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Objective This study aimed to determine the longitudinal change of systemic ventricular function and atrioventricular valve regurgitation after total cavopulmonary connection. Methods In 620 patients who underwent total cavopulmonary connection between 1994 and 2021, 4219 longitudinal echocardiographic examinations of systemic ventricular function and atrioventricular valve regurgitation were evaluated retrospectively. Results The most frequent primary diagnosis was hypoplastic left heart syndrome in 172, followed by single ventricle in 131, tricuspid atresia in 95, and double inlet left ventricle in 91 patients. Dominant right ventricle was observed in 329 (53%) and dominant left ventricle in 291 (47%). Median age at total cavopulmonary connection was 2.3 (1.8–3.4) years. Transplant-free survival at 5, 10, and 15 years after total cavopulmonary connection was 96.3, 94.7, and 93.6%, respectively in patients with dominant right ventricle and 97.3, 94.6, and 94.6%, respectively in those with dominant left ventricle (p = 0.987). Longitudinal analysis of systemic ventricular function was similar in both groups during the first 10 years postoperatively. Thereafter, systemic ventricular function worsened significantly in patients with dominant right ventricle, compared with those with dominant left ventricle (15 years: p = 0.007, 20 years: p = 0.03). Atrioventricular valve regurgitation was more frequent after total cavopulmonary connection in patients with dominant right ventricle compared with those with dominant left ventricle (p Conclusions There was no transplant-free survival difference and no difference in ventricular function between dominant right ventricle and dominant left ventricle for the first 10 years after total cavopulmonary connection. Thereafter, ventricular function in dominant right ventricle was inferior to that in dominant left ventricle. The degree of atrioventricular valve regurgitation was significantly higher in dominant right ventricle, compared with dominant left ventricle, and it was positively associated with ventricular dysfunction, especially in dominant right ventricle.

Objective This study aimed to prove if pulmonary artery size influences survival and if an additional aortopulmonary shunt promotes left pulmonary artery growth after bidirectional cavopulmonary shunt in patients with hypoplastic left heart syndrome. Methods The medical records of patients with hypoplastic left heart syndrome who underwent Norwood procedure and bidirectional cavopulmonary shunt between 2007 and 2020 were reviewed. Right, left, and total (right + left) pulmonary artery indices were calculated according to Nakata and colleagues. Results A total of 158 patients were included in this study. Median age at Norwood and bidirectional cavopulmonary shunt was 8 (7-11) days and 3.6 (3.1-4.6) months, respectively. There were 7 hospital deaths and 12 late deaths. Survival after bidirectional cavopulmonary shunt was 90.3% at 1 year, and 86.2% at 2 years. Total, right, and left pulmonary artery indices were 238 (195-316), 136 (101-185), and 102 (75-130) mm2/m2 at the time of bidirectional cavopulmonary shunt, and they were 237 (198-284), 151 (123-186), and 86 (69-108) mm2/m2 at the time of Fontan. Left pulmonary artery index decreased significantly between the time of bidirectional cavopulmonary shunt and Fontan (p Conclusions Preoperative pulmonary artery index did not affect the mortality after bidirectional cavopulmonary shunt. The partial takedown and additional aortopulmonary shunt for failing bidirectional cavopulmonary shunt were unable to improve left pulmonary artery size.

Objective To determine the outcome of Stanford type B aortic dissection in patients with Marfan syndrome and to evaluate aortic diameters at time of dissection as well as the impact of previous aortic root replacement. Methods Analysis of all patients with Marfan syndrome fulfilling Ghent criteria seen at this institution since 1995 until 2022. Results Thirty-six (19%) out of 188 patients with Marfan syndrome suffered from Stanford type B aortic dissection during the study period. Mean aortic diameter at time of dissection was 39.0 mm (95% CI: 35.6-42.3). Mean pre-dissection diameter (available in 25% of patients) was 32.1 mm (95% CI: 28.0-36.3) and mean expansion was 19% (95% CI: 11.9-26.2). There was no correlation between age and diameter at time of dissection ( Conclusions Stanford type B dissection in patients with Marfan syndrome occurs far below accepted thresholds for intervention. Risk for type B dissection is present throughout lifetime and two third of patients need an intervention after dissection. There is no difference in freedom from type B dissection between a Bentall procedure and a valve-sparing root replacement.

OBJECTIVES Studies focused on infants with univentricular heart undergoing stage I palliation other than the Norwood procedure remain a topic of great interest. This study evaluated the outcome of infants who underwent systemic to pulmonary shunt (SPS) or pulmonary artery banding (PAB). METHODS Infants who underwent SPS or PAB as stage I palliation between 1994 and 2019 were included. Survival and late systemic ventricular function were evaluated. RESULTS Out of 242 patients, 188 underwent SPS (77.7%) and 54 PAB (22.3%). Main diagnosis included tricuspid atresia, unbalanced atrioventricular septal defects, double inlet left ventricles and single ventricles with other morphology. Thirty-eight patients died before stage II palliation (15.7%). Stage II palliation was performed in 182 patients (75.2%), and mortality between stages II and III was 11 (5.6%). Stage III palliation was performed in 160 (66.1%) patients. Survival at 1, 5 and 15 years after stage I procedure was 81.9, 77.1 and 76.2%, respectively, and similar between both procedures (P = 0.97). Premature birth [P = 0.03, hazard ratio (HR) = 2.1], heterotaxy (P = 0.006, HR = 2.4) and dominant right ventricle (P = 0.015, HR = 2.2) were factors associated to mortality. Unbalanced atrioventricular septal defect (P = 0.005, HR = 4.6) was a factor associated to systemic ventricular dysfunction. CONCLUSIONS In patients with univentricular heart who underwent SPS and PAB as stage I palliation, survival at 15 years was 76%, regardless of th chosen approach. Premature birth, heterotaxy and dominant right ventricle were associated to mortality.

OBJECTIVES The aim of this study was to explore sex and gender differences regarding aortic events in Marfan patients. METHODS We analysed all data from our connective tissue disorder database. Only patients with Marfan syndrome were included. For analysis, patients were divided by sex. Female patients were further divided into 2 subgroups: with versus without children. Aortic events were defined as Stanford type A aortic dissection (TAAD) or type B aortic dissection (TBAD) or any aortic intervention. RESULTS A population of 183 Marfan patients was analysed for the purpose of this study. One hundred four (57%) were male and 79 (43%) were female patients. Thirty-seven (47%) of the 79 female patients had at least 1 child. Male patients had a significantly higher probability of experiencing an aortic event (P = 0.015) compared to female patients. However, there was no increased probability for recurrent events in male patients compared to female patients (P = 0.063). Follow-up revealed no sex and gender differences in the occurrence of Stanford TAAD or TBAD between male and female patients (P = 0.324/P = 0.534). While 11% of women with children suffered from peripartum aortic events, 24% experienced Stanford TAAD unrelated to pregnancy. CONCLUSIONS Male patients have a higher risk of aortic events than female patients. The majority of women were not aware of their Marfan syndrome diagnosis before conceiving. One out of 10 women suffered from peripartum Stanford TAAD or TBAD. Twice as many female patients with children suffered from aortic dissection unrelated to childbirth. There were no sex and gender differences affecting mortality in Marfan patients.

