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Abstract Background Primary coronary slow flow (CSF) is defined as delayed opacification of the distal epicardial vasculature during coronary angiography in the absence of relevant coronary artery stenoses. Microvascular disease is thought to be the underlying cause of this pathology. Epicardial fat tissue (EFT) is an active endocrine organ directly surrounding the coronary arteries that provides pro-inflammatory factors to the adjacent tissue by paracrine and vasocrine mechanisms. The aim of the present study was to investigate a potential association between EFT and primary CSF and whether EFT can predict the presence of primary CSF. Methods Between 2016 and 2017, n = 88 patients with high-grade aortic stenosis who were planned for transcatheter aortic valve implantation (TAVI) were included in this retrospective study. EFT volume was measured by pre-TAVI computed tomography (CT) using dedicated software. The presence of primary CSF was defined based on the TIMI frame count from the pre-TAVI coronary angiograms. Results Thirty-nine of 88 TAVI patients had CSF (44.3%). EFT volume was markedly higher in patients with CSF (142 ml [IQR 107–180] vs. 113 ml [IQR 89–147]; p = 0.009) and was strongly associated with the presence of CSF (OR 1.012 [95%CI 1.002–1.021]; p = 0.014). After adjustment, EFT volume was still an independent predictor of CSF (OR 1.016 [95%CI 1.004–1.026]; p = 0.009). Conclusion Primary CSF was independently associated with increased EFT volume. Further studies are needed to validate this finding and elucidate whether a causal relationship exists.

Aromatised wine-based beverages and regular wines are commonly bottled on the same bottling line. Sealings installed in the bottling line absorb added aroma compounds from the aromatised wine-based beverages and a subsequent release of the absorbed aroma compounds from the sealings was monitored during cleaning sequences and in subsequent products. Such unintentional carryover is associated with the risk of violating the legal ban of any aromatisation of regular wine. If cleaning is carried out according to good manufacturing practice (GMP) and traces of aroma compounds in the subsequently bottled wine show no sensory significance, this unintended aroma carryover will be considered by the German Federal Ministry of Nutrition and Agriculture as technically unavoidable and has no legal consequences. The risk of aroma absorption and aroma carryover have been investigated in different foods (orange juice, milk, and wine) and simulated in model systems using a beaker, but no real bottling scenario had been investigated till now. To fill the knowledge gap we investigated the potential aroma carryover in a pilot plant, and in two different wineries during three bottlings of aromatised wine-based beverages and subsequent regular sparkling wine. Monitoring of installed sealings revealed the uptake of seven aroma compounds and further release of aroma compounds during a recommended cleaning sequence and subsequent contact with wine. A sensory significant aroma carryover into the subsequent wine that had been circulating for 24 hours in the pilot plant was observed only for α-ionone, which exceeded its odour detection threshold in white wine after 8 hours. Regarding the three bottlings of aromatised wine-based beverages and the subsequent sparkling wine, we recorded the uptake of γ-decalactone, eugenol, and trans-cinnamaldehyde in the sealings, and their further diminishment during the implemented cleaning of the wineries and subsequent bottling of a sparkling wine. During the short residence time of the product in the bottling line, no sensory and analytical differentiation of the pre-bottled and bottled sparkling wines was observed.

Modeling and simulation lie at the heart of the design process of any nuclear application. An accurate representation of the radiation environment ensures not only the feasibility of new technologies, but it also aids in operation, maintenance, and even decommissioning. With increasingly complex designs, high-fidelity models have become a necessity for design maturity. McCAD has been under development for many years at Karlsruhe Institute of Technology (KIT) to facilitate the process of generating suitable models for nuclear analyses. In this paper, an overview of the major advances in the new version of the code is presented. A novel conversion algorithm has proven to be robust in significantly reducing the processing time to generate radiation transport models, making it easier to iterate on design details. A first-of-a-kind capability to generate hierarchical void cells is also discussed with preliminary analysis showing performance gains for particle tracking.

