Spatial variability in herbaceous plant phenology is mostly explained by variability in temperature but also by photoperiod and functional traits.

Whereas temporal variability of plant phenology in response to climate change has already been well studied, the spatial variability of phenology is not well understood. Given that phenological shifts may affect biotic interactions, there is a need to investigate how the variability in environmental factors relates to the spatial variability in herbaceous species' phenology by at the same time considering their functional traits to predict their general and species-specific responses to future climate change. In this project, we analysed phenology records of 148 herbaceous species, which were observed for a single year by the PhenObs network in 15 botanical gardens. For each species, we characterised the spatial variability in six different phenological stages across gardens. We used boosted regression trees to link these variabilities in phenology to the variability in environmental parameters (temperature, latitude and local habitat conditions) as well as species traits (seed mass, vegetative height, specific leaf area and temporal niche) hypothesised to be related to phenology variability. We found that spatial variability in the phenology of herbaceous species was mainly driven by the variability in temperature but also photoperiod was an important driving factor for some phenological stages. In addition, we found that early-flowering and less competitive species characterised by small specific leaf area and vegetative height were more variable in their phenology. Our findings contribute to the field of phenology by showing that besides temperature, photoperiod and functional traits are important to be included when spatial variability of herbaceous species is investigated.

Varroa Mite Counting Based on Hyperspectral Imaging.

Varroa mite infestation poses a severe threat to honeybee colonies globally. This study investigates the feasibility of utilizing the HS-Cam and machine learning techniques for Varroa mite counting. The methodology involves image acquisition, dimensionality reduction through Principal Component Analysis (PCA), and machine learning-based segmentation and classification algorithms. Specifically, a k-Nearest Neighbors (kNNs) model distinguishes Varroa mites from other objects in the images, while a Support Vector Machine (SVM) classifier enhances shape detection. The final phase integrates a dedicated counting algorithm, leveraging outputs from the SVM classifier to quantify Varroa mite populations in hyperspectral images. The preliminary results demonstrate segmentation accuracy exceeding 99% and an average precision of 0.9983 and recall of 0.9947 across all the classes. The results obtained from our machine learning-based approach for Varroa mite counting were compared against ground-truth labels obtained through manual counting, demonstrating a high degree of agreement between the automated counting and manual ground truth. Despite working with a limited dataset, the HS-Cam showcases its potential for Varroa counting, delivering superior performance compared to traditional RGB images. Future research directions include validating the proposed hyperspectral imaging methodology with a more extensive and diverse dataset. Additionally, the effectiveness of using a near-infrared (NIR) excitation source for Varroa detection will be explored, along with assessing smartphone integration feasibility.

Microbiota and Nutrient Portraits of European Roe Deer (Capreolus capreolus) Rumen Contents in Characteristic Southern German Habitats.

Roe deer (Capreolus capreolus) are found in various habitats, from pure forest cultures to agricultural areas and mountains. In adapting to the geographically and seasonally differentiating food supply, they depend, above all, on an adapted microbiome. However, knowledge about the microbiome of wild ruminants still needs to be improved. There are only a few publications for individual species with a low number of samples. This study aims to identify a core microbiota for Bavarian roe deer and present nutrient and microbiota portraits of the individual habitat types. This study investigated the roe deer's rumen (reticulorumen) content from seven different characteristic Bavarian habitat types. The focus was on the composition of nutrients, fermentation products, and the rumen bacterial community. A total of 311 roe deer samples were analysed, with the most even possible distribution per habitat, season, age class, and gender. Significant differences in nutrient concentrations and microbial composition were identified for the factors habitat, season, and age class. The highest crude protein content (plant protein and microbial) in the rumen was determined in the purely agricultural habitat (AG), the highest value of non-fibre carbohydrates in the alpine mountain forest, and the highest fibre content (neutral detergent fibre, NDF) in the pine forest habitat. Maximum values for fibre content go up to 70% NDF. The proportion of metabolites (ammonia, lactate, total volatile fatty acids) was highest in the Agriculture-Beech-Forest habitat (ABF). Correlations can be identified between adaptations in the microbiota and specific nutrient concentrations, as well as in strong fluctuations in ingested forage. In addition, a core bacterial community comprising five genera could be identified across all habitats, up to 44% of total relative abundance. As with all wild ruminants, many microbial genera remain largely unclassified at various taxonomic levels. This study provides a more in-depth insight into the diversity and complexity of the roe deer rumen microbiota. It highlights the key microorganisms responsible for converting naturally available nutrients of different botanical origins.