Endothelial progenitor cells (EPC) may influence the integrity and stability of the vascular endothelium. The association of an altered total EPC number and function with cardiovascular diseases (CVD) and risk factors (CVF) was discussed; however, their role and applicability as biomarkers for clinical purposes have not yet been defined. Endothelial dysfunction is one of the key mechanisms in CVD. The assessment of endothelial dysfunction in vivo remains a major challenge, especially for a clinical evaluation of the need for therapeutic interventions or for primary prevention of CVD. One of the main challenges is the heterogeneity of this particular cell population. Endothelial cells (EC) can become senescent, and the majority of circulating endothelial cells (CEC) show evidence of apoptosis or necrosis. There are a few viable CECs that have properties similar to those of an endothelial progenitor cell. To use EPC levels as a biomarker for vascular function and cumulative cardiovascular risk, a correct definition of their phenotype, as well as an update on the clinical application and practicability of current isolation methods, are an urgent priority.

This study aims to clarify the relation of development of aortopulmonary collateral arteries (APCs) with anatomical sub-types and the shunt types at Norwood procedure in patients with hypoplastic left heart syndrome (HLHS). A total of 140 patients with HLHS who completed 3 staged palliation between 2003 and 2019 were included. Incidence of APCs and corresponding interventions were examined using angiogram by cardiac catheterization, with respect to the anatomical sub-types and shunt types. Totally, APCs were observed in 87 (62%) of the patients; pre-stage II in 32 (23%), pre-stage III in 64 (46%), and after stage III in 40 (29%). The incidence of APCs before stage II was significantly higher in patients with aortic atresia/mitral atresia (AA/MA) compared with other sub-types (P = 0.022). Patients with right ventricle to pulmonary artery conduit (RVPAC) had a higher incidence of APCs originating from the descending aorta, compared with those with modified Blalock-Taussig shunt (20% vs 2%, P= 0.002). Interventions for APCs were performed in 58 (41%) patients; before stage II in 10 (7%), after stage II in 7 (5%), before stage III in 22 (16%), and after stage III in 32 (23%). Patients with AA/MA had more interventions before stage II (P= 0.019), and patients with aortic stenosis/mitral stenosis (AS/MS) had a lower incidence of interventions after stage III (P= 0.047). More than half of the patients with HLHS developed APCs. Before stage II, patients with AA/MA sub-type had a higher incidence of APCs, and those with RVPAC had significantly more APCs from the descending aorta.

BACKGROUND Extracorporeal cardiopulmonary resuscitation (ECPR) is increasingly used in patients with out-of-hospital or in-hospital cardiac arrest in whom conventional cardiopulmonary resuscitation remains unsuccessful. The aim of this study was to analyze the impact of initial cardiac rhythm - detected on-site of the cardiac arrest - on mortality. METHODS We performed a retrospective cohort study of patients who received ECPR in our tertiary care cardiac arrest center. Patients were divided into three groups depending on their cardiac rhythm: shockable rhythm, pulseless electrical activity, and asystole. The primary endpoint was mortality within the first 7���days after ECPR deployment. Secondary endpoints were mortality within 28���days and impact of pre-ECPR potassium, serum lactate, pH and pCO2 on mortality. The association of the initial cardiac rhythm and the location of arrhythmia detection (patient monitored in hospital [category: monitored], not monitored but hospitalized [in-hospital], not monitored, not hospitalized [out-of hospital]) with the primary and secondary outcome was examined by means of univariable and multivariable logistic regression. RESULTS Sixty-five patients could be included in the final analysis. Thirty-two patients (49.2%, 95%CI 36.6% - 61.9%) died within the first 7���days. In terms of 7-day-mortality patients differed in the initial cardiac rhythm (p=0.040) and with respect of the location of arrhythmia detection (p=0.002). Shockable cardiac rhythm (crude OR 0.21; 95%CI 0.03 - 0.98) and pulseless electrical activity (0.13; 0.02 - 0.61) as the initial rhythm on-site showed better odds for survival compared to asystole. However, this association did neither persist in adjusted analysis nor in pairwise comparison. DISCUSSION The study could not demonstrate a better outcome with shockable rhythm after ECPR. More homogeneous and adequately powered cohorts are needed to better understand the impact of cardiac rhythm on patient outcome after ECPR.

Rho5, the yeast homolog of human Rac1, is a small GTPase which regulates the cell response to nutrient and oxidative stress by inducing mitophagy and apoptosis. It is activated by a dimeric GEF composed of the subunits Dck1 and Lmo1. Upon stress, all three proteins rapidly translocate from the cell surface (Rho5) and a diffuse cytosolic distribution (Dck1 and Lmo1) to mitochondria, with translocation of the GTPase depending on both GEF subunits. We here show that the latter associate with mitochondria independent from each other and from Rho5. The trapping of Dck1-GFP or GFP-Lmo1 to the mitochondrial surface by a specific nanobody fused to the transmembrane domain (TMD) of Fis1 results in a loss of function, mimicking the phenotypes of the respective gene deletions, dck1 or lmo1. Direct fusion of Rho5 to Fis1TMD, i.e., permanent attachment to the mitochondria, also mimics the phenotypes of an rho5 deletion. Together, these data suggest that the GTPase needs to be activated at the plasma membrane prior to its translocation in order to fulfill its function in the oxidative stress response. This notion is substantiated by the observation that strains carrying fusions of Rho5 to the cell wall integrity sensor Mid2, confining the GTPase to the plasma membrane, retained their function. We propose a model in which Rho5 activated at the plasma membrane represses the oxidative stress response under standard growth conditions. This repression is relieved upon its GEF-mediated translocation to mitochondria, thus triggering mitophagy and apoptosis.

OBJECTIVES This study was performed to determine the clinical and haemodynamic variables associated with early adverse outcomes after the neonatal Norwood procedure. METHODS Patients who underwent the neonatal Norwood procedure between 2001 and 2019 were included. The patient diagnosis, morphological characteristics and haemodynamic parameters were analysed to identify factors associated with length of stay (LOS) in the intensive care unit (ICU) and mortality during the stay. RESULTS A total of 322 patients were depicted. The median age and weight at the Norwood procedure were 9 days and 3.2 kg, respectively. Certain morphological and preoperative parameters, such as birth weight below 2.5 kg, restrictive atrial septal defect, extracardiac anomalies and the diameter of the ascending aorta, were found to be associated with the LOS in the ICU. Analysis using early postoperative haemodynamic variables revealed that systolic arterial pressure, diastolic arterial pressure, serum lactate levels and reduced ventricular function at 2 days postoperatively were associated with the LOS in the ICU. Birth weight CONCLUSIONS The LOS in the ICU after the Norwood procedure was predicted by early postoperative haemodynamic variables, suggesting that good early postoperative haemodynamics determine early recovery. A prolonged stay in the ICU after the Norwood procedure was associated with late mortality.