Abstract Background Cardiovascular magnetic resonance (CMR) plays a pivotal role in diagnosing myocardial inflammation. In addition to late gadolinium enhancement (LGE), native T1 and T2 mapping as well as extracellular volume (ECV) are essential tools for tissue characterization. However, the differentiation of cardiac sarcoidosis (CS) from myocarditis of other etiology can be challenging. Positron-emission tomography-computed tomography (PET-CT) regularly shows the highest Fluordesoxyglucose (FDG) uptake in LGE positive regions. It was therefore the aim of this study to investigate, whether native T1, T2, and ECV measurements within LGE regions can improve the differentiation of CS and myocarditis compared with using global native T1, T2, and ECV values alone. Methods PET/CT confirmed CS patients and myocarditis patients (both acute and chronic) from a prospective registry were compared with respect to regional native T1, T2, and ECV. Acute and chronic myocarditis were defined based on the 2013 European Society of Cardiology position paper on myocarditis. All parametric measures and ECV were acquired in standard fashion on three short-axis slices according to the ConSept study for global values and within PET-CT positive regions of LGE. Results Between 2017 and 2020, 33 patients with CS and 73 chronic and 35 acute myocarditis patients were identified. The mean ECV (± SD) in LGE regions of CS patients was higher than in myocarditis patients (CS vs. acute and chronic, respectively: 0.65 ± 0.12 vs. 0.45 ± 0.13 and 0.47 ± 0.1; p

AimsCardiac decompensation (CD) in patients with aortic stenosis is a “red flag” for future adverse events. We classified patients undergoing transcatheter aortic valve implantation (TAVI) into those with acute, prior, or no prior CD at the timepoint of TAVI and compared their clinical presentation, prognosis, and effects of the prescribed medication during follow-up.MethodsRetrospective analysis of patients of one center fulfilling the criteria of 30-day device success after transfemoral TAVI.ResultsFrom those patients with no CD (n = 1,985) ranging to those with prior CD (n = 497) and to those with acute CD (n = 87), we observed a stepwise increase in the proportion of patients in poor clinical condition, NYHA class III/IV, low psoas muscle area, fluid overload (rales, oedema, pleural effusion), reduced ejection fraction, renal insufficiency, and anemia. More diuretics but less renin-angiotensin system inhibitors (ACEI/ARB) were prescribed for patients with acute CD compared to other groups. Prior CD (hazard ratio and 95% CI 1.40; 1.02–1.91) and acute CD (1.72; 1.01–2.91), a reduced general condition (1.53; 1.06–2.20), fluid overload (1.54;1.14–2.08), atrial fibrillation (1.76; 1.32–2.33), and anemia (1.43;1.08–1.89) emerged as strong independent predictors of one-year mortality. In all three classes of CD, prescribing of ACEI/ARB was associated with a substantial improvement of survival.ConclusionsThe clinical presentation of (acute or prior) cardiac decompensation in patients with AS overlapped substantially with that of patients with classical signs of heart failure. Our results may support an early treatment strategy in patients with left ventricular dysfuntion before clinical signs of congestion are manifest. Moreover, these patients require intensive medical attention after TAVI.

Climate change is an environmental challenge that impacts the wine industry due to frequent sunburn damage triggered by heat waves, sun radiation and severe water deficits. This leads to severe yield losses and sensory changes in the resulting wines, presumably caused by climate-induced off-flavours. This study aims to develop viticultural and oenological strategies to mitigate sunburn damage in the highly sensitive variety Riesling and its detrimental sensory properties. In 2020, we combined the timing and intensity of defoliation measures with the application of kaolin and calcium hydroxide suspensions, reflecting a portion of the solar radiation. Seven treatments were replicated in three field experiments. Grapes from each field replication were maintained as a fermentation replication and, therefore, separately vinified following a standardised protocol. Replicates, including field and fermentation replicates, were further used as sensory replications. Descriptive analysis (DA) and temporal dominance of sensations (TDS) revealed a significant sensory impact of experimental trials in eight of twelve attributes. Additionally, wines were analysed by gas chromatography-mass spectrometry. The early sun exposition treatment with partial defoliation of the grape zone after flowering, followed by a second defoliation at berry closure, reduced fruity aroma but increased smoky notes due to enhanced 4-vinylguajacol formation as well as the intensity of the atypical ageing note (ATA) reminiscent of acacia blossom, naphthalene and fusel alcohols. Applying kaolin or calcium hydroxide particles on the berry skin slightly mitigated these unpleasant effects and even increased fruitiness and sweetness. Late defoliation at berry closure diminished the green note, which was most prominent in the non-defoliated control. Further smokiness and ATA intensities were lowered, in contrast to their rise due to early defoliation. However, late defoliation increased 1,1,6-trimethyl-1,2-dihydronaphthalene (TDN), causing the petrol off-flavour. TDS analysis revealed a higher fruity and sweet dominance during the first 10 seconds due to early defoliation, while late defoliation fostered dominant and lingering sourness. In conclusion, early defoliation, which lowers sunburn incidence due to an early adaptation towards sun exposure, increases smoky and ATA flavours and diminishes fruitiness. These detrimental sensory effects could be significantly mitigated by applying reflecting particles of kaolin and calcium hydroxide on berry skins.

