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Ambitious methane (CH4) emission mitigation represents one of the most effective opportunities to slow the rate of global warming over the next decades. The oil and gas (O&G) sector is a significant source of methane emissions, with technically feasible and cost-effective emission mitigation options. Romania, a key O&G producer within the EU, with the second highest reported annual CH4 emissions from the energy sector in the year 2020 (Greenhouse Gas Inventory Data - Comparison by Category, 2022), can play an important role towards the EU's emission reduction targets. In this study, we quantify CH4 emissions from onshore oil production sites in Romania at source and facility level using a combination of ground- and drone-based measurement techniques. Measured emissions were characterized by heavily skewed distributions, with 10 % of the sites accounting for more than 70 % of total emissions. Integrating the results from all site-level quantifications with different approaches, we derive a central estimate of 5.4 kg h−1 per site of CH4 (3.6 %–8.4 %, 95 % confidence interval) for oil production sites. This estimate represents the third highest when compared to measurement-based estimates of similar facilities from other production regions. Based on our results, we estimate a total of 120 kt CH4 yr−1 (range: 79–180 kt yr−1) from oil production sites in our studied areas in Romania. This is approximately 2.5 times higher than the reported emissions from the entire Romanian oil production sector for 2020. Based on the source-level characterization, up to three-quarters of the detected emissions from oil production sites are related to operational venting. Our results suggest that O&G production infrastructure in Romania holds a massive mitigation potential, specifically by implementing measures to capture the gas and minimize operational venting and leaks.

Background: Transcriptional dysregulation, possibly affected by genetic variation, contributes to disease development. Due to dissimilarities in development, function, and remodeling during disease progression, transcriptional differences between the left atrial (LA) and right atrial (RA) may provide insight into diseases such as atrial fibrillation., Methods: Lateral differences in atrial transcription were evaluated in CATCH ME (Characterizing Atrial fibrillation by Translating its Causes into Health Modifiers in the Elderly) using a 2-stage discovery and replication design. The design took advantage of the availability of 32 paired samples, for which both LA and RA tissue were obtained, as a discovery cohort, and 98 LA and 69 RA unpaired samples utilized as a replication cohort., Results: A total of 714 transcripts were identified and replicated as differentially expressed (DE) between LA and RA, as well as 98 exons in 55 genes. Approximately 50% of DE transcripts were colocated with another frequently correlated DE transcript ( P FDR ≤0.05 for 579 regions). These transcription disequilibrium blocks contained examples including side-specific differential exon usage, such as the PITX2 locus, where ENPEP showed evidence of differential exon usage. Analysis of this region in conjunction with BMP10 identified rs9790621 as associated with ENPEP transcription in LA, while rs7687878 was associated with BMP10 expression in RA. In RA, BMP10 and ENPEP were strongly correlated in noncarriers, which was attenuated in risk-allele carriers, where BMP10 and PITX2 expression were strongly correlated., Conclusions: These results significantly expand knowledge of the intricate, tissue-specific transcriptional landscape in human atria, including DE transcripts and side-specific isoform expression. Furthermore, they suggest the existence of blocks of transcription disequilibrium influenced by genetics.