OBJECTIVES The goal of this study was to report the long-term outcomes of patients with Marfan syndrome who had aortic surgery on any aortic segment except for the replacement of the aortic root itself. METHODS An observational retrospective single-centre study was conducted with 115 Marfan syndrome patients who underwent 189 major aortic interventions from 1995 until 2018. Patients without aortic root replacement were identified and aortic root growth was analysed over time. RESULTS Eleven of 115 patients (9.5%) did not have aortic root replacement during a follow-up of 10.5 [standard deviation (SD) 5.7] years and a mean age at last follow-up of 53.9 (SD 13.4) years. Patients without root replacement did not suffer less frequently from any type of acute aortic dissection (type A 27% vs 25%, P = 0.999; type B 36% vs 25%, P = 0.474). Patients with native aortic roots did not undergo fewer aortic interventions than those with aortic root replacement [12/11, mean 1.09 (SD 0.54) operations/patient vs 177/104, mean 1.7 (SD 1.3); P = 0.128]. Progression of the aortic root dimension was 0.5 (SD 0.3) mm/year in the group of patients with native aortic roots. CONCLUSIONS Current data suggest that 10% of patients with Marfan syndrome with previous aortic surgery will be free from aortic root replacement until the sixth decade of life.

The milk yeast Kluyveromyces lactis degrades glucose through glycolysis and the pentose phosphate pathway and follows a mainly respiratory metabolism. Here, we investigated the role of two reactions which are required for the final steps of glucose degradation from both pathways, as well as for gluconeogenesis, namely fructose-1,6-bisphosphate aldolase (FBA) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH). In silico analyses identified one gene encoding the former (KlFBA1), and three genes encoding isoforms of the latter (KlTDH1, KlTDH2, KlGDP1). Phenotypic analyses were performed by deleting the genes from the haploid K. lactis genome. While Klfba1 deletions lacked detectable FBA activity, they still grew poorly on glucose. To investigate the in vivo importance of the GAPDH isoforms, different mutant combinations were analyzed for their growth behavior and enzymatic activity. KlTdh2 represented the major glycolytic GAPDH isoform, as its lack caused a slower growth on glucose. Cells lacking both KlTdh1 and KlTdh2 failed to grow on glucose but were still able to use ethanol as sole carbon sources, indicating that KlGdp1 is sufficient to promote gluconeogenesis. Life-cell fluorescence microscopy revealed that KlTdh2 accumulated in the nucleus upon exposure to oxidative stress, suggesting a moonlighting function of this isoform in the regulation of gene expression. Heterologous complementation of the Klfba1 deletion by the human ALDOA gene renders K. lactis a promising host for heterologous expression of human disease alleles and/or a screening system for specific drugs.

Hanseniaspora uvarum is an ascomycetous yeast that frequently dominates the population in the first two days of wine fermentations. It contributes to the production of many beneficial as well as detrimental aroma compounds. While the genome sequence of the diploid type strain DSM 2768 has been largely elucidated, transformation by electroporation was only recently achieved. We here provide an elaborate toolset for the genetic manipulation of this yeast. A chromosomal replication origin was isolated and used for the construction of episomal, self-replicating cloning vectors. Moreover, homozygous auxotrophic deletion markers (Huura3, Huhis3, Huleu2, Huade2) have been obtained in the diploid genome as future recipients and a proof of principle for the application of PCR-based one-step gene deletion strategies. Besides a hygromycin resistance cassette, a kanamycin resistance gene was established as a dominant marker for selection on G418. Recyclable deletion cassettes flanked by loxP-sites and the corresponding Cre-recombinase expression vectors were tailored. Moreover, we report on a chemical transformation procedure with the use of freeze-competent cells. Together, these techniques and constructs pave the way for efficient and targeted manipulations of H. uvarum.

In on-line comprehensive two-dimensional liquid chromatography (LC × LC), the combination of similar chromatographic modes such as reversed-phase liquid chromatography × reversed-phase liquid chromatography (RPLC × RPLC) usually leads to the partial occupation of the available separation space. A possible solution to circumvent this issue may be to dynamically adjust the gradient elution in the second dimension (

OBJECTIVES We sought to identify the prevalence of surgical reintervention on the neo-aorta after Norwood procedure and its impact on long-term outcomes. METHODS We reviewed the medical records of all patients who underwent Norwood procedure. The impacts of surgical neoaortic reintervention on outcomes were analysed in each stage of palliation. RESULTS A total of 335 patients were included in this study. Thirty patients underwent surgical reintervention on the neo-aorta after Norwood procedure. The timing of initial reintervention was before stage II in 13 patients, at stage II in 7, between stage II and stage III in 5, at stage III in 3 and after stage III in 2. A reintervention before stage II was significantly associated with mortality (HR 14.4, 95% confidence interval 6.00–34.6, P < 0.001). In patients who underwent stage II (n = 251), reintervention had no significant impact on mortality. In patients who underwent stage III (n = 188), the previous reintervention was significantly associated with higher mean pulmonary pressure (P = 0.05) and a higher rate of reduced ventricular function (P = 0.002). Greater than mild atrioventricular valve regurgitation was significantly associated with the development of a neoaortic arch stenosis after stage II (P = 0.03). CONCLUSIONS Surgical reinterventions on the neo-aorta were required in each inter-stage phase. A surgical neoaortic reintervention was not related to increased mortality after stage II but significantly associated with a higher rate of reduced ventricular function and elevated mean pulmonary artery pressure.

International audience; Differences in elution strength between the sample solvent and the mobile phase usually give rise to undesirable effects on the chromatographic separation, which may range from slight broadening to severe peak deformation or even splitting. In the most extreme case, the retention factor of the analyte at the head of the column is so small at the time of injection that part of the analyte goes through the column with very little interaction with the stationary phase and hence elutes very close to the column dead time. This phenomenon is known as breakthrough. Usually, during breakthrough, the retained peak displays a wide array of deformations and it is not rare that multiple retained peaks appear for a given injected analyte. However, under certain conditions, it has been demonstrated that these deleterious effects could fully disappear, leaving only one breakthrough peak and one symmetrical peak on the chromatogram. This so-called “total breakthrough” phenomenon was recently highlighted in the specific context of the 2D-LC separation of peptides but has yet to be explained. In the present paper, we describe the results of a comprehensive study aiming to better understand and define the conditions of emergence of both breakthrough and total breakthrough phenomena in liquid chromatography. The effects of a broad range of parameters, including the nature of the solute, the retention mechanism, the injection and elution conditions, the column temperature, and the injected sample concentration on the occurrence of both phenomena were investigated. While breakthrough was found to occur for all studied compounds, it appears that the presence of positive charges on the molecule is a prerequisite for observing a total breakthrough phenomenon. Among all the parameters investigated in this work, only the injection conditions and the analyte retention were found to be impactful on the onset of both phenomena. This finding allowed us to suggest one necessary and sufficient condition, relying on the injection of critical volumes to observe each respective phenomenon. These critical volumes only depend on the column dead volume and the retention factor of the analyte in the injection solvent.

