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Abstract Background This study aimed to assess a potential organ protective effect of volatile sedation in a scenario of severe inflammation with an early cytokine storm (in particular IL-6 elevation) in patients suffering from COVID-19-related lung injury with invasive mechanical ventilation and sedation. Methods This is a small-scale pilot multicenter randomized controlled trial from four tertiary hospitals in Switzerland, conducted between April 2020 and May 2021. 60 patients requiring mechanical ventilation due to severe COVID-19-related lung injury were included and randomized to 48-hour sedation with sevoflurane vs. continuous intravenous sedation (= control) within 24 h after intubation. The primary composite outcome was determined as mortality or persistent organ dysfunction (POD), defined as the need for mechanical ventilation, vasopressors, or renal replacement therapy at day 28. Secondary outcomes were the length of ICU and hospital stay, adverse events, routine laboratory parameters (creatinine, urea), and plasma inflammatory mediators. Results 28 patients were randomized to sevoflurane, 32 to the control arm. The intention-to-treat analysis revealed no difference in the primary endpoint with 11 (39%) sevoflurane and 13 (41%) control patients (p = 0.916) reaching the primary outcome. Five patients died within 28 days in each group (16% vs. 18%, p = 0.817). Of the 28-day survivors, 6 (26%) and 8 (30%) presented with POD (p = 0.781). There was a significant difference regarding the need for vasopressors (1 (4%) patient in the sevoflurane arm, 7 (26%) in the control one (p = 0.028)). Length of ICU stay, hospital stay, and registered adverse events within 28 days were comparable, except for acute kidney injury (AKI), with 11 (39%) sevoflurane vs. 2 (6%) control patients (p = 0.001). The blood levels of IL-6 in the first few days after the onset of the lung injury were less distinctly elevated than expected. Conclusions No evident benefits were observed with short sevoflurane sedation on mortality and POD. Unexpectedly low blood levels of IL-6 might indicate a moderate injury with therefore limited improvement options of sevoflurane. Acute renal issues suggest caution in using sevoflurane for sedation in COVID-19. Trial registration The trial was registered on ClinicalTrials.gov (NCT04355962) on 2020/04/21.

BackgroundFalsified medicines and their international regulation impacts all healthcare sectors and their actors. These regulations aim to strengthen and protect the global pharmaceutical supply chain against falsified medicines. However, an evaluation of the impacts of these regulations on key stakeholders within the legitimate supply chain have not been explored.ObjectiveThis research aimed to evaluate both the positive and negative impacts of falsified medicines regulation on key stakeholders within the global pharmacy sector including including manufacturers, wholesalers, hospital pharmacies, community pharmacy and patients.DesignThis research consists of a systematic review and thematic analysis concerning falsified medicines regulation and the subsequent impacts of existing global regulations on healthcare. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and checklist were utilized for reporting in this systematic review.Data sources and methodsA search of three databases, Embase, ProQuest and PubMed, was undertaken to determine studies applicable to the research question. The Mixed Methods Appraisal Tool (MMAT) was used to assess methodological quality and risk of bias for all included studies.ResultsFrom the initial 657 studies, a final set of 13 relevant studies were identified. The most frequently reported falsified medicines regulation was the Falsified Medicines Directive (FMD) [n = 11]. The impact of falsified medicines regulation in the literature related to four areas: (1) Financial, (2) Social, (3) Organizational, and (4) Pharmacy Practice. These common themes across the included studies frequently relate to challenges and/or concerns associated with falsified medicines regulation implementation as well as both the logistics and practicality of incorporating falsified medicines regulations into daily operations.ConclusionImplementation and enforcement of falsified medicines regulation does not yet appear to categorically fulfill the primary aim of the regulations, to strengthen the drug supply chain. However, in recent years, such regulations have challenged the legitimate pharmaceutical supply change actors as they attempt to successfully implement these regulations. Studies mainly detail the negative impacts of regulation during the implementation phase but with the overall benefit pertaining to the prioritization and enhancement of patient care and safety within the healthcare sector.