Purpose: The need for an interval between the administration of long-acting Somatostatin Receptor Analogues (SSA) and the [ 68 Ga]Ga-DOTA-TATE PET has been questioned based on recent literature in the new EANM guidelines. Here an earlier studies showed that SSA injection immediately before SSTR PET had minimal effect on normal organ and tumor uptake (1). However, data are scarce and there are (small) differences between [ 68 Ga]Ga-DOTA-TATE and [ 68 Ga]Ga-DOTA-TOC binding affinity, and it remains unknown whether these findings can be directly translated to scans with [ 68 Ga]Ga-DOTA-TOC as well. The purpose of this study was to assess the effect of SSA use on the biodistribution in a subsequent [ 68 Ga]Ga-DOTA-TOC PET/CT and compare this intra-individually across several cycles of SSA treatments., Methods: Retrospectively, 35 patients with NENs were included. [ 68 Ga]Ga-DOTA-TOC PET at staging and after the 1st and 2nd cycle of SSA were included. SUVmean and SUVmax of blood, visceral organs, primary tumor and two metastases were determined. Also, the interval between SSA therapy and the PET scan was registered., Results: Treatment with SSA resulted in a significantly higher bloodpool activity and lower visceral tracer uptake. This effect was maintained after a 2nd cycle of SSA therapy. Furthermore, there was an inverse relationship between bloodpool tracer availability and visceral tracer binding and a positive correlation between bloodpool tracer availability and primary tumor tracer uptake. With an interval of up to 5 days, there was a significantly higher bloodpool activity than at longer intervals., Conclusion: Absolute comparison of the SUV on [ 68 Ga]Ga-DOTA-TOC PET should be done with caution as the altered biodistribution of the tracer after SSA treatment should be taken into account. We recommend not to perform a scan within the first 5 days after the injection of lanreotide., (© 2024. The Author(s).)

Background: Atrial cardiomyopathy (atCM) is an emerging prognostic factor in cardiovascular disease. Fibrotic remodeling, cardiomyocyte hypertrophy, and capillary density are hallmarks of atCM. The contribution of etiological factors and atrial fibrillation (AF) to the development of differential atCM phenotypes has not been quantified. This study aimed to evaluate the association between histological features of atCM and the clinical phenotype., Methods and Results: We examined left atrial (LA, n=95) and right atrial (RA, n=76) appendages from a European cohort of patients undergoing cardiac surgery. Quantification of histological atCM features was performed following wheat germ agglutinin/CD31/vimentin staining. The contributions of AF, heart failure, sex, and age to histological characteristics were determined with multiple linear regression models. Persistent AF was associated with increased endomysial fibrosis (LA: +1.13±0.47 μm, P =0.038; RA: +0.94±0.38 μm, P =0.041), whereas total extracellular matrix content was not. Men had larger cardiomyocytes (LA: +1.92±0.72 μm, P <0.001), while women had more endomysial fibrosis (LA: +0.99±0.56 μm, P =0.003). Patients with heart failure showed more endomysial fibrosis (LA: +1.85±0.48 μm, P <0.001) and extracellular matrix content (LA: +3.07±1.29%, P =0.016), and a higher capillary density (LA: +0.13±0.06, P =0.007) and size (LA: +0.46±0.22 μm, P =0.044). Fuzzy k-means clustering of histological features identified 2 subtypes of atCM: 1 characterized by enhanced endomysial fibrosis (LA: +3.17 μm, P <0.001; RA: +2.86 μm, P <0.001), extracellular matrix content (LA: +3.53%, P <0.001; RA: +6.40%, P <0.001) and fibroblast density (LA: +4.38%, P <0.001), and 1 characterized by cardiomyocyte hypertrophy (LA: +1.16 μm, P =0.008; RA: +2.58 μm, P <0.001). Patients with fibrotic atCM were more frequently female (LA: odds ratio [OR], 1.33, P =0.002; RA: OR, 1.54, P =0.004), with persistent AF (LA: OR, 1.22, P =0.036) or heart failure (LA: OR, 1.62, P <0.001). Hypertrophic features were more common in men (LA: OR=1.33, P =0.002; RA: OR, 1.54, P =0.004)., Conclusions: Fibrotic atCM is associated with female sex, persistent AF, and heart failure, while hypertrophic features are more common in men.