We report on a numerical investigation of the different steps in the development of the spatial concentration profiles developing along the axis of a liquid chromatography column when injecting large relative volumes (>10 to 20% of column volume) of analytes dissolved in a high solvent strength solvent band as can be encountered in the second dimension (2D) column of a two-dimensional liquid chromatography (2D-LC) system. More specifically, we made a detailed study of the different retention and the axial band broadening effects leading to the double-headed peak shapes or strongly fronting peaks that can be experimentally observed under certain conditions in 2D-LC. The establishment of these intricate peak profiles is discussed in all its fine, mechanistic details. The effect of the volume of the column, the volume and the shape of the sample band, the retention properties of the analyte and the band broadening experienced by the analytes and the sample solvent are investigated. A good agreement between the simulations and the experimental observations with caffeine and methylparaben injected in acetonitrile/water (ACN/H2O) mobile phase with different injection volumes is obtained. Save the difference in dwell volume, key features of experimental and simulated chromatograms agree within a few %. The simulations are also validated against a number of simple mathematical rules of thumb that can be established to predict the occurrence of a breakthrough fraction and estimate the amount of breakthrough.

In two-dimensional liquid chromatography, the combination of hydrophilic interaction liquid chromatography (HILIC) and reversed-phase liquid chromatography (RPLC) is very attractive due to the complementarity of their separation mechanisms. On-line comprehensive HILIC x RPLC is well-known to give rise to a large retention space coverage when dealing with ionisable compounds. However, method development in on-line HILIC x RPLC is challenging due to the reversed solvent strength between both dimensions, which can greatly affect the peak shapes in the second RPLC dimension, and thus the separation quality and the method sensitivity. In the present contribution, we compared four strategies designed to avoid this problem: (1) flow splitting, which consists in reducing the injection volume in the second dimension (2D), (2) on-line dilution with a make-up flow and (3) on-line dilution with Active Solvent Modulation (ASM), which both consist in reducing the solvent strength of the injected fractions, and (4) Total Breakthrough Strategy, which we recently proposed. Unlike the three preceding strategies, this latter one consists in injecting large volumes of strong solvent in 2D. The performance of each strategy was evaluated for sub-hour separations of a tryptic digest in on-line HILIC x RPLC. In this work, we considered the critical case for which the same column internal diameters (i.e. 2.1 mm here) are used in both dimensions. Peak capacity, peak shapes and peak intensities were considered for this evaluation. The highest peak capacity could be achieved with Total Breakthrough Strategy while the lowest one with on-line dilution using ASM. Peak intensities were usually higher with on-line dilution approaches (make-up flow and ASM). However, despite the presence of breakthrough, peak intensities were approximately 7-fold higher with Total Breakthrough Strategy than with flow splitting.

Altered lipid metabolism has been shown to be of major importance in a range of metabolic diseases, with particular importance in cardiovascular disease (CVD). As a key metabolic product, altered lipoprotein(a) (Lp(a)) levels may be associated with adverse clinical outcomes in high-risk cardiovascular patients undergoing cardiac surgery. We aimed to investigate the impact of the important metabolite Lp(a) on complications and clinical outcomes in high-risk patients. A prospective observational cohort study was performed. Data were derived from the Bern Perioperative Biobank (ClinicalTrials.gov NCT04767685), and included 192 adult patients undergoing elective cardiac surgery. Blood samples were collected at 24 h preoperatively, before induction of general anaesthesia, upon weaning from cardiopulmonary bypass (CPB), and the first morning after surgery. Clinical endpoints included stroke, myocardial infarction, and mortality within 30 days after surgery or within 1 year. Patients were grouped according to their preoperative Lp(a) levels: &lt, 30 mg/dL (n = 121, 63%) or &gt, 30 mg/dL (n = 71, 37%). The groups with increased vs. normal Lp(a) levels were comparable with regard to preoperative demographics and comorbidities. Median age was 67 years (interquartile range (IQR) 60.0, 73.0), with median body mass index (BMI) of 23.1 kg/m2 (23.7, 30.4), and the majority of patients being males (75.5%). Over the observational interval, Lp(a) levels decreased in all types of cardiac surgery after CPB (mean decline of approximately −5 mg/dL). While Lp(a) levels decreased in all patients following CPB, this observation was considerably pronounced in patients undergoing deep hypothermic circulatory arrest (DHCA) (decrease to preoperative Lp(a) levels by −35% (95% CI −68, −1.7), p = 0.039). Increased Lp(a) levels were neither associated with increased rates of perioperative stroke or major adverse events in patients undergoing cardiac surgery, nor with overall mortality in the perioperative period, or at one year after surgery. Other than for cohorts in neurology and cardiology, elevated Lp(a) might not be a risk factor for perioperative events in cardiac surgery.

In the present work, we have investigated the combination of hydrophilic interaction liquid chromatography (HILIC) and reversed phase liquid chromatography (RPLC) for the separation of peptides in on-line HILIC x RPLC. This combination usually leads to significant solvent strength mismatch, since a weak solvent in HILIC becomes a strong solvent in RPLC. This may result in band broadening, peak distortion, and breakthrough phenomena. Our focus was directed towards the reduction of band broadening and peak distortion. The conditions of the emergence of breakthrough could be investigated with high resolution mass spectrometry (HRMS) detection. The importance of both the injection volume and the difference in composition between injection and elution solvents was highlighted. Reported strategies to avoid bad peak shapes mostly rely either on flow splitting to limit the injection volume, or on on-line dilution. Here, we propose an alternative approach which consists in injecting large volumes in the second dimension. In this case, no flow-splitting nor dilution prior to the second dimension is required. Our results show that above a certain critical injected volume, depending on both the compound and the elution conditions, narrow and symmetrical peaks can be obtained, despite the persistence of breakthrough. As a result, the injected volume in the second dimension must be larger than the largest critical volume. This counter-intuitive approach was applied for the on-line HILIC x RPLC-UV-HRMS analysis of a complex tryptic digest sample. A peak capacity close to 1500 could be achieved in 30 min, which is two-fold higher than in RPLC x RPLC within the same analysis time.

AIMS OF THE STUDY: Minimally invasive extracorporeal circulation (MiECC) is an established alternative to conventional extracorporeal circulation (CECC) in coronary artery bypass graft surgery (CABG), but data on its use in cardiac reoperations are limited. We aimed to analyse perioperative morbidity and mortality in adult patients undergoing reoperations for isolated CABG using either CECC or MiECC circuits at our centre. METHODS AND RESULTS: In a single centre retrospective observational study of all adult patients undergoing cardiac reoperations for isolated CABG between 2004 and 2016, we identified 310 patients, and excluded those who received concomitant cardiac procedures (n = 205). Of the remaining 105 patients, 47 received isolated redo-CABG using MiECC, and 58 received CECC. Propensity score modelling was performed, and inversed probability treatment analysis was used between the treatment groups. Primary endpoint was 30-day all-cause mortality. Secondary endpoints included major adverse cardiac or cerebrovascular events or need for conversion to CECC. Groups were comparable, apart from a higher incidence of NYHA class III or higher in CECC group (33.5% vs 8.6%, p= 0.004). Shorter times for operation, cardiopulmonary bypass and aortic cross-clamp were observed in the MiECC group. The incidence of postoperative atrial fibrillation was significantly lower with MiECC (22.1%, p = 0.012). No significant difference was observed in all-cause 30-day mortality between the MiECC and CECC groups (6.8% vs. 8.3%, p = 0.81). CONCLUSION: We found no difference in overall mortality between CECC and MiECC in patients undergoing reoperation for isolated CABG. Furthermore, we found no indication of differences in most outcomes between extracorporeal circuit types. In the case of redo-CABG, MiECC could provide an alternative strategy.