Functional traits influence patterns in vegetative and reproductive plant phenology - a multi-botanical garden study.

Phenology has emerged as key indicator of the biological impacts of climate change, yet the role of functional traits constraining variation in herbaceous species' phenology has received little attention. Botanical gardens are ideal places in which to investigate large numbers of species growing under common climate conditions. We ask whether interspecific variation in plant phenology is influenced by differences in functional traits. We recorded onset, end, duration and intensity of initial growth, leafing out, leaf senescence, flowering and fruiting for 212 species across five botanical gardens in Germany. We measured functional traits, including plant height, absolute and specific leaf area, leaf dry matter content, leaf carbon and nitrogen content and seed mass and accounted for species' relatedness. Closely related species showed greater similarities in timing of phenological events than expected by chance, but species' traits had a high degree of explanatory power, pointing to paramount importance of species' life-history strategies. Taller plants showed later timing of initial growth, and flowered, fruited and underwent leaf senescence later. Large-leaved species had shorter flowering and fruiting durations. Taller, large-leaved species differ in their phenology and are more competitive than smaller, small-leaved species. We assume climate warming will change plant communities' competitive hierarchies with consequences for biodiversity.

Adhesive luting of orthodontic devices to silica-based ceramic crowns-comparison of shear bond strength and surface properties.

OBJECTIVES: The aim of this study was to analyse the impact of different clinical conditioning approaches and an ammonium polyfluoride- and trimethoxysilylpropyl methacrylate-based experimental primer for intraoral luting of buccal tubes on silica-based ceramic surfaces. MATERIALS AND METHODS: A total of 60 leucite-reinforced glass ceramic molar crowns were conditioned using different methods (n = 10): I-roughening, hydrofluoric acid, silane; II-roughening, silane; III-roughening, experimental coupling agent; IV-experimental coupling agent; V-roughening; VI-no treatment. A buccal tube was adhesively luted to the ceramic surface. Subsequently, water storage, thermocycling and chewing simulation were carried out. The shear bond strength (SBS) was determined, and changes in the surface were assessed. RESULTS: All tubes of the control group (group VI) debonded after incubation. The conditioning methods using coupling agents revealed mean values for SBS of 61.56 MPa (group I), 45.53 MPa (group III), 41.65 MPa (group II), and 23.14 MPa (group IV). In groups I-III, both composite residues and cracks/tear-outs were detected. CONCLUSIONS: The conditioning of silicate ceramic surfaces with a suitable coupling agent system appears to allow sufficient adhesive luting of buccal tubes. The intraoral luting of fixed appliance elements on silicate ceramic surfaces using an ammonium polyfluoride- and trimethoxysilylpropyl methacrylate-based ceramic primer can withstand orthodontic forces. CLINICAL RELEVANCE: Ammonium polyfluoride- and trimethoxysilylpropyl methacrylate-based ceramic primers revealed promising results for the intraoral adhesive luting of orthodontic devices to silica-based ceramic crowns.

Annular remodelling predicts outcome in isolated severe tricuspid regurgitation: a registry-based echocardiographic analysis.