The absorption of aroma compounds in seals during the bottling of wine and the migration of these aroma compounds into the subsequent bottling process is a major problem in the German wine industry. In order to meet the legal requirements, for example, the seals used up to now have to be replaced with more expensive alternatives. However, these alternatives are not suitable for every area of application. An alternative to this is the use of modified ethylene-propylene-diene-rubber seals, which have a lower aroma compound carry-over. In a research project, new and inexpensive ethylene-propylene-diene-rubber seals were developed which minimise migration into the subsequent filling process. The seal material and the surface of the seals were modified. Within the scope of the research, compounds of different fillers were prepared and examined for their migration properties of critical aroma compounds. Furthermore, the influence of the degree of crosslinking, the ethylene content of the basic rubbers used, the plasticisers used and the influence of the surface roughness of the seals were also examined. The seals were coated using low-pressure plasma in order to describe the migration of selected aroma compounds depending on the surface properties. In addition to the migration properties, the influence of the fillers used on mechanical properties such as elongation at break and compression set was also measured, since seals have to fulfil a wide range of requirements. By means of statistical test planning, the observation was carried out in effect and contour diagrams in order to create an optimised sealing material on the basis of the resources used.

BackgroundHigh-grade AV block (HAVB) is the most frequent adverse event after transcatheter aortic valve implantation (TAVI). In rare cases, HAVB is associated with hemodynamic compromise (HC) followed by syncope or application of cardiopulmonary resuscitation (CPR), but data on this severe complication are scarce. The aim of the present study was to investigate the incidence and predictors of HC due to HAVB in patients undergoing TAVI.MethodsIn this retrospective analysis of 4,602 TAVI cases between 2010 and 2022, 466 developed HAVB. Baseline characteristics and procedural and postprocedural findings were compared for patients with HC versus those without. Univariate and multivariable regression analyses were used to investigate independent predictors of HC.ResultsForty-nine of 466 patients (10.5%) had HC due to HAVB after TAVI. Patients with HC had a longer hospital stay [10 (8–13) vs. 13 (9–18) days; p

BackgroundNative T1 has become a pivotal parameter of tissue composition that is assessed by cardiac magnetic resonance (CMR). It characterizes diseased myocardium and can be used for prognosis estimation. Recent publications have shown that native T1 is influenced by short-term fluctuations of volume status due to hydration or hemodialysis.MethodsPatients from a prospective BioCVI all-comers clinical CMR registry were included, and native T1 and plasma volume status (PVS) were determined according to Hakim’s formula as surrogate markers of patient volume status. The primary endpoint was defined as combined endpoint of cardiovascular death or hospitalization for heart failure events, the secondary endpoint was defined as all-cause mortality.ResultsA total of 2,047 patients were included since April 2017 [median (IQR); age 63 (52–72) years, 33% female]. There was a significant although weak influence of PVS on native T1 (β = 0.11, p −13%) showed significantly higher values for tissue markers than non-volume-overloaded patients [PVS ≤ −13%; median (IQR); native T1 1,130 (1,095–1,170) vs. 1,123 (1,086–1,166) ms, p