International audience; The characterization of complex mixtures is a challenging issue for the development of innovative processes dedicated to biofuels and bio-products production. The huge number of compounds present in biomass fast pyrolysis oils combined with the large diversity of chemical functions represent a bottleneck as regards analytical technique development. For the extensive characterization of complex samples, supercritical fluid chromatography (SFC) can be alternative to usual separation techniques such as gas (GC) or liquid chromatography (LC). In this study, an approach is proposed to define the best conditions for the SFC separation of a fast pyrolysis bio-oil. This approach was based on SFC data obtained directly from the bio-oil itself instead of selecting model compounds as usually done. SFC conditions were optimized by using three specific, easy-to-use and quantitative criteria aiming at maximizing the separation power. Polar stationary phases (ethylpyridine bonded silica) associated to a mix of acetonitrile and water as polarity modifier provided the best results, with more than 120 peaks detected in SFC-UV.

Background Simultaneous transapical implantation of transcatheter heart valves in the native mitral and aortic position may be considered as an alternative to surgical valve replacement in high-risk patients presenting with combined valve disease. Case presentation A 59-year-old female with severe aortic stenosis, severe mitral stenosis with mild mitral insufficiency, persistent atrial fibrillation, severe chronic obstructive pulmonary disease and NYHA class of IV was evaluated by our interdisciplinary heart team. Due to the calculated Euroscore II, logistic Euroscore with 10% and 17% a decision was made towards a transapical TAVI approach. The implantation of a Sapien 3 (Edwards Lifesciences) valve in the aortic position was performed and the perioperative TEE showed a good result. The preoperative imaging revealed a narrow LVOT with risk for post interventional left ventricular outflow tract obstruction. Accordingly, it was decided against the use of balloon-expanding valves for the mitral valve position in the interdisciplinary team, as it is not repositionable. Instead, it was decided for the use of a Lotus (Boston Scientific) valve, as it is repositionable and therefore possible to retract in case of LVOT obstruction. In the present case of double valve intervention, the implantation attempt of a fully repositionable transcatheter heart valve into the native mitral annulus resulted in acute LVOT obstruction requiring immediate removal of the device. The patient was extubated and experienced uneventful postoperative recovery. Conclusions The case shows that improved preoperative work-up is necessary for better prediction of significant LVOT obstruction following transcatheter mitral valve implantation. In borderline cases, the use of a fully repositionable device is preferred.

Proceedings of the Design Society / International Conference on Engineering Design 39(1), 1077-1086 (2020). doi:10.1017/dsd.2020.20, Published by Cambridge University Press, Cambridge

Avian schistosomes are of medical and veterinary importance as they are responsible for the annually occurring cercarial dermatitis outbreaks. For Austria, so far, only Trichobilharzia szidati Neuhaus 1952 was confirmed on species level as causative agent of cercarial dermatitis. Here we present the first record of Trichobilharzia franki Müller & Kimmig 1994 in Austria. The species was detected during a survey of digenean trematodes in Upper Austrian water bodies. Furthermore, we provide DNA barcodes of T. franki as well as measurements of several parasite individuals to indicate the intraspecific diversity. We also recommend the usage of an alternative primer pair, since the “standard COI primer pair” previously used for Schistosomatidae amplified an aberrant fragment in the sequence of T. franki. Overall, our study shows how limited our knowledge about occurrence and distribution of avian schistosomes in Austria is and how important it is to acquire such a knowledge to estimate ecological and epidemiological risks in the future.

16th International Conference on Engineering Design, DESIGN 2020, online, 26 Oct 2020 - 29 Oct 2020; Proceedings of the Design Society / DESIGN conference 1, 697-706 (2020). doi:10.1017/dsd.2020.98 special issue: "Proceedings of the Design Society: DESIGN Conference, Volume 1 - May 2020", Published by Cambridge University Press, Cambridge

International audience; The petroleum industry is increasingly concerned with the conversion of vacuum residues as a consequence of decreased conventional crude oil availability. The compositional analysis of heavy oil products has become a key step in conversion processes, but the complexity of these oil matrices tends to increase with their boiling point. In this study, comprehensive two-dimensional liquid chromatography (LCxLC) coupled to inductively coupled mass spectrometry (ICP-MS/MS) is considered with a view to meet new requirements and to bring additional information regarding the species present in these matrices. In search for a high degree of orthogonality, two separation techniques involving two different retention mechanisms were evaluated: Size Exclusion Chromatography (SEC) and Reverse Phase Liquid Chromatography (RPLC). In SEC, the analytes are separated according to their molecular weight while according to their hydrophobicity in RPLC. The separation power of both individual separation techniques was first evaluated. Off-line and on-line LCxLC were compared on the basis of an optimization approach. It is shown that off-line SECxRPLC can provide, for the same analysis time of 150 min, a higher peak capacity (2600 vs 1700) than on-line RPLCxSEC while a similar dilution factor (close to 30) but also requires far fewer fractions to be analyzed (12 vs 400). Asphaltenes which constitute the heaviest fraction of crude oils (obtained from petroleum industry) were analyzed by the developed off-line SECxRPLC method. The resulting 2D-contour plots show that co-elutions could be removed leading, for the first time, to new information on high molecular weight species containing sulfur and vanadium.

AIM OF STUDY To report our experience of late correction after infancy in patients with tetralogy of Fallot (ToF). METHODS Observational single-centre retrospective analysis of the surgical techniques and perioperative development of patients from developing countries undergoing total surgical correction of ToF after infancy, between 1 November 2011 and 30 November 2016. Variables are presented as numbers with percentages or as mean ± standard deviation. Due to the setting of the humanitarian programme, clinical and echocardiographic follow-up procedures could be conducted for only one month postoperatively. RESULTS Twenty-five children (mean age: 70.8 ± 42 months, range 23-163; 44% female) underwent total surgical correction of ToF. Two patients (0.8%) initially received a Blalock-Taussig shunt and underwent subsequent correction 24 and 108 months later, respectively. Preoperative mean right ventricular/pulmonary artery (RV/PA) gradient was 84 ± 32 mm Hg, with a Nakata index of 164 ± 71 mm2/m2. Major aortopulmonary collateral arteries (MAPCAs) were observed in eight children (32%), six (26%) of whom underwent transcatheter closure before surgery. 24 children (96%) underwent a valve-sparing pulmonary valve repair and one patient received a transannular patch (TAP). There were no cases which saw major adverse cardiac and cerebrovascular events (MACCE). Mean duration of mechanical ventilation was 28 ± 19.6 hours (range 7-76). Pre-discharge echocardiography demonstrated a mean RV/PA gradient of 25 ± 5.7 mm Hg, with left ventricular ejection fraction >60% in all cases. Overall length of hospital stay was 11.7 ± 4.5 days. There were no in-hospital mortality cases. CONCLUSIONS Late surgical correction of ToF can be safely performed and produce highly satisfying early postoperative results comparable to those of classical “timely” correction. A valve-sparing technique can be applied in the majority of children.