AIMS: Depending on volume status, secondary tricuspid regurgitation (sTR) has a strong dynamic component. In contrast, associated structural dilatation of the tricuspid annulus and the right heart chambers may be less volume dependent. This study aimed to assess the prognostic value of right heart remodelling in isolated severe sTR (isoTR). METHODS AND RESULTS: A total of 36 000 patients from the longitudinal echocardiographic database of our tertiary centre were screened for severe isoTR [vena contracta (VC) ≥ 7 mm] in the absence of atrial fibrillation (AF), other valve disease, and/or reduced systolic left ventricular function. Echocardiographic examinations were re-read, focusing on right ventricular (RV) parameters and on quantitative and qualitative parameters of isoTR. All-cause mortality was defined as the primary endpoint. Two hundred and sixteen patients fulfilled the inclusion criteria. Severe TR was predominant; only few were classified in the new grades massive [n = 23 (10%)] and torrential TR [n = 4 (2%)]. During a median follow-up of 35 months (20-53), all-cause mortality was 31% (n = 67). Multivariate Cox regression analysis revealed no association of VC, effective regurgitant orifice area, or regurgitant volume with all-cause mortality. However, indexed RV end-diastolic diameter (P < 0.001), indexed right atrial dimensions (P = 0.019), and particularly tricuspid valve (TV) annulus diameter diastole index (P = 0.002) and TV annulus diameter systole index (P = 0.001) were significantly associated with outcome. CONCLUSION: Severe isolated TR in the absence of AF is a rare finding with a grim prognosis. Tricuspid annular diameter dimensions rather than quantitative measures of TR proved to be of significant prognostic value indicating a continuous remodelling leading to a 'point of no return' with a dismal outcome.

Phthalocyanine dimers in a blend: spectroscopic and theoretical studies of MnPc(δ +)/F(16)CoPc(δ -).

We have prepared mixed phthalocyanine films out of MnPc and F(16)CoPc, which were characterized by means of photoemission spectroscopy and electron energy-loss spectroscopy. Our data reveal the formation of MnPc/F(16)CoPc charge transfer dimers in analogy to the related heterojunction. The electronic excitation spectrum of these blends is characterized by a new low energy excitation at 0.6 eV. Density functional theory calculations show that the new signal is caused by a strong absorption between the states of the interface induced two level system.

"Get the best out of what comes in" - adaptation of the microbiota of chamois (Rupicapra rupicapra) to seasonal forage availability in the Bavarian Alps.

As an inhabitant of the Alps, chamois are exposed to significant climatic changes throughout the year and are also strongly confronted with changing forage availability. Besides horizontal and vertical migratory movements as an adaptation, it undergoes physiological transformations and dynamic changes in the ruminal microbiota. The following study used 48 chamois of different ages and genders to investigate to which extent the ingested food plants, the resulting crude nutrients in the rumen (reticulorumen) contents, and the bacterial microbiota in the rumen and their fermentation products were influenced by the changes over the seasons. Very little is known about the microbiota of wild ruminants, and many bacterial taxa could only be determined to certain taxonomic levels in this study. However, adapted microbiota reflects the significant changes in the ingested forage and the resulting crude nutrients. For some taxa, our results indicated potential functional relationships. In addition, 15 genera were identified, representing almost 90% of the relative abundance, forming the central part of the microbial community throughout the year. The successful and flexible adaptation of chamois is reflected in the chamois rumen's nutrient and microbial profile. This is also the first study that analyzes the microbiota of the chamois using rumen samples and considers the microbiota in a seasonal comparison.

Spatial scaling in bed-site selection by roe deer fawns: Implications for mitigating neonatal mortality during mowing.

When habitat use by field-dwelling animals coincides in space and time with agricultural practices such as spring mowing of meadows, human-wildlife conflicts can have deadly consequences for wildlife. Roe deer (Capreolus capreolus L.) fawns are particularly vulnerable because they hide in meadows during the rearing phase. Thus, a better understanding of the habitat drivers of bed-site selection is critical to mitigating fawn mortality during mowing. Here, we tease apart the among-field (presumably driven by maternal behaviour) and within-field (driven by fawn behaviour) components of bed-site selection of roe deer during the spring mowing season. We collected over 600 fawn bed sites across an environmentally diverse study region. At the among-field scale, we implemented a used versus available design and employed a two-part statistical model (GAMLSS) to identify habitat characteristics that were linked to either fawn presence (vs. absence) or abundance on a given field. At the within-field scale, we compared habitat characteristics at fawn bed-sites with paired random sites using a conditional logistic regression model. At the among-field scale, fawns were more likely to be present, and were more abundant, in fields within more diverse, rural landscapes, with nearby woodland. Surprisingly, fawns were more often present in fields that were near roads and had lower vegetation productivity. At the within-field scale, however, fawns preferred bed-sites which were further from both roads and woodland, but that provided the best visual cover to minimise predation risk. Our findings revealed substantial and novel scale-dependent differences in the drivers of habitat selection of mothers and fawns, which, together, determine the precise locations of bed-sites between and within meadows. These results may aid wildlife managers in identifying areas where there is a high probability of encountering a roe deer fawn so as to initiate targeted searches prior to mowing and, ultimately, mitigate fawn mowing mortality.