Objectives: To evaluate the role of P-wave parameters, as defined on preprocedural electrocardiography (ECG), in predicting atrial fibrillation after cardiac surgery [postoperative atrial fibrillation (POAF)]., Methods: PubMed, Cochrane library and Embase were searched for studies reporting on P-wave parameters and risk of POAF. Meta-analysis of P-wave parameters reported by at least 5 different publications was performed. In case of receiver operator characteristics (ROC-curve) analysis in the original publications, an ROC meta-analysis was performed to summarize the sensitivity and specificity., Results: Thirty-two publications, with a total of 20 201 patients, contributed to the meta-analysis. Increased P-wave duration, measured on conventional 12-lead ECG (22 studies, Cohen's d = 0.4, 95% confidence interval: 0.3-0.5, P < 0.0001) and signal-averaged ECG (12 studies, Cohen's d = 0.8, 95% confidence interval: 0.5-1.2, P < 0.0001), was a predictor of POAF independently from left atrial size. ROC meta-analysis for signal-averaged ECG P-wave duration showed an overall sensitivity of 72% (95% confidence interval: 65-78%) and specificity of 68% (95% confidence interval: 58-77%). Summary ROC curve had a moderate discriminative power with an area under the curve of 0.76. There was substantial heterogeneity in the meta-analyses for P-wave dispersion and PR-interval., Conclusions: This meta-analysis shows that increased P-wave duration, measured on conventional 12-lead ECG and signal-averaged ECG, predicted POAF in patients undergoing cardiac surgery., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

In human cardiology, the anatomical origin of atrial premature depolarizations (APDs) is derived from P wave characteristics on a 12-lead electrocardiogram (ECG) and from vectorcardiography (VCG). The objective of this study is to differentiate between anatomical locations of APDs and to differentiate APDs from sinus rhythm (SR) based upon VCG characteristics in seven horses without cardiovascular disease. A 12-lead ECG was recorded under general anaesthesia while endomyocardial atrial pacing was performed (800−1000 ms cycle length) at the left atrial free wall and septum, right atrial free wall, intervenous tubercle, as well as at the junction with the cranial and caudal vena cava. Catheter positioning was guided by 3D electro-anatomical mapping and transthoracic ultrasound. The VCG was calculated from the 12-lead ECG using custom-made algorithms and was used to determine the mean electrical axis of the first and second half of the P wave. An ANOVA for spherical data was used to test if the maximal directions between each paced location and the maximal directions between every paced location and SR were significantly (p < 0.05) different. Atrial pacing data were not available from the LA septum in three horses, the intervenous tubercle in two horses, and from the LA free wall in one horse. The directions of the maximal electrical axes showed significant differences between all paced locations and between the paced locations and SR. The current results suggest that VCG is useful for identifying the anatomical origin of an atrial ectopy.

In human cardiology, the anatomical origin of ventricular premature depolarizations (VPDs) is determined by the characteristics of a 12-lead electrocardiogram (ECG). Former studies in horses had contradictory results regarding the diagnostic value of the 12-lead ECG and vectorcardiography (VCG), which results were attributed to the different cardiac conduction system in this species. The objective of this study was to determine if the anatomical origin of pacing-induced VPDs could be differentiated in horses based upon VCG characteristics. A 12-lead ECG was recorded in seven horses under general anesthesia while right and left ventricular endomyocardial pacing was performed (800−1000 ms cycle length) at the apex, mid and high septum and mid and high free wall, and at the right ventricular outflow tract. Catheter positioning was guided by 3D electro-anatomical mapping and echocardiography. A median complex, obtained from four consecutive complexes, was calculated for each pacing location and sinus rhythm. The VCG was calculated from the 12-lead ECG-derived median complexes using custom-made algorithms and was used to determine the initial and maximum electrical axes of the QRS complex. An ANOVA for spherical data was used to test if VCGs between each paced location and between pacing and sinus rhythm were significantly (p < 0.05) different. The model included the radius, azimuth and elevation of each electrical axis. Pacing induced significantly different initial and maximum electrical axes between different locations and between pacing and sinus rhythm. The current results suggest that VCG is a useful technique to identify the anatomical origin of ventricular ectopy in horses.