Due to the importance of teachers in providing quality education, research in the last two decades has consistently focused on their effectiveness. However, there are inconclusive debates in the literature on the nature of relationships that exist between different supervisory strategies and their links to teachers' job performance. This study used a predictive correlation design to assess how five principals' supervisory practices contribute to teachers' job effectiveness generally and across three specific areas. Secondary school teachers that participated in the study were 284 and were selected using simple and purposive sampling techniques. Data were collected using a questionnaire. A bootstrapping procedure in covariance-based structural equation modelling (CB-SEM) and multiple linear regression analysis were used for hypotheses testing at the .05 alpha level. Among others, findings revealed a significant joint prediction of classroom observation, supervision of sporting activities, instructional aids, team teaching and school record on teachers' job effectiveness generally and in the dimensions of lesson note preparation and classroom management, but not the use of instructional materials. Teachers who reported frequent classroom observation by principals also reported a higher level of lesson preparation but not other aspects of teaching effectiveness. The supervision of sporting activities significantly predicted teachers' overall effectiveness and specific aspects such as lesson preparation, instructional material use, and classroom management. This study can encourage school principals to gain more knowledge, facts and strategies required for effective and efficient school-based supervision.

AbstractDue to the importance of teachers in providing quality education, research in the last two decades has consistently focused on their effectiveness. However, there are inconclusive debates in the literature on the nature of relationships that exist between different supervisory strategies and their links to teachers’ job performance. This study used a predictive correlation design to assess how five principals’ supervisory practices contribute to teachers’ job effectiveness generally and across three specific areas. Secondary school teachers that participated in the study were 284 and were selected using simple and purposive sampling techniques. Data were collected using a questionnaire. A bootstrapping procedure in covariance-based structural equation modelling (CB-SEM) and multiple linear regression analysis were used for hypotheses testing at the .05 alpha level. Among others, findings revealed a significant joint prediction of classroom observation, supervision of sporting activities, instructional aids, team teaching and school record on teachers’ job effectiveness generally and in the dimensions of lesson note preparation and classroom management, but not the use of instructional materials. Teachers who reported frequent classroom observation by principals also reported a higher level of lesson preparation but not other aspects of teaching effectiveness. The supervision of sporting activities significantly predicted teachers’ overall effectiveness and specific aspects such as lesson preparation, instructional material use, and classroom management. This study can encourage school principals to gain more knowledge, facts and strategies required for effective and efficient school-based supervision.

Objective To determine the magnitude of any excess risk of mortality and hospitalisation due to COVID-19 infection in patients with congenital heart disease (CHD) in the UK healthcare system.Methods Matched case–control study within the Clinical Practice Research Datalink study of anonymised general practice records in the National Health Service in England. Patients with CHD were stratified for disease severity according to the European Society of Cardiology guidelines. Presence of a positive COVID-19 test, hospitalisation with a diagnosis of COVID-19 and COVID-19-related mortality were compared in case and control groups.Results 86 441 patients with CHD and 335 839 controls were studied. Of patients with a positive COVID-19 test, patients with CHD were more likely than controls to be hospitalised (22.4% vs 14.5%; OR=1.77 (95% CI 1.60 to 1.96); p=2.11e−28) and suffer COVID-19-related death (6.1% vs 3.8%; OR=1.60 (95% CI 1.35 to 1.89); p=7.00e−08). The excess risk of COVID-19 hospitalisation and death rose with increasing physiological severity of CHD (presence of pulmonary vascular disease and/or cyanosis), rather than anatomical complexity.Conclusions In this study of the COVID-19 pandemic experience, using population health records in over 86000 patients with CHD in England, patients with CHD with COVID-19 were at around 50–75% higher risk of hospitalisation and mortality compared with matched controls with COVID-19. We provide the first primary care-derived estimates for COVID-19 hospitalisation and case-fatality rates in patients with CHD. Some factors predictive of worse COVID-19 outcome in general populations (such as non-white ethnic group), and other CHD-specific comorbidities (such as pulmonary hypertension), influenced outcomes among patients with CHD.

Abstract Adults with congenital heart disease (CHD) face increased risk of various comorbid diseases. Previous work on lung dysfunction in this population has mainly focused on restrictive lung disease, in patients with severe CHD phenotypes. We examined the association of mild CHD with chronic obstructive pulmonary disease (COPD) in the UK Biobank (UKB). Electronic health records (EHR) were used to identify 3385 CHD cases and 479,765 healthy controls in UKB, before performing a case–control analysis over a 20-year study period for a total of > 9.5 M person-years of follow-up. Our analysis showed that UKB participants with CHD are at substantially greater risk of developing COPD than healthy controls (8.7% vs 3.1% prevalence, unadjusted OR 2.98, 95% CI 2.63, 3.36, P = 1.40e−53). Slightly increased rates of smoking were observed amongst CHD cases, however the association with COPD was shown to be robust to adjustment for smoking and other factors known to modulate COPD risk within a multivariable-adjusted Cox regression framework (fully adjusted HR 2.21, 95% CI 1.97, 2.48, P = 5.5e−41). Care for adults with CHD should aim to mitigate their increased risk of COPD, possibly via increased smoking cessation support.