Comprehensive yeast strain characterization is an important issue for the wine industry as market demands require controlled production of distinctive high-quality wines. Glycosides form an important reservoir of varietal grape wine aroma, and their hydrolysis into olfactory-active compounds essentially depends on the fermenting yeast genera and strains. Among the 14 Metschnikowia, Pichia, Torulaspora and 18 Saccharomyces spp., rapid screenings by agar plate and activity assay, including the substrates arbutin, cellobiose and p-nitrophenol-β-D-glucopyranoside, revealed the most glycosidase-active strains. In the novel co-fermentation setups, five selected non-Saccharomyces and a Saccharomyces strain were separated by a 14 kDa cut-off membrane, allowing respective viable cell counts but facilitating metabolite transfer. Chemical analysis focused on aroma glycosides, with extensive quantification by GC-MS with SIDA on the extracted and hydrolyzed compounds. Olfactory profiles obtained for the non-Saccharomyces wines demonstrated a significant impact of these yeasts, albeit mainly correlated with increased hydrolysis of monoterpene glycosides, and surpassed by a technical Aspergillus niger enzyme. While screenings of non-Saccharomyces strains indicated enhanced glucosidase activity under winemaking conditions, their effect was lower than expected and dominated by ester formation. Interestingly, Saccharomyces yeast cell vitality was increased via in co-fermentation, and non-Saccharomyces strains displayed extended viabilities with high ethanol tolerances.

Background In chronic thromboembolic pulmonary hypertension, right heart failure determines outcome. Balloon pulmonary angioplasty therapy allows right heart recovery, which can be monitored by cardiac magnetic resonance imaging. This study evaluates whether cardiac biomarkers (NT‐proBNP, MR‐proANP, sST2, and PAPP‐A) are associated with cardiac magnetic resonance imaging findings prior to and after balloon pulmonary angioplasty therapy. Methods This observational cohort study enrolled 22 chronic thromboembolic pulmonary hypertension patients who underwent balloon pulmonary angioplasty therapy and completed a six‐month follow‐up including cardiac magnetic resonance imaging. Biomarker levels were compared with findings for right heart morphology and function derived from cardiac magnetic resonance imaging. Results Pulmonary hemodynamics improved after balloon pulmonary angioplasty therapy [pulmonary vascular resistance: 7.7 (6.0–9.0) vs. 4.7 (3.5–5.5) wood units, p

Bottling of aromatised wines and regular table wines often takes place on the same bottling line. Installed sealings in the bottling line absorb volatiles from aromatised wines and, due to inadequate cleaning, carryover occurs into the subsequently bottled regular wine. This unintentional carryover can lead to accusations of illegal flavouring of wine. To minimise the carryover risk, sealing materials that absorb less volatiles are beneficial. Incorporating kaolin and micro-cellulose into the ethylene propylene diene monomer rubber (EPDM) network decreased absorption of the critical α-ionone by 51 and 60 %, respectively. Besides the minimisation of the absorption, a performed cleaning can reduce aroma carryover. So far, knowledge about cleaning parameters that can increase cleaning efficiency is limited since cleaning usually focuses on surficial removal and prevents microbiological cross-contamination. An evaluation of the cleaning parameters, temperature, time and agents clearly revealed a high factor in the considered temperature. The highest cleaning efficiency was seen at 85 °C, whereas the cleaning additives such as citric acid, caustic soda, ozone or dissolved carbon dioxide had no impact. High proportions of the aroma compounds were removed from the polymer in the first 20 min at 85 °C, but none of the performed cleaning sequences was able to remove all compounds.

Myocardial inflammation and edema are major pathological features in myocarditis. Myocardial tissue water content and myocardial edema can be quantified via T2 mapping. Thus, cardiac magnetic resonance (CMR) is the noninvasive gold standard for diagnosing myocarditis. Several studies showed an impact of short-term volume changes on T2 relaxation time. Plasma volume status (PVS) is a good surrogate parameter to quantify a patient’s volume status, and it is simple to use. The aim of this study was to determine the effect of PVS on the diagnostic value of T2 relaxation time in myocardial inflammation. Between April 2017 and December 2022, patients who were indicated for cardiac CMR were included in our prospective clinical registry. Patients with myocardial inflammation and those with unremarkable findings were analyzed in the present study. A blood sample was drawn, and PVS was calculated. Patients were separated into PVS tertiles to explore a possible nonlinear dose–response relationship. Logistic regression analysis was used to determine whether T2 is an independent predictor of myocardial inflammation. A total of 700 patients (47.43% female) were eligible for analysis. Of these, 551 patients were healthy (78.7%), while 149 (21.3%) showed signs of myocardial inflammation. The T2 relaxation time was elevated in patients with myocardial inflammation (40 ms [IQR 37–42 ms] vs. 38.0 ms [IQR 36–39 ms], p < 0.001). PVS showed no difference between the groups (−12.94 [IQR −18.4–−7.28] vs.−12.19 [IQR −18.93–−5.87], p = 0.384). T2 showed a clear dose–response relationship with PVS, with increasing T2 values along the PVS tertiles. In spite of this, T2 was found to be an independent marker of myocardial inflammation in logistic regression (OR T2 1.3 [95% CI 1.21–1.39], p < 0.001), even after adjusting for PVS (OR T2 [adj. PVS] 1.31 [95% CI 1.22–1.40], p < 0.001). Despite a dose–response relationship between T2 and the volume status, T2 was found to be an independent indicator of myocardial inflammation.

