disapper after 3 months underwent follow-up echocardiography, the rest of the patients does not appear residual shunt.. Conclusion :Percutaneous closure atrial septal defects guided by thoracic echocardiography had Superiority such as simplicity of operator、shorter operator time、less-injury、safety、fast recovery,the surgery has a broad clinic prospects．

Electrical storm can be caused by structural heart diseases and/or functional electrical abnormalities. We report a young boy without cardiac risk factors, having a positive family history of sudden cardiac death who presented with electrical storm. Stepwise diagnostic approach was not fruitful to determine previously known causes as the origin of the electrical storm. A new genotype related to the current electrical storm has been found, and intracardiac pacing ceased it.

Background and Purpose: Despite availability of a variety of treatment options, many asthma patients have poorly controlled disease with frequent exacerbations. Proteinase-activated receptor-2 (PAR2) has been identified in pre-clinical animal models as important to asthma initiation and progression following allergen exposure. Proteinase activation of PAR2 induces intracellular Ca2+, mitogen activated protein kinase (MAPK) and -arrestin signaling the airway, leading to both inflammatory and protective effects. We have developed C391, a potent PAR2 antagonist effective in blocking peptidomimetic- and trypsin-induced PAR2 signaling in vitro as well as reducing inflammatory PAR2-associated pain in vivo. We hypothesized that PAR2 reduction with C391 would attenuate allergen-induced asthma indicators in murine models. Experimental Approach: We evaluated the ability for C391 to alter Alternaria alternata-induced PAR2 signaling pathways in vitro using a human airway epithelial cell line that naturally expresses PAR2 (16HBE14o-) and a transfected embryonic cell line (HEK 293). We next evaluated the ability for C391 to reduce A. alternata-induced asthma indicators in vivo in two murine strains. Key Results: C391 blocked A. alternata-induced, PAR2-dependent Ca2+ and MAPK signaling in 16HBE14o- cells, as well as -arrestin recruitment in HEK 293 cells. C391 effectively attenuated A. alternata-induced inflammation, mucus production, mucus cell hyperplasia and airway hyperresponsiveness in acute asthma murine models. Conclusions and Implications: To our knowledge, this is the first demonstration of pharmacological intervention of PAR2 to reduce allergen-induced asthma indicators in vivo. These data support further development of PAR2 antagonists as potential first-in-class allergic asthma drugs.