Abstract Directed evolution (DE) is a widely used method for improving the function of biomolecules via multiple rounds of mutation and selection. Microfluidic droplets have emerged as an important means to screen the large libraries needed for DE, but this approach was so far partially limited by the need to lyse cells, recover DNA, and retransform into cells for the next round, necessitating the use of a high‐copy number plasmid or oversampling. The recently developed live cell recovery avoids some of these limitations by directly regrowing selected cells after sorting. However, repeated sorting cycles used to further enrich the most active variants ultimately resulted in unfavourable recovery of empty plasmid vector‐containing cells over those expressing the protein of interest. In this study, we found that engineering of the original expression vector solved the problem of false positives (i.e. plasmids lacking an insert) cells containing empty vectors. Five approaches to measure activity of cell‐displayed enzymes in microdroplets were compared. By comparing various cell treatment methods prior to droplet sorting two things were found. Substrate encapsulation from the start, that is prior to expression of enzyme, showed no disadvantage to post‐induction substrate addition by pico‐injection with respect to recovery of true positive variants. Furthermore in‐droplet cell growth prior to induction of enzyme production improves the total amount of cells retrieved (recovery) and proportion of true positive variants (enrichment) after droplet sorting.

Background: During left-sided heart failure (HF), left atrial and pulmonary venous pressure increase, which may lead to pulmonary congestion. Previous cohort studies, examining participants with symptomatic HF or rheumatic heart disease, suggest a relationship between increased left atrial pressure (LAP) and fractional exhaled nitric oxide (FeNO). Aim: To examine the strength of association between FeNO and echocardiographic assessment of LAP by the E/e’ ratio, to determine if FeNO could be used to identify those with elevated LAP. Design & setting: This cross-sectional cohort study examined a subset of the OxVALVE cohort aged ≥65 years. Data collection was undertaken in primary care practices in central England. Method: Each participant underwent a focused cardiovascular history and clinical examination. Standard transthoracic echocardiographic (TTE) assessment was performed on all participants, with the E/e’ ratio calculated to obtain a validated surrogate of LAP. FeNO was measured in 227 participants. Results: FeNO was higher in males compared with females and no different in participants with asthma, chronic obstructive pulmonary disease (COPD), or those using inhaled steroids. Participants with a high E/e’ (>14) were older, with a higher proportion of females than males. There was no relationship between E/e’ and FeNO, either when measured as a continuous variable or in the group with high E/e’. Conclusion: FeNO was not found to be an accurate predictor of elevated LAP in a primary care setting.

Abstract The genome-wide promoter interactome is primarily maintained and regulated by architectural proteins such as CTCF and cohesin. However, some studies suggest a role for non-coding RNAs (ncRNAs) in this process. We aimed to characterise the regulatory role of RNA-mediated promoter interactions in the control of gene expression. We integrated genome-wide datasets of RNA-chromatin and promoter-genome interactions in human embryonic stem cells (hESCs) to identify putative RNA-mediated promoter interactions. We discovered that CTCF sites were enriched in RNA-PIRs (promoter interacting regions co-localising with RNA-chromatin interaction sites) and genes interacting with RNA-PIRs containing CTCF sites showed higher expression levels. One of the long noncoding RNAs (lncRNAs) expressed in hESCs, Syntaxin 18-Antisense 1 (STX18-AS1), appeared to be involved in an insulating promoter interaction with the neighbouring gene, MSX1. By knocking down STX18-AS1, the MSX1 promoter-PIR interaction was intensified and the target gene (MSX1) expression was down-regulated. Conversely, reduced MSX1 promoter-PIR interactions, resulting from CRISPR-Cas9 deletion of the PIR, increased the expression of MSX1. We conclude that STX18-AS1 RNA antagonised local CTCF-mediated insulating promoter interactions to augment gene expression. Such down-regulation of the insulating promoter interactions by this novel mechanism may explain the higher expression of genes interacting with RNA-PIRs linked to CTCF sites.