Momentum dependence of the excitons in pentacene.

We have carried out electron energy-loss investigations of the lowest singlet excitons in pentacene at 20 K. Our studies allow to determine the full exciton band structure in the a∗, b∗ reciprocal lattice plane. The lowest singlet exciton can move coherently within this plane, and the resulting exciton dispersion is highly anisotropic. The analysis of the energetically following (satellite) features indicates a strong admixture of charge transfer excitations to the exciton wave function.

CD34+CD140b+ cells and circulating CXCL12 correlate with the angiographically assessed severity of cardiac allograft vasculopathy.

AIMS: We sought to determine whether circulating vascular progenitor cells, such as endothelial progenitor cells (EPCs) or smooth muscle progenitor cells (SPCs), were associated with the severity of cardiac allograft vasculopathy (CAV). METHODS AND RESULTS: CD34(+)CD140b(+) SPCs and CD34(+)KDR(+) EPCs were measured in the peripheral circulation of 187 adult heart transplant recipients by flow cytometry. Cardiac allograft vasculopathy was quantified by angiography using a CAV-specific scoring system. Cardiac allograft vasculopathy was present in 84 patients (44.7%) and was classified as mild in 59 and severe in 25 cases. Circulating SPCs were more frequently detectable in CAV patients than in patients without CAV. The number of CD34(+)CD140b(+) cells showed a stepwise increase in patients with moderate and severe CAV. Smooth muscle progenitor cell counts were higher in patients with coronary stent implant compared with unstented patients with CAV. In contrast, peripheral CD34(+)KDR(+) EPC counts were not changed in CAV patients. Plasma CXCL12 levels correlated with the degree of CAV and SPC counts. None of the different immunosuppressive drug regimes was related to the SPC count or the CXCL12 levels. A multivariate regression analysis revealed that the SPC count was independently associated with the presence of CAV. CONCLUSION: Circulating SPCs, but not EPCs, and plasma CXCL12 concentrations are elevated in CAV patients, indicating that they play prominent roles in transplant arteriosclerosis.

Acid resistance of self-adhesive resin luting cements - changes in surface texture parameters and microhardness.

OBJECTIVES: When consumed in excess, acidic foods and beverages can cause dental erosions leading to irreversible loss of tooth substance. In many cases, prosthetic rehabilitation of the damaged teeth is mandatory. The aim of this in vitro study was to investigate, for the first time on this scale, the resistance of various commonly used self-adhesive resin luting cements (Bifix SE, VOCO; G-Cem LinkAce, GC; RelyX Unicem, 3 M Oral Care; SpeedCEM Plus, Ivoclar ) against acidic media, and to find out whether they can withstand long-term exposure. These results were compared with an adhesive resin luting cement (Panavia V5, Kuraray) that functioned as reference gold standard. Furthermore we applied area roughness parameters for surface texture analysis in the present investigation, to highlight their advantages for investigations on the surface quality of resin luting cements. METHODS: Six specimens with identical diameter (10 mm) and thickness (3 mm) were prepared from each self-adhesive and adhesive resin luting cement and forwarded to an incubation in various acidic media for a period of 232 h. Conductivity and pH-values of each acidic medium was analyzed for each material group prior (t 0) and after exposure (t 1). The specimens were examined for Vickers microhardness and surface quality. For the evaluation of surface roughness, the parameters Sa, Sdr, Spc Spk, Sk, and Svk were investigated by using different filtered surfaces (S-L; S-F) according to ISO 25 178. Statistical analysis was conducted at a significance level of α = 0.050. RESULTS: For the evaluation of the acid resistance of self-adhesive resin luting cements investigations on conductivity and pH-value assessment of storage solution appear unsuitable, while the assessment of microhardness and surface analysis revealed valid data. It could be shown that changes in surface texture of the resin luting cements can be determinend in qualitative and quantitative manner. While the microhardness and surface quality of some resin luting cements hardly changed, others showed significantly reduced values in microhardness and changes in their surface quality (p < 0.001). SIGNIFICANCE: The data of the current study emphasize the relevance of interactions between resin luting cements and acids and suggest further laboratory and clinical studies to elucidate its impact on the clinical performance of the materials investigated.