Cardiac magnetic resonance (CMR) is currently the gold standard for evaluating right ventricular (RV) function, which is critical in patients with pulmonary hypertension. CMR feature-tracking (FT) strain analysis has emerged as a technique to detect subtle changes. However, the dependence of RV strain on load is still a matter of debate. The aim of this study was to measure the afterload dependence of RV strain and to correlate it with surrogate markers of contractility in a cohort of patients with chronic thromboembolic pulmonary hypertension (CTEPH) under two different loading conditions before and after pulmonary endarterectomy (PEA). Between 2009 and 2022, 496 patients with 601 CMR examinations were retrospectively identified from our CTEPH cohort, and the results of 194 examinations with right heart catheterization within 24 h were available. The CMR FT strain (longitudinal (GLS) and circumferential (GCS)) was computed on steady-state free precession (SSFP) cine CMR sequences. The effective pulmonary arterial elastance (Ea) and RV chamber elastance (Ees) were approximated by dividing mean pulmonary arterial pressure by the indexed stroke volume or end-systolic volume, respectively. GLS and GCS correlated significantly with Ea and Ees/Ea in the overall cohort and individually before and after PEA. There was no general correlation with Ees; however, under high afterload, before PEA, Ees correlated significantly. The results show that RV GLS and GCS are highly afterload-dependent and reflect ventriculoarterial coupling. Ees was significantly correlated with strain only under high loading conditions, which probably reflects contractile adaptation to pulsatile load rather than contractility in general.

High-performance countercurrent chromatography (HPCCC) was used for the target-guided isolation of precursors of 1,1,6-trimethyl-1,2-dihydronaphthalene (TDN) from Riesling wine. In separated HPCCC fractions of an Amberlite® XAD®-2 extract obtained from a German Riesling, TDN-generating fractions were identified by the acid-catalyzed hydrolysis of the progenitors at pH 3.0 and subsequent HS-GC-MS/MS analysis. The presence of multiple TDN-generating precursors in Riesling wine could be confirmed. From polar HPCCC fractions (11–13 and 14–16), 3,4-dihydroxy-7,8-dihydro-β-ionone 3-O-rutinoside and 3,4-dihydroxy-7,8-dihydro-β-ionone 3-O-β-d-glucopyranoside were isolated as major TDN-precursors at a sufficient amount for structure elucidation by NMR spectroscopic studies. In the medium polar HPCCC factions (27–35), enzymatic hydrolysis liberated the aglycones 3-hydroxy-β-ionone and 3-hydroxy-TDN in minor amounts. In further less polar TDN-generation fractions (36–44 and 45–50), glycosidic progenitors were absent; instead, a minor TDN formation most likely from non-conjugated constituents was observed.

BackgroundTranscatheter aortic valve implantation (TAVI) is the standard treatment option for patients with severe aortic stenosis (AS) at intermediate or high surgical risk. Preexisting right bundle branch block (RBBB) is a strong predictor of new pacemaker implantation (PPM) after TAVI, and previous data indicate a worse short- and long-term outcome of patients. The aim of this study was to investigate whether preexisting RBBB has an effect on the short- and mid-term outcome of patients undergoing TAVI in a German high-volume TAVI center.MethodsFor the present retrospective analysis, a total of 1,891 patients with native severe AS with successful TAVI without preexisting PPM were included. The primary endpoint was all-cause mortality after 30 days and 12 months. Baseline RBBB was present in 190 (10.1%) of cases.ResultsPatients with preexisting RBBB had a considerably higher rate of new PPM after TAVI compared with patients without RBBB (87/190 [45.8%] vs. 219/1,701 [12.9%]; pConclusionPreexisting RBBB is a common finding in patients with severe AS undergoing TAVI and is associated with considerably higher PPM rates but not with worse short- and mid-term outcome.