Objective Type A aortic dissection is a life-threatening disease requiring immediate surgical treatment. With emerging catheter-based technologies, endovascular stent-graft implantation to treat aneurysms and dissections has become a standardized procedure. However, endovascular treatment of the ascending aorta remains challenging. Thus we designed an ascending aortic dissection model to allow simulation of endovascular treatment. Methods Five formalin-fixed human aortas were prepared. The ascending aorta was opened semicircularly in the middle portion and the medial layer was separated from the intima. The intimal tube was readapted using running monofilament sutures. The preparations were assessed by 128-slice computed tomography. A bare-metal stent was implanted for thoracic endovascular aortic repair in 4 of the aortic dissection models. Results Separation of the intimal and medial layer of the aorta was considered to be sufficient because computed tomography showed a clear image of the dissection membrane in each aorta. The dissection was located 3.9 ± 1.4 cm proximally from the aortic annulus, with a length of 4.6 ± 0.9 cm. Before stent implantation, the mean distance from the intimal flap to the aortic wall was measured as 0.63 ± 0.163 cm in the ascending aorta. After stent implantation, this distance decreased to 0.26 ± 0.12 cm. Conclusion This model of aortic dissection of the ascending human aorta was reproducible with a comparable pathological and morphological appearance. The technique and model can be used to evaluate new stent-graft technologies to treat type A dissection and facilitate training for surgeons.

Objective Porcine small intestinal submucosa extracellular matrix is a biological substitute used in cardiovascular surgery to correct congenital heart defects. Previous studies with this material have shown satisfactory results. In contrast, there are singular reports of patch-associated complications with CorMatrix small intestinal submucosa extracellular matrix. We report the histopathological findings of explanted extracellular matrix patches that were removed because of early failure in patients with congenital heart defects. Methods Explanted patch materials from 4 patients (aged 9 months to 41 years), who underwent reoperation due to early patch failure, were analyzed. Initial surgery comprised one aortic valve reconstruction, one pulmonary valve reconstruction, one atrioventricular septal defect repair, and one aortic arch enlargement. The interval between operations ranged from 69 to 553 days. Results Residual extracellular matrix patch material was evident at explantation in all cases and presented as a structured eosinophilic and anucleate specimen. In two cases, a local focus of scarring and pseudocartilaginous transformation with evidence of calcification was found. There was no evidence of absorption of patch material in any case, nor repopulation by organized tissue formation. Conclusions Histologic examination of explanted extracellular matrix patches showed no evidence of resorption or relevant repopulation with resident cells nor formation of functional tissue structures. In contrast, a mixed chronic inflammatory infiltration, early signs of calcification, and scarring as well as focal pseudocartilaginous transformation were found. Considering recent reports, close follow-up of patients with extracellular matrix patches is recommended to evaluate the performance of this novel material and detect potential problems.

Mass spectrometry (MS) is considered today as one of the most popular detection methods, due to its high selectivity and sensitivity. In particular, this detector has become the gold standard for the analysis of complex mixtures such as biological samples. The first successful SFC-MS hyphenation was reported in the 80’s, and since then, several ionization sources, mass analyzers and interfacing technologies have been combined. Due to the specific physicochemical properties and compressibility of the SFC mobile phase, directing the column effluent into the ionization source is more challenging than in LC. Therefore, some specific interfaces have to be employed in SFC-MS, to i) avoid (or at least limit) analytes precipitation due to CO2 decompression, when the SFC mobile phase is not anymore under backpressure control, ii) achieve adequate ionization yield, even with a low proportion of MeOH in the mobile phase and iii) preserve the chromatographic integrity (i.e. maintaining retention, selectivity, and efficiency). The goal of this review is to describe the various SFC-MS interfaces and highlight the most favorable ones in terms of reliability, flexibility, sensitivity and user-friendliness.

In modern light-duty Diesel vehicles the particulate filters in the exhaust system require periodic regeneration to prevent plugging. The regeneration procedure is a major cause of dilution of engine oil with diesel fuel. In order to investigate the effect of the operation conditions of the engine on the fuel content in the oil, a precise and fast in-line measurement system is required. In this contribution a resonant sensor system for determination of diesel content by measuring the viscosity of the oil is tested. A commercial off-the-shelf quartz tuning fork resonator is used as sensor element and evaluated using a universal analyzer for resonant sensors developed for fast and precise acquisition of resonant sensor responses. The experiments presented in this paper show that fuel concentration in the range of 0.2 % can be determined within seconds. The obtained results are compared to that obtained with an accurate lab bench viscosity and mass density meter.

International audience; Comprehensive on-line two-dimensional liquid chromatography is an attractive technique to enhance peak capacity and deal with complex samples. Yet, its optimization is not straightforward and requires to take into account a huge number of parameters to finally obtain a good compromise between different criteria which are often conflicting. In this study, we propose a procedure for RPLC × RPLC separations able to define, for a given analysis time, the optimized LC × LC parameters for achieving the best compromise between high peak capacity and low dilution. This procedure makes use of both a prediction tool based on theoretical relationships and a Pareto-optimality approach to optimize these two criteria. The possibility to split the flow-rate of the first dimension before the interface is taken into account as well as the focusing effect in the second dimension. This optimization procedure is applied to the prediction of optimized conditions for the separation of peptides. The need for very short and efficient columns (typically 30 mm as column length and 1.3 μm as particle diameter) in the second dimension is clearly established whatever the geometry of the first dimension column. Furthermore it is shown that several sets of quite different conditions in the first dimension can lead to similar results and hence that additional quality descriptors are required to make a decision. RPLC × RPLC separations of a protein digest were carried out and the obtained results were found in very good accordance with the predicted ones. Our results were compared to the top results reported in the literature for 1D-RPLC separations of peptides. More than 4-fold increase in peak capacity (5100 vs 1150) at 200 min has been obtained. Furthermore a 40-fold gain in analysis time (1 h vs 40 h) was obtained for achieving 1800 as effective peak capacity which is close to the highest peak capacity reported in 1D-RPLC for the separation of peptides.

International audience; Comprehensive on-line two-dimensional liquid chromatography (LCxLC) is expected to generate impressive peak capacities, which makes it a method of choice for the analysis of complex samples such as pharmaceuticals. A comparative study of different sets of chromatographic conditions including stationary phase, pH additive and organic modifier was carried out with two real pharmaceutical samples in order to find out the best analytical conditions for implementation of one or several generic on-line LCxLC separations. Our choice was based on the evaluation of both degree of orthogonality and practical sample peak capacity under linear gradient conditions. The potential of 190 combinations of chromatographic systems was compared. A set of 3 RPLCxRPLC configurations was found to be very attractive for both samples and in good agreement with the findings of a previous study carried out with 17 model compounds, thereby supporting the idea of using generic LCxLC conditions in the pharmaceutical area. The three selected 2D-systems were implemented for the on-line RPLCxRPLC-UV/MS analysis of two pharmaceutical samples. It was shown, for each sample, that these 2D-systems were able to generate an effective peak capacity close to 1000 in less than 50min. For each sample, baseline separation was obtained for every known compound and furthermore a large number of unknown impurities could also be separated and identified. Finally, in the proposed conditions, the total number of compounds detected was significantly improved from one RPLC separation to one RPLCxRPLC separation. Only a small additional gain was observed by performing a second RPLCxRPLC separation or even a third one.