TEGDMA-Functionalized Dicalcium Phosphate Dihydrate Resin-Based Composites Prevent Secondary Caries in an In Vitro Biofilm Model.

This study evaluated the efficacy of experimental TEGDMA-functionalized dicalcium phosphate dihydrate (T-DCPD) filler-based resin-based composites (RBC) in preventing caries lesions around the restoration margins (secondary caries, SC). Standardized Class-II cavities were made in sound molars with the cervical margin in dentin. Cavities were filled with a commercial resin-modified glass-ionomer cement (RMGIC) or experimental RBCs containing a bisGMA-TEGDMA resin blend and one of the following inorganic fractions: 60 wt.% Ba glass (RBC-0); 40 wt.% Ba glass and 20 wt.% T-DCPD (RBC-20); or 20 wt.% Ba glass and 40 wt.% T-DCPD (RBC-40). An open-system bioreactor produced Streptococcus mutans biofilm-driven SC. Specimens were scanned using micro-CT to evaluate demineralization depths. Scanning electron microscopy and energy-dispersive X-ray spectroscopy characterized the specimen surfaces, and antimicrobial activity, buffering effect, and ion uptake by the biofilms were also evaluated. ANOVA and Tukey's tests were applied at p < 0.05. RBC-0 and RBC-20 showed SC development in dentin, while RBC-40 and RMGIC significantly reduced the lesion depth at the restoration margin (p < 0.0001). Initial enamel demineralization could be observed only around the RBC-0 and RBC-20 restorations. Direct antibiofilm activity can explain SC reduction by RMGIC, whereas a buffering effect on the acidogenicity of biofilm can explain the behavior of RBC-40. Experimental RBC with CaP-releasing functionalized T-DCPD filler could prevent SC with the same efficacy as F-releasing materials.

Severe tricuspid regurgitation: prognostic role of right heart remodelling and pulmonary hypertension.

AIMS: Left heart diseases (LHDs) are the main driving forces for the development of functional tricuspid regurgitation (TR). Therefore, in most cases, the true prognostic value of TR remains concealed by concomitant LHD. This study aimed to analyse right heart remodelling in patients with TR without other valve disease and with normal systolic left ventricular function (sysLVF), and to stratify its prognostic value in the presence (dPH, maximal TR velocity signal (TRVmax) ≥ 3.5 m/s in echocardiography) or absence (nsPH, TRVmax < 3.5m/s) of concomitant pulmonary hypertension (PH). METHODS AND RESULTS: We performed an observational analysis of all patients diagnosed with TR in the absence of other valve disease and reduced sysLVF at our institution between 1 January 2003 and 31 December 2013. Five-year mortality was chosen as endpoint. The final cohort entailed 29 979 consecutive patients (median age 60 years, interquartile range 46-70), 49.9% were male, mean follow-up was 95±49 months. Severe TR was present in 790 patients (2.6%). In dPH and in nsPH, severe TR was associated with an excess 5-year mortality that was even more pronounced in the dPH group (58.2% vs. 43.6%, P = 0.001). In nsPH, right ventricular dysfunction predicted mortality. In dPH, mortality was independent of presence or absence of right heart dilatation or dysfunction. CONCLUSION: Severe TR without concomitant left heart valve disease or LV systolic dysfunction was a rare disease in this large-scale all-comer population and is associated with an unfavourable prognosis. The differentiation of patients with nsPH and dPH is essential as they present with different patterns of right heart remodelling and with different long-time outcomes.

A radical procedure for the anti-Markovnikov hydroazidation of alkenes.

A one-pot procedure for the efficient hydroazidation of alkenes involving hydroboration with catecholborane followed by reaction with benzenesulfonyl azide in the presence of a radical initiator is described. The regioselectivity is controlled by the hydroboration step and corresponds in most cases to an anti-Markovnikov regioselectivity. This procedure is applicable to a wide range of alkenes and gives excellent results with 1,2-disubstituted and trisubstituted alkenes.