Background Chronic thromboembolic pulmonary hypertension (CTEPH) leads to right heart failure. Pulmonary endarterectomy (PEA) or balloon pulmonary angioplasty (BPA) restore pulmonary haemodynamics and allow cardiac recovery. This study examined the relationship of copeptin and mid-regional pro-atrial natriuretic peptide (MR-proANP) levels to disease severity and therapy response. Methods This observational cohort study included 125 patients (55 PEA/70 BPA) who underwent treatment and completed a 6-/12-month follow-up. Biomarkers, measured at baseline, prior to every BPA and at follow-up, were compared to 1) severe disease at baseline (right atrial pressure (RAP) ≥8 mmHg and cardiac index ≤2.4 L·min−1·m−2) and 2) optimal therapy response (no persistent pulmonary hypertension combined with a normalised RAP (mean PAP ≤25 mmHg, pulmonary vascular resistance (PVR) ≤3 WU and RAP ≤6 mmHg) or a reduction in mean PAP ≥25%, PVR ≥35% and RAP ≥25%). Results Severely diseased patients had higher levels of MR-proANP (320 (246–527) pmol·L−1 versus 133 (82–215) pmol·L−1; p=0.001) and copeptin (12.7 (7.3–20.6) pmol·L−1 versus 6.8 (4.4–12.8) pmol·L−1; p=0.015) at baseline than the rest of the cohort. At baseline, MR-proANP (area under the curve (AUC) 0.91; cut-off value 227 pmol·L−1; OR 56, 95% CI 6.9–454.3) and copeptin (AUC 0.70; cut-off value 10.9 pmol·L−1; OR 1.5, 95% CI 1.2–1.9) identified severely diseased patients. After PEA/BPA, levels of MR-proANP (99 (58–145) pmol·L−1; p

IFMIF-DONES (International Fusion Materials Irradiation Facility - DEMO-oriented Neutron Source) is currently being developed in the frame of the EUROfusion Early Neutron Source work package (WPENS), based on the results achieved in the ongoing IFMIF/EVEDA (Engineering Validation and Engineering Design Activities) project by Japan and Europe in the frame of the Braoder Approach (BA) agreement. The neutron source's limited product of “irradiation volume × neutron fluence” on one hand and the large potential test matrix (defined by number of material grades, test types, irradiation- and test temperature levels and damage dose levels) on the other hand, require a careful selection of test conditions by collaborative effort of the communities of DEMO designers, fusion materials science and the irradiation facility designers. This paper describes achievable irradiation conditions in the High Flux Test Module (HFTM) of IFMIF-DONES, characterized by levels and gradients of irradiation temperatures and nuclear responses (dpa, H and He production). The HFTM development focuses on 9%-Cr Reduced Activation Ferritic Martensitic steel irradiations, but also the possibilities of tungsten and copper alloy irradiations are explored. Possible specimen arrangements and issues of the Small Specimens Test Technique are also discussed.

IFMIF-DONES (International Fusion Materials Irradiation Facility- DEMO Oriented NEutron Source) is a neutron irradiation facility aiming at providing material irradiation data for the construction of DEMOnstration fusion power plants. This work presents nuclear analyses and associated neutronics modeling conducted on an updated design of the High Flux Test Module (HFTM) of IFMIF-DONES. Neutron fluxes, damage dose rates and gradients, gas production and nuclear heating have been calculated for the standard profile in 20 × 5 cm2 and a reduced size in 10 × 5 cm2 of the deuteron beam with 40 MeV energy and 125 mA current. The results indicate that the reduced beam can provide higher damage dose rates fulfilling the DONES requirement. On the other hand, the reduced beam size results in less irradiation uniformity, higher gas production to damage dose ratios, as well as stronger peak nuclear heating. Keywords: IFMIF-DONES, HFTM, Neutronics, DPA, gas production