Artificial metalloenzymes, resulting from incorporation of a metal cofactor within a host protein, have received increasing attention in the last decade. The directed evolution is presented of an artificial transfer hydrogenase (ATHase) based on the biotin-streptavidin technology using a straightforward procedure allowing screening in cell-free extracts. Two streptavidin isoforms were yielded with improved catalytic activity and selectivity for the reduction of cyclic imines. The evolved ATHases were stable under biphasic catalytic conditions. The X-ray structure analysis reveals that introducing bulky residues within the active site results in flexibility changes of the cofactor, thus increasing exposure of the metal to the protein surface and leading to a reversal of enantioselectivity. This hypothesis was confirmed by a multiscale approach based mostly on molecular dynamics and protein-ligand dockings.

International audience; Extensive characterization of complex mixtures requires the combination of powerful analytical techniques. A Supercritical Fluid Chromatography (SFC) method was previously developed, for the specific case of fast pyrolysis bio oils, as an alternative to gas chromatography (GC and GC x GC) or liquid chromatography (LC and LC x LC), both separation methods being generally used prior to mass spectrometry (MS) for the characterization of such complex matrices. In this study we investigated the potential of SFC hyphenated to high resolution mass spectrometry (SFC-HRMS) for this characterization using Negative ion Atmospheric Pressure Chemical ionization (( - )APCI) for the ionization source. The interface between SFC and (-)APCI/HRMS was optimized from a mix of model compounds with the objective of maximizing the signal to noise ratio. The main studied parameters included both make-up flow-rate and make-up composition. A methodology for the treatment of APCI/HRMS data is proposed. This latter allowed for the identification of molecular formulae. Both SFC-APCI/HRMS method and data processing method were applied to a mixture of 36 model compounds, first analyzed alone and then spiked in a bio-oil. In both cases, 19 compounds could be detected. Among them 9 could be detected in a fast pyrolysis bio-oil by targeted analysis. The whole procedure was applied to the characterization of a bio-oil using helpful representations such as mass-plots, van Krevelen diagrams and heteroatom class distributions. Finally the results were compared with those obtained with a Fourier Transform ion-cyclotron resonance mass spectrometer (FT-ICR/MS)

The hemodynamic performance of artificial aortic valves (AVs) and the probability for structural valve deterioration can be linked to the valve kinematics. Comparability among different studies is limited because of variations in the experimental setups and physiologic boundary conditions. This study presents results of kinematic measurements of bioprosthetic and mechanical AVs that were tested in an identical experimental setting such that they can be directly compared with each other. The kinematics of AVs is typically presented in the form of the geometric orifice area and its temporal evolution. These parameters cannot capture asynchronous leaflet motion and out-of-plane leaflet velocity. In this work, each leaflet was tracked individually for a more detailed understanding of the leaflet kinematics, asynchronous leaflet motion, and leaflet tip velocities. A bioprosthetic valve, Edwards INTUITY (EINT), and two mechanical valves, Medtronic ADVANTAGE (MADV) and a Lapeyre-Triflo FURTIVA (TFUR), were tested in a compliant model of the aortic root in a physiologic flow loop. TFUR and MADV opened alike with maximum leaflet tip velocities of 0.77 and 0.66 m/s, respectively. The opening of EINT showed significantly higher local in-plane leaflet velocities of more than 2 m/s. EINT and TFUR exhibited similar early and slow closure. MADV closed significantly later with increased velocity. TFUR had a median maximum leaflet tip velocity of 0.39 m/s during valve closure and that of MADV was 0.83 m/s, whereas EINT exhibited a median maximum local in-plane leaflet velocity of 0.37 m/s. EINT experienced leaflet fluttering during systole with a flapping frequency of 36 Hz.

OBJECTIVE Coronary artery bypass grafting (CABG) remains the gold standard for complex revascularisation in multivessel disease. The concept of the minimally invasive extracorporeal circulation circuit (MiECC) was introduced to minimise pathophysiological side effects of conventional extracorporeal circulation. This study presents early and long-term outcomes after CABG with use of MiECC in a single-centre consecutive patient cohort. METHODS From 1 January 2005 to 31 December 2010, 2130 patients underwent isolated CABG with MiECC at our centre. We evaluated morbidity and mortality follow-up data with a median follow-up of 3.6 years. Kaplan-Meier curves and estimates of the primary end-point for all-cause mortality were compared with the life expectancy of the general population. RESULTS Mortality in CABG patients was comparable to the general population beginning 1 year after surgery for the whole observation period. All-cause 30-day mortality was 0.8%. The mean estimated logistic EuroSCORE and EuroSCORE II were 5.8 ± 8.6 and 3.0 ± 5.1, respectively. Mean perfusion time was 71.1 ± 23.8 min with a cross-clamp time of 44.9 ± 16.3 min. Mortality was predicted by the presence of diabetes mellitus (odds ratio [OR] 1.85, 95% confidence interval [CI] 1.40-2.46; p

This study was devoted to the search for conditions leading to highly efficient sub-hour separations of complex peptide samples with the objective of coupling to mass spectrometry. In this context, conditions for one dimensional reversed phase liquid chromatography (1D-RPLC) were optimized on the basis of a kinetic approach while conditions for on-line comprehensive two-dimensional liquid chromatography using reversed phase in both dimensions (on-line RPLCxRPLC) were optimized on the basis of a Pareto-optimal approach. Maximizing the peak capacity while minimizing the dilution factor for different analysis times (down to 5min) were the two objectives under consideration. For gradient times between 5 and 60min, 15cm was found to be the best column length in RPLC with sub-2μm particles under 800bar as system pressure. In RPLCxRPLC, for less than one hour as first dimension gradient time, the sampling rate was found to be a key parameter in addition to conventional parameters including column dimension, particle size, flow-rate and gradient conditions in both dimensions. It was shown that the optimum sampling rate was as low as one fraction per peak for very short gradient times (i.e. below 10min). The quality descriptors obtained under optimized RPLCxRPLC conditions were compared to those obtained under optimized RPLC conditions. Our experimental results for peptides, obtained with state of the art instrumentation, showed that RPLCxRPLC could outperform 1D-RPLC for gradient times longer than 5min. In 60min, the same peak intensity (same dilution) was observed with both techniques but with a 3-fold lower injected amount in RPLCxRPLC. A significant increase of the signal-to-noise ratio mainly due to a strong noise reduction was observed in RPLCxRPLC-MS compared to the one in 1D-RPLC-MS making RPLCxRPLC-MS a promising technique for peptide identification in complex matrices.

The universal genetic code is used by all life forms to encode biological information. It can also be used to encrypt semantic messages and convey them within organisms without anyone but the sender and recipient knowing, i.e., as a means of steganography. Several theoretical, but comparatively few experimental, approaches have been dedicated to this subject, so far. Here, we describe an experimental system to stably integrate encrypted messages within the yeast genome using a polymerase chain reaction (PCR)-based, one-step homologous recombination system. Thus, DNA sequences encoding alphabetical and/or numerical information will be inherited by yeast propagation and can be sent in the form of dried yeast. Moreover, due to the availability of triple shuttle vectors, Saccharomyces cerevisiae can also be used as an intermediate construction device for transfer of information to either Drosophila or mammalian cells as steganographic containers. Besides its classical use in alcoholic fermentation and its modern use for heterologous gene expression, we here show that baker's yeast can thus be employed in a novel Saccharomyces application (NSA) as a simple steganographic container to hide and convey messages.