The imbalance between production and clearance of amyloid β (Aβ) peptides and their resulting accumulation in the brain is an early and crucial step in the pathogenesis of Alzheimer's disease (AD). Therefore, Aβ is strongly positioned as a promising and extensively validated therapeutic target for AD. Investigational disease-modifying approaches aiming at reducing cerebral Aβ concentrations include prevention of de novo production of Aβ through inhibition of β-site amyloid precursor protein cleaving enzyme 1 (BACE1), and clearance of Aβ deposits via passive Aβ immunotherapy. We have developed a novel, high affinity antibody against Aβ peptides bearing a pyroglutamate residue at amino acid position 3 (3pE), an Aβ species abundantly present in plaque deposits in AD brains. Here, we describe the preclinical characterization of this antibody, and demonstrate a significant reduction in amyloid burden in the absence of microhemorrhages in different mouse models with established plaque deposition. Moreover, we combined antibody treatment with chronic BACE1 inhibitor treatment and demonstrate significant clearance of pre-existing amyloid deposits in transgenic mouse brain, without induction of microhemorrhages and other histopathological findings. Together, these data confirm significant potential for the 3pE-specific antibody to be developed as a passive immunotherapy approach that balances efficacy and safety. Moreover, our studies suggest further enhanced treatment efficacy and favorable safety after combination of the 3pE-specific antibody with BACE1 inhibitor treatment., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

The DEK oncoprotein regulates cellular chromatin function via a number of protein-protein interactions. However, the biological relevance of its unique pseudo-SAP/SAP-box domain, which transmits DNA modulating activities in vitro, remains largely speculative. As hypothesis-driven mutations failed to yield DNA-binding null (DBN) mutants, we combined random mutagenesis with the Bacterial Growth Inhibition Screen (BGIS) to overcome this bottleneck. Re-expression of a DEK-DBN mutant in newly established human DEK knockout cells failed to reduce the increase in nuclear size as compared to wild type, indicating roles for DEK-DNA interactions in cellular chromatin organization. Our results extend the functional roles of DEK in metazoan chromatin and highlight the predictive ability of recombinant protein toxicity in E. coli for unbiased studies of eukaryotic DNA modulating protein domains., (© 2021 Federation of European Biochemical Societies.)

Alum sludge, an Al-oxyhydroxide rich waste product from water treatment practices, has the potential to be valorized as a P adsorbent material. However, several challenges currently prevent its application as an adsorbent in industrial setting, i.e. a limited P adsorption capacity due to saturation by organic matter and a fine nature resulting in percolation problems in adsorption bed setups. In this study, granulation and subsequent calcination of alum sludge were proposed to overcome these issues and to improve the P adsorption properties of alum-based adsorbent (ABA) materials. The effect of calcination temperature on the physicochemical properties of granular material was examined using X-ray diffraction, mass-spectroscopy coupled thermogravimetric analysis, Fourier-transform infrared spectrometry and specific surface area analysis, combined with density and crushing strength measurements. The ABA material obtained at 550 °C showed superior P adsorption properties and, therefore, this material was selected for further P adsorption testing and characterization (scanning electron microscopy and sieving). Batch P adsorption tests showed that this material had a maximum P adsorption capacity of 7.27 mg-P g -1 . Kinetic adsorption tests determined the effect of the solid-to-liquid ratio and the granule particle size on the P removal. Finally, the performance of the ABA-550 material was tested in a pilot-scale adsorption setup, using a surface water stream (0.47 mg-P L -1 ) at a flow rate of 200 L h -1 . During the test, the P removal efficiency always exceeded 86%, while the material maintained its structural stability. The results of this study illustrate the potential of granulated/calcined ABA materials for P adsorption, paving the way for the industrial application of this novel, sustainable P removal technology., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Multiple animal models have been created to gain insight into Alzheimer's disease (AD) pathology. Among the most commonly used models are transgenic mice overexpressing human amyloid precursor protein (APP) with mutations linked to familial AD, resulting in the formation of amyloid β plaques, one of the pathological hallmarks observed in AD patients. However, recent evidence suggests that the overexpression of APP by itself can confound some of the reported observations. Therefore, we investigated in the present study the App NL-G-F model, an App knock-in (App-KI) mouse model that develops amyloidosis in the absence of APP-overexpression. Our findings at the behavioral, electrophysiological, and histopathological level confirmed an age-dependent increase in Aβ1-42 levels and plaque deposition in these mice in accordance with previous reports. This had apparently no consequences on cognitive performance in a visual discrimination (VD) task, which was largely unaffected in App NL-G-F mice at the ages tested. Additionally, we investigated neurophysiological functioning of several brain areas by phase-amplitude coupling (PAC) analysis, a measure associated with adequate cognitive functioning, during the VD task (starting at 4.5 months) and the exploration of home environment (at 5 and 8 months of age). While we did not detect age-dependent changes in PAC during home environment exploration for both the wild-type and the App NL-G-F mice, we did observe subtle changes in PAC in the wild-type mice that were not present in the App NL-G-F mice.