Although there is an extensive tradition of research into the microbes that underlie the winemaking process, much remains to be learnt. We combined the high-throughput sequencing (HTS) tools of metabarcoding and metagenomics, to characterize how microbial communities of Riesling musts sampled at four different vineyards, and their subsequent spontaneously fermented derivatives, vary. We specifically explored community variation relating to three points: (i) how microbial communities vary by vineyard; (ii) how community biodiversity changes during alcoholic fermentation; and (iii) how microbial community varies between musts that successfully complete alcoholic fermentation and those that become ‘stuck’ in the process. Our metabarcoding data showed a general influence of microbial composition at the vineyard level. Two of the vineyards (4 and 5) had strikingly a change in the differential abundance of Metschnikowia. We therefore additionally performed shotgun metagenomic sequencing on a subset of the samples to provide preliminary insights into the potential relevance of this observation, and used the data to both investigate functional potential and reconstruct draft genomes (bins). At these two vineyards, we also observed an increase in non-Saccharomycetaceae fungal functions, and a decrease in bacterial functions during the early fermentation stage. The binning results yielded 11 coherent bins, with both vineyards sharing the yeast bins Hanseniaspora and Saccharomyces. Read recruitment and functional analysis of this data revealed that during fermentation, a high abundance of Metschnikowia might serve as a biocontrol agent against bacteria, via a putative iron depletion pathway, and this in turn could help Saccharomyces dominate the fermentation. During alcoholic fermentation, we observed a general decrease in biodiversity in both the metabarcoding and metagenomic data. Unexpected Micrococcus behavior was observed in vineyard 4 according to metagenomic analyses based on reference-based read mapping. Analysis of open reading frames using these data showed an increase of functions assigned to class Actinobacteria in the end of fermentation. Therefore, we hypothesize that bacteria might sit-and-wait until Saccharomyces activity slows down. Complementary approaches to annotation instead of relying a single database provide more coherent information true species. Lastly, our metabarcoding data enabled us to identify a relationship between stuck fermentations and Starmerella abundance. Given that robust chemical analysis indicated that although the stuck samples contained residual glucose, all fructose had been consumed, we hypothesize that this was because fructophilic Starmerella, rather than Saccharomyces, dominated these fermentations. Overall, our results showcase the different ways in which metagenomic analyses can improve our understanding of the wine alcoholic fermentation process.

AIMS:Patients with aortic stenosis (AS) may have concomitant heart failure (HF) that determines prognosis despite successful transcatheter aortic valve implantation (TAVI). We compared outcomes of TAVI patients with low stroke volume index (SVI) ≤35 ml/m2 body surface area in different HF classes. METHODS AND RESULTS:Patients treated by transfemoral TAVI at our center (n = 1822) were classified as 1) 'HF with preserved ejection fraction (EF)' (HFpEF, EF ≥50%), 2) 'HF with mid-range EF' (HFmrEF, EF 40-49%), or 3) 'HF with reduced EF' (HFrEF, EF 35 ml/m2 served as controls. The prevalence of cardiovascular disease and symptoms increased stepwise from controls (n = 968) to patients with HFpEF (n = 591), HFmrEF (n = 97), and HFrEF (n = 166). Mortality tended to be highest in HFrEF patients 30 days post-procedure, and it became significant after one year: 10.2% (controls), 13.5% (HFpEF), 13.4% (HFmrEF), and 23.5% (HFrEF). However, symptomatic improvement in survivors of all groups was achieved in the majority of patients without differences among groups. CONCLUSIONS:Patients with AS and HF benefit from TAVI with respect to symptom alleviation. TAVI in patients with HFpEF and HFmrEF led to an identical, favorable post-procedural prognosis that was significantly better than that of patients with HFrEF, which remains a high-risk population.

The IFMIF-DONES (International Fusion Material Irradiation Facility-DEMO Oriented NEutron Source) facility is being designed with the general objective of providing irradiation of representative samples of power fusion machine materials under prototypical conditions. A linear accelerator will deliver deuterons at high intensity to circulating lithium in a loop, which will produce neutrons capable of obtaining the required damage conditions. As a result of this process, radionuclides will be produced as a by-product, which is characterized by several degrees of mobility. Shielding and radiation protection measures will be required in the facility. IFMIF-DONES will be classified as a first class radioactive facility according to national regulations, with Spain being the European candidate to site the facility. Several aspects of the main safety instructions affecting the facility’s design are explained and discussed in this paper.