This article presents data concerning STX18-AS1, a long noncoding RNA gene identified from a Genome-wide association study of Atrial Septal Defect (ASD). The data describes its expression patterns in human tissues and functions in regulating cardiomyocyte differentiation in vitro. STX18-AS1 is a lncRNA with a higher abundance in developing tissues, including hearts. Its transcription distribution within the embryonic hearts during key heart septation stages supports STX18-AS1’s association with risk SNPs for ASD. The CRISPR stem cell pool in which STX18-AS1 was knocked down, showed reduced CM differentiation efficiency and lower expression of key cardiac transcriptional factors. This indicated its regulative role in supporting the lineage specification from cardiac mesoderm into cardiac progenitors and cardiomyocytes. These data can benefit the understanding of human embryonic heart developmental biology, and the time-course changes of cardiac transcriptional factors during in vitro cardiomyocyte differentiation from human embryonic stem cells.

ObjectiveCardiac surgery and the use of cardiopulmonary bypass initiate a systemic inflammatory response. Wingless-related integration site (WNT) signaling is part of the innate immunity and has been attributed a major role in the regulation of inflammation. In preclinical research, WNT-5a may sustain an inflammatory response and cause endothelial dysfunction. Our aim was to investigate WNT signaling after cardiac surgery and its association with postoperative inflammation (Clinicaltrials.gov, NCT04058496).MethodsIn this prospective, single-center, observational study, 64 consecutive patients for coronary artery bypass grafting (CABG) ± valve surgery were assigned into three groups: off-pump CABG (n = 28), on-pump CABG (n = 16) and combined valve-CABG surgery (n = 20). Blood samples were acquired before surgery, at intensive care unit (ICU) admission and 4, 8, and 48 h thereafter. Plasma concentrations of WNT-5a and its antagonists Secreted frizzled-related protein 1 (sFRP-1), Secreted frizzled-related protein 5 (sFRP-5), and WNT inhibitory factor 1 (WIF-1) were determined by enzyme-linked immunosorbent assay. In addition, plasma concentrations of six inflammatory cytokines were measured by multiplex immunoassay. Parameters were analyzed for evolution of plasma concentration over time, interactions, intergroup differences, and association with clinical outcome parameters.ResultsAt baseline, WNT-5a, sFRP-1, and WIF-1 were present in a minimal concentration, while sFRP-5 was elevated. A higher baseline value of WNT-5a, sFRP-5, and WIF-1 resulted in higher subsequent values of the respective parameter. At ICU admission, WNT-5a and sFRP-5 reached their maximum and minimum value, respectively. WIF-1 decreased over time and was lowest 8 h after surgery. sFRP-1 changed minimally over time. While WNT-5a returned to the baseline within 48 h, sFRP-5 and WIF-1 did not reach their baseline value at 48 h. Of the investigated WNT system components, only WIF-1 partially reflected the severity of surgery. WNT-5a and WIF-1 had an impact on postoperative fluid balance and noradrenaline requirement.ConclusionWNT-5a, sFRP-5, and WIF-1 are part of the systemic inflammatory response after cardiac surgery. WNT-5a peaks immediately after cardiac surgery and returns to baseline within 48 h, presumably modulated by its antagonist sFRP-5. Based on this translational study, WNT-5a antagonism may be further investigated to assess potentially beneficial effects in patients with a dysregulated inflammation after cardiac surgery.

Case series summary In this report we describe the origin of protein loss and development of acute kidney injury after ibuprofen intoxication in two cats. Two 13-month-old neutered male domestic shorthair siblings were presented with acute kidney injury (AKI) and severe glomerular proteinuria following witnessed ibuprofen intoxication 3 days prior. Both cats presented with severe azotaemia (creatinine >900 µmol/l [>10 mg/dl]) and severe proteinuria (urine protein:creatinine [UPC] >20, normal