Several devices exist for treating postprostatectomy incontinence. In specific cases, male slings can offer good results instead of an artificial urinary sphincter. This short consultation guide aims to help in offering the right surgery to the right patient., (Copyright © 2019. Published by Elsevier B.V.)

Background: Robot-assisted surgery is considered to improve ergonomics over standard endoscopic surgery. Nevertheless, previous research demonstrated ergonomic deficits in the current console set-up., Aim: This study was designed to objectively assess body posture in the da Vinci console during robot-assisted endoscopic surgery., Methods: Multiple sagittal photographs from six physicians were taken during robot-assisted procedures. Trunk, neck, shoulder, elbow, hip, and knee angles were calculated and compared to ergonomic preferable joint angles. A 2D geometric model was developed using individual anthropometrics. Optimal seat height, armrest height, and viewer height were calculated. These results were compared to the findings of the sagittal photographs., Results: Mean joint angles show potentially harmful neck angles for all participants. Trunk angles vary between surgeons, from inadequate to correct. In short and very tall individuals, optimal armrest height is outside the adjustment range of the console., Conclusion: The da Vinci Surgical System console seating position results in a nonergonomic neck and trunk angle. The developed geometric model revealed that armrest height has a limited adjustment range. Adjustments to the console and optimization of preoperative settings are goals to further improve ergonomics in robot-assisted surgery., (©2017 van’t Hullenaar C.D.P. et al., published by De Gruyter, Berlin/Boston.)

The Antirrhinum genus has a considerable complexity in the scent profiles produced by different species. We have analyzed the genetic differences between A. majus and A. linkianum , two species divergent in the emission of methyl benzoate, methyl cinnamate, acetophenone, and ocimene. The genetic analysis showed that all compounds segregated in a Mendelian fashion attributable to one or two loci with simple or epistatic interactions. Several lines lacked methyl benzoate, a major Volatile Organic Compound emitted by A. majus but missing in A. linkianum . Using a candidate gene approach, we found that the BENZOIC ACID CARBOXYMETHYL TRANSFERASE from A. linkianum appeared to be a null allele as we could not detect mRNA expression. The coding region did not show significant differences that could explain the loss of expression. The intron-exon boundaries was also conserved indicating that there is no alternative splicing in A. linkianum as compared to A. majus . However, it showed multiple polymorphisms in the 5' promoter region including two insertions, one harboring an IDLE MITE transposon with additional sequences with high homology to the PLENA locus and a second one with somewhat lower homology to the regulatory region of the VENOSA locus . It also had a 778 bp deletion as compared to the A. majus BAMT promoter region. Our results show that the differences in scent emission between A. majus and A. linkianum may be traced back to single genes involved in discrete biosynthetic reactions such as benzoic acid methylation. Thus, natural variation of this complex trait maybe the result of combinations of wild type, and loss of function alleles in different genes involved in discrete VOCs biosynthesis. Furthermore, the presence of active transposable elements in the genus may account for rapid evolution and instability, raising the possibility of adaptation to local pollinators.