Most yeast and bacteria in wine are able to metabolize hydroxycinnamic acids into volatile phenols via enzyme-mediated decarboxylation. Our trials performed in wine and model systems suggest that lysozyme addition prior to fermentation affects both bacterial activity and the release of hydroxycinnamic acids from their tartrate esters. This increases the potential for volatile phenol formation, as microorganisms can only metabolize free hydroxycinnamates. Wines with delayed malolactic fermentation due to lysozyme addition contained significantly higher concentrations of free hydroxycinnamic acids and elevated levels of volatile phenols in some cases. The reason for this is likely related to the side activity of lysozyme in combination with a detoxification mechanism that only occurs under stressful conditions for the yeast. Experiments in model systems indicate that lysozyme can affect the yeast at a pH higher than usually found in wine by attacking chitin in the bud scars of the cell walls and therefore weakening the cell structure. Free hydroxycinnamates can also affect yeast viability, making an increased release during fermentation problematic for a successful fermentation.

Prognosis of patients with heart failure remains poor despite improved conventional and interventional treatment regimens. The improvement of neovascularization and repair processes by administration of bone marrow-derived cells modestly improved the recovery after acute myocardial infarction. However, circulating patient-derived cells are reduced in number and function particularly in chronic heart failure. Therefore, we tested the hypothesis whether the mobilization of circulating mononuclear proangiogenic cells (CPCs) by G-CSF may overcome some of these limitations. In the present pilot study, 32 patients with at least 3-month-old myocardial infarction were randomized to G-CSF alone (G-CSF group) or intracoronary infusion of G-CSF-mobilized and cultured CPCs into the infarct-related artery (G-CSF/CPC group). Primary endpoint of the study was safety. Efficacy parameters included serial assessment of LV function, NT-proBNP levels, and cardiopulmonary exercise testing. G-CSF effectively mobilized circulating CD34 + CD45 + cells after 5 days in all patients (408 ± 64%) without serious adverse events. At 3 months, NYHA class and global LV function did not show significant improvements in both treatment groups (G-CSF: ΔLVEF 1.6 ± 2.4%; p = 0.10; G-CSF/CPC: ΔLVEF 1.4 ± 4.1%; p = 0.16). In contrast, target area contractility improved significantly in the G-CSF/CPC group. During 5-year follow-up, one patient died after rehospitalization for worsening heart failure. Eleven patients underwent further revascularization procedures. NT-proBNP levels, cardiopulmonary exercise capacity, and NYHA class remained stable in both treatment groups. The results from our pilot trial indicate that administration of G-CSF alone or G-CSF-mobilized and cultured CPCs can be performed safely in patients with chronic ischemic heart disease. However, only minor effects on LV function, NT-proBNP levels, and NYHA classification were observed during follow-up, suggesting that the enhancement of CPCs by G-CSF alone does not substantially improve intracoronary cell therapy effects in patients with chronic ischemic heart failure.

The rapid and complete characterization of chemical reaction mechanisms and their associated heat production is of the utmost importance in terms of chemical understanding and process safety and efficiency. In this contribution a new small volume (25–50 ml) combined reaction calorimeter (CRC) will be described. With this reactor it is possible to make calibration free calorimetry measurements and in situ mid-IR measurements simultaneously as well as gas consumption/production measurements in pressure-proof versions. The application of this reactor to the industrially relevant solvent free esterification of 1-butanol by acetic anhydride followed using calorimetry and mid-IR spectroscopy (a common reaction in the synthesis of many solvents, pharmaceuticals and perfumes) will be demonstrated. The results for this chemical system are presented in conjunction with a description of data analysis techniques allowing kinetic model fitting simultaneously to the different types of in situ measurements.

As a result of legislation and increasing public awareness, environmental considerations are given more and more importance in chemical process design. Furthermore, the focus in environmental protection has shifted from end-of-pipe technologies to improvements of the chemical processes. The realization of such improvements, on one hand, requires chemical or technical innovations (new molecules, new synthesis routes, new process designs) and, on the other hand, assessment methods are needed that deliver an objective comparison of process alternatives on appropriately defined system boundaries.Four different indicators for assessing the environmental impact of chemical processes are discussed: Mass Loss Indices (MLI), Environmental Indices (EI), a comprehensive EHS (Environment, Health, and Safety) assessment method, and Eco-Indicator 95, an evaluation method used in the Life Cycle Analysis (LCA) framework. These methods are summarized, compared, and applied to case studies from the chemical industry. Finally, the corresponding results are discussed and conclusions on the capability and limitations of the different indicators are drawn, in particular with regard to their applicability during the early phases of process development.