Effect of charge order on the plasmon dispersion in transition-metal dichalcogenides.

We investigate the dispersion of the charge carrier plasmon in the three prototypical charge-density wave bearing transition-metal dichalcogenides 2H-TaSe(2), 2H-TaS(2), and 2H-NbSe(2) employing electron energy-loss spectroscopy. For all three compounds the plasmon dispersion is found to be negative for small momentum transfers. This is in contrast with the generic behavior observed in simple metals as well as the related system 2H-NbS(2), which does not exhibit charge order. We present a semiclassical Ginzburg-Landau model which accounts for these observations, and argue that the vicinity to a charge ordered state is thus reflected in the properties of the collective excitations.

Do systemic risk factors impact invasive findings from virtual histology? Insights from the international virtual histology registry.

AIMS: Cardiovascular risk factors such as elevated serum lipid levels are important in the development of coronary atherosclerosis. Radiofrequency (RF) analysis of intravascular ultrasound [IVUS, Virtual histology (VH)] offers a unique tool to study the composition of coronary atherosclerotic plaque in vivo. We used data from the multicentre VH registry to assess the association between cardiovascular risk factors and coronary plaque volume and composition. METHODS AND RESULTS: Between August 2004 and July 2006, 990 patients in 42 centres were enrolled in a prospective, multicentre, non-randomized global VH registry. Coronary artery imaging was performed by conventional IVUS and RF-IVUS. The four RF-IVUS plaque components [dense calcium (DC), necrotic core (NC), fibrous (F) tissue, and fibro fatty (FF)] were analysed in every recorded frame. The results were expressed as mean cross-sectional areas, absolute volume, and percentage of total plaque volume. Risk factor assessment included evaluation of family history of previous myocardial infarction (MI), past or current smoking, diabetes mellitus, hypertension, and the laboratory measurements. Patients with diabetes had an increased relative proportion of NC (6.47 +/- 0.28 vs. 5.86 +/- 0.14%, P = 0.037) and DC (4.58 +/- 0.27 vs. 3.90 +/- 0.14%, P = 0.017), and patients with hypertension had an increased relative proportion of FF, DC (4.35 +/- 0.16 vs. 3.57 +/- 0.17%, P = 0.02) and NC (6.24 +/- 0.17 vs. 5.60 +/- 0.19%, P = 0.01). Compared with patients with LDL-C <100 mg/dL, patients with LDL-C >160 mg/dL had higher plaque volume (342.1 +/- 26.2 vs. 318.6 +/- 10.7 mm(3)). Linear regression analysis showed a correlation between the level of HDL-C and F (r = -0.149, P < 0.01), FF (r = -0.106, P < 0.01), and NC (r = -0.90, P < 0.05). The level of LDL correlated with F (r = 0.110, P < 0.01). Patients with prior MI have an increased percentage of F (30.03 +/- 0.59 vs. 28.20 +/- 0.37%, P = 0.009). Smoking had no relevant effect on plaque composition. Treatment with acetylsalicylacid and statins reduced FF with altering plaque volume. CONCLUSION: Radiofrequency-IVUS detects marked differences in coronary plaque composition related to the risk factor profile with particular focus on lipid levels. Greater amounts of NC were associated with diabetes, hypertension, MI, and low HDL-C. The effects of treatment of changes related to plaque composition are underway.

Prognostic Value of Echocardiographic Right Ventricular Function Parameters in the Presence of Severe Tricuspid Regurgitation.