Background: Infective endocarditis is a heart infection with a first-year mortality rate of ≈ 30%. It has long been thought that infective endocarditis is causally associated with bloodstream seeding with oral bacteria in ≈ 40–45% of cases. This theorem led guideline committees to recommend that individuals at increased risk of infective endocarditis should receive antibiotic prophylaxis before undergoing invasive dental procedures. However, to the best of our knowledge, there has never been a clinical trial to prove the efficacy of antibiotic prophylaxis and there is no good-quality evidence to link invasive dental procedures with infective endocarditis. Many contend that oral bacteria-related infective endocarditis is more likely to result from daily activities (e.g. tooth brushing, flossing and chewing), particularly in those with poor oral hygiene. Objective: The aim of this study was to determine if there is a temporal association between invasive dental procedures and subsequent infective endocarditis, particularly in those at high risk of infective endocarditis. Design: This was a self-controlled, case-crossover design study comparing the number of invasive dental procedures in the 3 months immediately before an infective endocarditis-related hospital admission with that in the preceding 12-month control period. Setting: The study took place in the English NHS. Participants: All individuals admitted to hospital with infective endocarditis between 1 April 2010 and 31 March 2016 were eligible to participate. Interventions: This was an observational study; therefore, there was no intervention. Main outcome measure: The outcome measure was the number of invasive and non-invasive dental procedures in the months before infective endocarditis-related hospital admission. Data sources: NHS Digital provided infective endocarditis-related hospital admissions data and dental procedure data were obtained from the NHS Business Services Authority. Results: The incidence rate of invasive dental procedures decreased in the 3 months before infective endocarditis-related hospital admission (incidence rate ratio 1.34, 95% confidence interval 1.13 to 1.58). Further analysis showed that this was due to loss of dental procedure data in the 2–3 weeks before any infective endocarditis-related hospital admission. Limitations: We found that urgent hospital admissions were a common cause of incomplete courses of dental treatment and, because there is no requirement to record dental procedure data for incomplete courses, this resulted in a significant loss of dental procedure data in the 2–3 weeks before infective endocarditis-related hospital admissions. The data set was also reduced because of the NHS Business Services Authority’s 10-year data destruction policy, reducing the power of the study. The main consequence was a loss of dental procedure data in the critical 3-month case period of the case-crossover analysis (immediately before infective endocarditis-related hospital admission), which did not occur in earlier control periods. Part of the decline in the rate of invasive dental procedures may also be the result of the onset of illness prior to infective endocarditis-related hospital admission, and part may be due to other undefined causes. Conclusions: The loss of dental procedure data in the critical case period immediately before infective endocarditis-related hospital admission makes interpretation of the data difficult and raises uncertainty over any conclusions that can be drawn from this study. Future work: We suggest repeating this study elsewhere using data that are unafflicted by loss of dental procedure data in the critical case period. Trial registration: This trial is registered as ISRCTN11684416. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 28. See the NIHR Journals Library website for further project information.

Aims Rare, deleterious genetic variants in FLT4 are associated with Tetralogy of Fallot (TOF), the most common cyanotic congenital heart disease. The distinct genetic variants in FLT4 are also an established cause of Milroy disease, the most prevalent form of primary hereditary lymphoedema. The phenotypic features of these two conditions are non-overlapping, implying pleiotropic cellular mechanisms during development. Methods and results In this study, we show that FLT4 variants identified in patients with TOF, when expressed in primary human endothelial cells, cause aggregation of FLT4 protein in the perinuclear endoplasmic reticulum, activating proteostatic and metabolic signalling, whereas lymphoedema-associated FLT4 variants and wild-type (WT) FLT4 do not. FLT4 TOF variants display characteristic gene expression profiles in key developmental signalling pathways, revealing a role for FLT4 in cardiogenesis distinct from its role in lymphatic development. Inhibition of proteostatic signalling abrogates these effects, identifying potential avenues for therapeutic intervention. Depletion of flt4 in zebrafish caused cardiac phenotypes of reduced heart size and altered heart looping. These phenotypes were rescued with coinjection of WT human FLT4 mRNA, but incompletely or not at all by mRNA harbouring FLT4 TOF variants. Conclusion Taken together, we identify a pathogenic mechanism for FLT4 variants predisposing to TOF that is distinct from the known dominant negative mechanism of Milroy-causative variants. FLT4 variants give rise to conditions of the two circulatory subdivisions of the vascular system via distinct developmental pleiotropic molecular mechanisms. [ABSTRACT FROM AUTHOR]