International audience; Comprehensive on-line two-dimensional liquid chromatography (on-line LC × LC) was used for the characterization of bio-oils obtained by fast pyrolysis of lignocellulosic biomass. The resulting bio-oil contains a large number of oxygenated chemical families and must therefore be upgraded before being used as drop-in transportation biofuels. The good knowledge of its complex composition is essential for optimizing the mandatory bio-oil upgrading process to biofuels, thereby requiring powerful separation techniques designed to be hyphenated to mass spectrometry detection (LC × LC-MS). In this study, reversed phase conditions were optimized in both dimensions for the RPLC × RPLC separation of the aqueous fraction of bio-oils. The first step of method development consisted in searching for a suitable set of RP-conditions via the screening of a large number of RP-systems (made up of different stationary phases and/or mobile phases and/or temperature). The practical peak capacity and the degree of orthogonality were calculated for a sample of 38 representative compounds, both descriptors having been considered as selection criterion. Two different couplings were chosen and evaluated for the RPLC × RPLC separation of the 38 representative compounds. The best of both, in terms of real practical peak capacity, was further successfully applied to the separation of the aqueous phase of a partially dehydroxygenated bio-oil.

The performance of a recently introduced method to estimate the resonance parameters from complex spectral data and the error propagation for viscosity and density parameters of liquids are examined. The method is known to produce excellent results when used for piezoelectric and Lorentz force actuated sensors for single port or two-port devices. The method is also suited for very low quality factors (< 10) which extends the usable measurement range of many sensor concepts, especially for fluid sensing applications. Generally valid expressions for the measurement accuracy are stated and compared to measurement results obtained with a piezoelectric tuning fork and a Lorentz force actuated and inductively read out platelet sensor.

Most recently introduced viscosity and mass density sensors utilize vibrating resonant mechanical structures interacting with the sample fluid where the resonance frequency and the quality factor are affected by both, the fluid's viscosity and its mass density. Unlike singly clamped beams, straight, doubly clamped structures are advantageous when using electromagnetic excitation and read-out based on Lorentz forces which allow high excitation forces and read-out signals. However, classical straight beams such as bridges are subjected to high cross-sensitivities of their resonance frequencies to ambient temperature. To overcome high spurious temperature dependencies but to benefit from the straight doubly clamped approach, a spiral spring resonator applicable as viscosity and mass density sensor has been designed.

The principle of using steel tuning forks for viscosity and mass density measurements is investigated. From recorded frequency responses of fully immersed tuning forks, resonance frequencies and quality factors are evaluated and related to the liquids mass densities and viscosities. The benefit of these resonators is their mechanical rigidity which allows the application in harsh environments and mechanical cleaning processes without detuning or damaging the device. The setup was particularly devised that only the resonator itself but no excitation or read-out mechanisms get wetted by the sample liquid. The results obtained with a circular cross-sectioned tuning fork in different liquids are shown and discussed.

In this contribution we discuss a generalized, reduced order model for resonant viscosity and mass density sensors which considers also the devices’ cross sensitivities to temperature. The applicability of the model is substantiated by experimental results from measurements obtained with a circular steel tuning fork in various liquids and temperatures. Advantages of this model are its simplicity, its general applicability for resonant mass density and viscosity sensors which furthermore facilitates the comparison of different sensors.

International audience; In this second paper of a two-part series, on-line RPLC x HILIC is compared to on-line RPLC x RPLC through the separation of peptides. Our choices regarding the conditions are discussed. Injection effects and overloading effects are evaluated in both configurations. It is shown that whereas large volumes can be injected in the second dimension in RPLC x RPLC under HT-UHPLC conditions (>20% of the column dead volume), even small injection volumes (8% of the column the dead volume) have a detrimental effect on peak shapes in RPLC x HILIC. Advantages and limits of the two 2D-systems are compared through the 2D-separation of a tryptic digest of three proteins. A ten-fold gain in analysis time along with a significant gain in peak capacity are obtained with both systems compared to the most efficient one-dimensional separation of peptides recently published.

Objective Transcatheter aortic valve implantation gained clinical relevance with an impressive and peerless power; however, the procedure induces unsolved complications such as paravalvular leakage, occlusion of coronary ostia, and vascular complications. The safe removal of bulky calcified valves will improve the outcome, well known through the open surgical procedure. In this article, a new stapler-based resection and implantation device as well as a new approach for valve isolation during normal heart cycle without extracorporeal circulation will be analyzed. Methods First, a novel stapler-based instrument for transapical aortic valve replacement [removal and implantation; stapler-based aortic valve replacement (StapAVR)] was constructed and analyzed in an aortic debris model. Artificial aortic valves (N = 20), containing fluorescent granules to simulate the calcification, were placed into an aortic model in anatomical supine position (DP) and right-sided lateral position (RP). With the StapAVR, resection before implantation was performed in a water-filled basin. Black light was used for debris visualization. The procedures have been digitally recorded and analyzed due to procedural times, and the debris amount in thoracic side branches. Second, an enhanced prototype of the pulmonary valve isolation chamber (PVIC) was analyzed in porcine in vitro (n = 10) and in vivo models (n = 1). This PVIC contains a microaxial pump (Impella; Abiomed, Aachen, Germany) in the central bypass channel. It was deployed through the right ventricular wall. Once the PVIC was in place, the pump was started before isolating the valve. The complete hemodynamic monitoring was digitally recorded. Results The deployment of the StapAVR in the correct position and the valve resection time took a mean (SD) of 95.8 (19) seconds in DP and 90.1 (18) seconds in RP. Fluorescent debris was found: in the left coronary artery, 22% in DP and 7% in RP; in the ascending aorta, 0% in DP and 11% in RP; in the aortic bulbous, 5% in DP and 10% in RP; in the left ventricle, 8% in DP and 14% in RP; in the brachiocephalic trunk, 4% in DP and 9% in RP; and in the descending aorta, 46% in DP and 1% in RP. Consecutive valved stent implantation was performed without complications. The PVIC deployment time in vivo was 5 minutes, replacements included. The total valve isolation time was 21 minutes, with a mean (SD) bypass flow of 2.1 (0.4) L/min. The oxygen saturation showed a median of 91% (range, 83%–97%), and the median arterial blood pressure was 69 mm Hg (systolic; range, 47–120 mm Hg) and 40mm Hg (diastolic; range, 32–56 mm Hg) without the use of inotropes or vasopressors. Electrocardiogram confirmed sinus rhythm during isolation. Conclusions The resection of the artificial valves followed by valved stent implantation was possible with the StapAVR. In vivo, the procedure will be carried out under rapid pacing and sudden vacuum; however, the results of this in vitro debris model underline the need for isolation or filter devices during transcatheter aortic valve implantation to avoid embolization. Secondly, the use of the pump-advanced PVIC showed stable heart function for 21 minutes under isolated pulmonary valve conditions. This time will be adequate to remove bulky calcifications and to implant a valved stent. Improvements of both prototypes are ongoing. Nevertheless, the presented concepts showed promising application possibilities in the future.