BACKGROUND: Presence of severe tricuspid regurgitation (TR) has a significant impact on assessment of right ventricular function (RVF) in transthoracic echocardiography (TTE). High trans-valvular pendulous volume leads to backward-unloading of the right ventricle. Consequently, established cut-offs for normal systolic performance may overestimate true systolic RVF. METHODS: A retrospective analysis was performed entailing all patients who underwent TTE at our institution between 1 January 2013 and 31 December 2016. Only patients with normal left ventricular systolic function and with no other valvular lesion were included. All recorded loops were re-read by one experienced examiner. Patients without severe TR (defined as vena contracta width ≥7 mm) were excluded. All-cause 2-year mortality was chosen as the end-point. The prognostic value of several RVF parameters was tested. RESULTS: The final cohort consisted of 220 patients, 88/220 (40%) were male. Median age was 69 years (IQR 52-79), all-cause two-year mortality was 29%, median TAPSE was 19 mm (15-22) and median FAC was 42% (30-52). In multivariate analysis, TAPSE with the cutoff 17 mm and FAC with the cutoff 35% revealed non-significant hazard ratios (HR) of 0.75 (95%CI 0.396-1.421, p = 0.38) and 0.845 (95%CI 0.383-1.867, p = 0.68), respectively. TAPSE with the cutoff 19 mm and visual eyeballing significantly predicted survival with HRs of 0.512 (95%CI 0.296-0.886, p = 0.017) and 1.631 (95%CI 1.101-2.416, p = 0.015), respectively. CONCLUSIONS: This large-scale all-comer study confirms that RVF is one of the main drivers of mortality in patients with severe isolated TR. However, the current cut-offs for established echocardiographic parameters did not predict survival. Further studies should investigate the prognostic value of higher thresholds for RVF parameters in these patients.

A machine learning algorithm supports ultrasound-naïve novices in the acquisition of diagnostic echocardiography loops and provides accurate estimation of LVEF.

Left ventricular ejection fraction (LVEF) is the most important parameter in the assessment of cardiac function. A machine-learning algorithm was trained to guide ultrasound-novices to acquire diagnostic echocardiography images. The artificial intelligence (AI) algorithm then estimates LVEF from the captured apical-4-chamber (AP4), apical-2-chamber (AP2), and parasternal-long-axis (PLAX) loops. We sought to test this algorithm by having first-year medical students without previous ultrasound knowledge scan real patients. Nineteen echo-naïve first-year medical students were trained in the basics of echocardiography by a 2.5 h online video tutorial. Each student then scanned three patients with the help of the AI. Image quality was graded according to the American College of Emergency Physicians scale. If rated as diagnostic quality, the AI calculated LVEF from the acquired loops (monoplane and also a "best-LVEF" considering all views acquired in the particular patient). These LVEF calculations were compared to images of the same patients captured and read by three experts (ground-truth LVEF [GT-EF]). The novices acquired diagnostic-quality images in 33/57 (58%), 49/57 (86%), and 39/57 (68%) patients in the PLAX, AP4, and AP2, respectively. At least one of the three views was obtained in 91% of the attempts. We found an excellent agreement between the machine's LVEF calculations from images acquired by the novices with the GT-EF (bias of 3.5% ± 5.6 and r = 0.92, p < 0.001 in the "best-LVEF" algorithm). This pilot study shows first evidence that a machine-learning algorithm can guide ultrasound-novices to acquire diagnostic echo loops and provide an automated LVEF calculation that is in agreement with a human expert.

A novel class of nitrovasodilators: potency and in vitro tolerance of organic aminoalkylnitrates.

Experimental studies on organic alkylnitrates have shown that both vasodilator potency and development of in vitro tolerance (tachyphylaxis) correlate with the number of nitrate groups in the molecule. However, introduction of an amino group to ethylnitrate yielded 2-nitrooxyethylammoniumnitrate (1), which is highly active but without inducing in vitro tolerance. Therefore, we prepared a series of aminoalkylnitrates and investigated vasorelaxation and tachyphylaxis on isolated prostaglandin F2alpha-precontracted porcine pulmonary arteries with intact endothelium. Tachyphylaxis was studied by incubating the arteries with EC100 of the respective aminoalkylnitrate and, after a 45-minute washout phase, measuring vasorelaxation again. All of the aminoalkylnitrates caused vasodilation, but the effect did not correlate with the number of nitrate moieties in the molecule. None of the substances was able to outperform compound 1, not even oligonitrates. Generally, structure­activity relationships found for alkylnitrates are obviously not valid for aminoalkylnitrates. Whereas the most potent aminomononitrate 1 evokes no in vitro tolerance, others exhibit tachyphylaxis independently of their vasodilator potency. We have shown that vasorelaxant activity and induction of tachyphylaxis are modulated significantly by introduction of an amino group to the alkylnitrate scaffold. Our results indicate that aminoalkylnitrates have to be considered as an individual class of nitrovasodilators with different structure­activity relationships and vasodilator properties.