Aims: We investigated the accuracy and feasibility of a non-invasive arterial pulse contour technique for continuous measurement of stroke volume (SV) in optimization of atrioventricular (AV) delay in cardiac resynchronization therapy (CRT), by comparing SV changes assessed by Nexfin CO-Trek® (Nexfin) and echo Doppler aortic velocity-time integral (VTIao). Furthermore, we investigated whether AV-delay optimization increases the effect of CRT when compared with a default AV delay (120 ms)., Methods and Results: In 23 CRT patients, biventricular pacing (BiVP) was applied at various AV delays, while recording 10 beats preceding BiVP (baseline) and the first 10 BiVP beats, for both methods in parallel. Agreement between Nexfin and VTIao measurements was evaluated (Bland-Altman) on beat-to-beat changes in SV, as well as on effects of BiVP (averaged over 8 beats) at various AV delays. Individual optimal AV delays, for Nexfin (AVopt-n) and VTIao (AVopt-ao), were derived from the second-order polynomial fitted to the effect measurements of 20 patients. In 252 episodes assessed, the difference between measurements (= Nexfin - VTIao) was -0.6 ± 8.1% for beat-to-beat SV changes and -1.3 ± 7.3% for effects of BiVP. Optimal AV delays for Nexfin were well related to AVopt-ao (R(2) = 0.69). The effect (%) of BiVP at the optimal AV delay was significantly larger than at the default AV delay: median difference (range) being +6.3% (0.1-14.4%; P < 0.001) for VTIao and +4.7% (0.0-14.0%; P < 0.001) for Nexfin., Conclusion: Individual AV optimization increases the effect of CRT. Nexfin is a promising tool in individual CRT optimization, as Nexfin agrees with VTIao on measuring beat-to-beat SV changes and on assessing relative effects of BiVP on SV at various AV delays.

Background: Many manufacturers are producing videolaryngoscopes (VLSs) with differing specifications, user interfaces, and geometry. It is clinically relevant to know the relative performance of the blades. Visualization of the glottis and intubation are often problematic in (extremely) obese patients, and the new video technology may offer better functionality and performance. Although many tracheal intubations with direct laryngoscopy are performed with an unstyletted endotracheal tube, it is recommended to use a stylet for intubation using videolaryngoscopy. In this study, we compared 3 VLSs in morbidly obese patients undergoing intubation for elective surgery and tested whether it is feasible to intubate the tracheas of morbidly obese patients without using a stylet., Methods: One hundred fifty consecutive adult morbidly obese patients (body mass index >35 kg/m(2)) were randomly selected to receive one of 3 VLSs: GlideScope, Storz V-Mac, and McGrath. Direct laryngoscopy scored the best possible view of the glottis; subsequently, the respective VLS was used, and the patient's trachea was intubated. Common preprocedural (e.g., Mallampati grade) and intraprocedural (Cormack-Lehane grade) metrics of intubation difficulty were measured, as well as the dependent variables of intubation time, number of attempts, and subjective difficulty., Results: All 3 VLSs tested offered an equal or better view of the glottis compared with traditional direct laryngoscopy. The number of attempts necessary to intubate the trachea differed significantly among VLSs (average 2.6 +/- 1.0 attempts for the GlideScope, 1.4 +/- 0.7 for the Storz, and 2.9 +/- 0.9 for the McGrath VLS). The average intubation times were 33 +/- 18 s for the GlideScope, 17 +/- 9 s for the Storz, and 41 +/- 25 s for the McGrath VLS., Conclusions: In this study, the VLS with the Macintosh blade (Storz VLS) had a better overall satisfaction score, intubation time, number of intubation attempts, and necessity of extra adjuncts, compared with the 2 other tested devices.

The synthesis and evaluation of benzetimide derivatives showing potent CXCR3 antagonism are described. Optimization of the screening hits led to the identification of more potent CXCR3 antagonists devoid of anti-cholinergic activity and identification of the key pharmacophore moieties of the series.