Abstract Background Congenital heart disease (CHD) is the commonest birth defect. Studies estimating the prevalence of CHD in school-age children could therefore contribute to quantifying unmet health needs for diagnosis and treatment, particularly in lower-income countries. Data at school age are considerably sparser, and individual studies have generally been of small size. We conducted a literature-based meta-analysis to investigate global trends over a 40-year period. Methods and results Studies reporting on CHD prevalence in school-age children (4–18 years old) from 1970 to 2017 were identified from PubMed, EMBASE, Web of Science and Google Scholar. According to the inclusion criteria, 42 studies including 2,638,475 children, reporting the prevalence of unrepaired CHDs (both pre-school diagnoses and first-time school-age diagnoses), and nine studies including 395,571 children, specifically reporting the prevalence of CHD first diagnosed at school ages, were included. Data were combined using random-effects models. The prevalence of unrepaired CHD in school children during the entire period of study was 3.809 (95% confidence intervals 3.075–4.621)/1000. A lower proportion of male than female school children had unrepaired CHD (OR = 0.84 [95% CI 0.74–0.95]; p = 0.001). Between 1970–1974 and 1995–1999, there was no significant change in the prevalence of unrepaired CHD at school age; subsequently there was an approximately 2.5-fold increase from 1.985 (95% CI 1.074–3.173)/1000 in 1995–1999 to 4.832 (95% CI 3.425–6.480)/1000 in 2010–2014, (p = 0.009). Among all CHD conditions, atrial septal defects and ventricular septal defects chiefly accounted for this increasing trend. The summarised prevalence (1970–2017) of CHD diagnoses first made in childhood was 1.384 (0.955, 1.891)/1000; during this time there was a fall from 2.050 [1.362, 2.877]/1000 pre-1995 to 0.848 [0.626, 1.104]/1000 in 1995–2014 (p = 0.04). Conclusions Globally, these data show an increased prevalence of CHD (mainly mild CHD conditions) recognised at birth/infancy or early childhood, but remaining unrepaired at school-age. In parallel there has been a decrease of first-time CHD diagnoses in school-age children. These together imply a favourable shift of CHD recognition time to earlier in the life course. Despite this, substantial inequalities between higher and lower income countries remain. Increased healthcare resources for people born with CHD, particularly in poorer countries, are required.

The article discusses the use of transcatheter aortic valve implantation (TAVI) as a common procedure for treating aortic stenosis. While TAVI is generally safe, it can be associated with life-threatening complications, such as acute coronary occlusion. Factors that increase the risk of coronary occlusion include small aortic root anatomy, narrow sinuses of Valsalva, bulky leaflet calcification, and a short distance between the transcatheter heart valve and the coronary ostium. The article introduces the ShortCut device, which is a transcatheter leaflet modification device that has shown promising outcomes in preventing coronary occlusion during TAVI procedures. The device allows for simple stabilization, accurate splitting of the valve leaflets, and continuous access to the left ventricle. The study conducted on the device demonstrated its effectiveness, quick procedure time, and safety. While the study has limitations, the ShortCut device shows potential for wider applications in transcatheter valve interventions. [Extracted from the article]

The study of nuclear fission yields has a major impact on the characterization and understanding of the fission process and is mandatory for reactor applications. In the framework of a collaboration between the CEA, the LPSC and the ILL, a program of actinide fission yield measurements has been ongoing for several years at the LOHENGRIN spectrometer. However, the measurement of very low fission yields in the symmetry region and the heavy wing of the distributions is difficult to achieve due to the strong contamination by other masses with much higher yields and requires the development of a new experimental setup. This paper will first present the results of a new absolute measurement of the 235U(nth,f) mass yields using an ionization chamber placed at the exit of the spectrometer. Although very well documented in the literature, these yields show uncertainties lying from 3% to 10% with large discrepancies between libraries and a lack of correlation matrices. New experimental data obtained at the LOHENGRIN spectrometer will be detailed, along with the measurement method and the production of the experimental covariance matrix. The second part will show the development of a Time of Flight (ToF) line in order to improve the background rejection in the mass yield measurements. In the symmetry region, the precision of the measurement is limited by the background estimation due to the charge exchanges with the residual gas of the separator. We plan to analyze the events using a triple coincidence (∆E x E) x ToF, whereas today only (∆E x E) selection is available. The new ToF line is built using Si3N4 foils and secondary electron detectors (SED) for the start and stop detectors. We will present the choices made for the SED technology along with the progress achieved on the ToF line characterization.