The Importance Of Monoclonal Proteins Determination For The Correct Diagnosis Of Transthyretin Cardiac Amyloidosis By [Tc-99m]Tc-diphosphonates

EPS-066 Aim/Introduction: To analyze the influence of the determination of free monoclonal proteins in blood and urine in the final diagnosis of Transthyretin Cardiac Amyloidosis (TTRA). Materials and Methods: We have analyzed 200 [99mTc]Tc-diphosphonates scans: 192 performed on 190 patients under suspicion of TTRA and 7 patients with grade II-III radiotracer myocardial deposit as a casual finding (November/2013 - January/2020). Likewise, clinical and laboratory characteristics (heart failure, LVEF, proBNP levels, immunofixation in serum and/or urine for the detection of monoclonal chains and chronic renal failure) have been evaluated. A positive case has been considered for TTRAwt or senile (Score Perugini II-III scan, negative immunofixation in serum and/or urine, negative genetic study), positive case for hereditary TTRA (Score Perugini II-III scan, negative immunofixation and positive genetic study), positive case for secondary amyloidosis (positive immunofixation and presence of hematologic malignancy) and undetermined amyloidosis (immunofixation not performed or positive and absence of haematologic malignancies at follow-up). Results: 59 positive scans have been detected, 47 men (79’7%) and 12 women (20’3%). The mean age of the group of positives was 82’66 years, while that of the negatives was 72’15. The mean proBNP levels in the positives are 7561, compared to 5869 in the negative group. Immunofixation (serum and/or urine for detection of kappa or lambda monoclonal chains at 30 (50.8%) has been performed on these patients. Finally, 37.2% (22/59) resulted in ATTRwt, 3.4% (2/59) hereditary ATTR (genetic study: variant E54Q and mutation c.424> A (p.Va.122Ile) in exon 4 of TTR) and 1.7% (1/59) secondary amyloidosis. The remaining 34/59 (57.7%) cases were undetermined amyloidosis (6 positive immunofixation and 27 without monoclonal proteins determination). Conclusion: Determination of monoclonal bands in blood and urine is mandatory to correctly characterize cases of cardiac amyloidosis and, in presence of monoclonal bands, to assess the existence of underlying haematological malignancies

Impact Of Sentinel Lymph Node Biopsy In Breast Cancer Patients Treated With Neoadjuvant Chemotherapy

EPS 196 Aim/Introduction: To analyze how many of the patients undergoing neoadjuvant chemotherapy (NCT) may benefit from SLNB, as well as the impact on patient management, especially in those with early axillary involvement. Materials and Methods: We included patients with breast carcinoma candidates to NCT discussed at the Tumor Committee of our hospital (April/2017-August/2019). All of them were subjected to clinical assessment, ultrasound and, if appropriate, histological analysis, axillary pre and post- NCT. Sentinel lymph node detection was performed after periareolar injection of [99mTc]Tc-nanocoloid (74 MBq) the day before surgery. In some cases, blue dye was injected and/or a pre-NPC metal clip was placed in the affected node. Results: Sixty-two patients were included. NCT achieved a complete breast response in 12 patients, partial in 46 and non-response in 4. Initially, 31 patients were classified as N0 and 31 as N+ (28 N1 and 3 N2), achieving a complete axillary response in 58% of N+ (18). SLNB was performed in 49 patients (79%; 100% in N0 and 58% in N+ from baseline). The gamma detection rate of the sentinel lymph node was 91.8% (93.5% in N0 and 88.9% in N+). 28 lymphadenectomies were undergone (45.2%; 22.5% in N0 and 67.7% in N+), 11 due to positive SLNB (5 N0 and 6 N1), 13 owing to lack of axillary response and 4 caused by the non-localization of the sentinel lymph node. SLNB was performed in 58% of N+ patients, of which 44.4% were negative, avoiding lymphadenectomy. Metal clip and/or blue dye techniques were used in 31 cases (50%). Conclusion: SLNB is viable in a high percentage of patients with previous NCT, with a high detection rate, even in patients with early affected axilla, avoiding lymphadenectomy to patients who achieve a complete response of the axillary lymph node

Substituent and ring effects on enthalpies of formation: 2-methyl- and 2-ethylbenzimidazoles versus benzene-and imidazole-derivatives

The enthalpies of combustion, heat capacities, enthalpies of sublimation and enthalpies of formation of 2-methylbenzimidazole (2MeBIM) and 2-ethylbenzimidazole (2EtBIM) are reported and the results compared with those of benzimidazole itself (BIM). Theoretical estimates of the enthalpies of formation were obtained through the use of atom equivalent schemes. The necessary energies were obtained in single-point calculations at the B3LYP/6-311+G(d,p) on B3LYP/6-31G* optimized geometries. The comparison of experimental and calculated values of benzenes, imidazoles and benzimidazoles bearing H (unsubstituted), methyl and ethyl groups shows remarkable homogeneity. The energetic group contribution transferability is not followed, but either using it or adding an empirical interaction term, it is possible to generate an enormous collection of reasonably accurate data for different substituted heterocycles (pyrazole-derivatives, pyridine-derivatives, etc.) from the large amount of values available for substituted benzenes and those of the parent (pyrazole, pyridine) heterocycles.We acknowledge the financial support of the DGI/MCyT (project nos. BQU-2003-00976, 01251 and 05827). This work has been partially supported by the DGI project no. BQU-2003-00894. A generous allocation of computational time at the CCC of the Universidad Auto´noma de Madrid is also gratefully acknowledged. Thanks are also due to Instituto de Cooperac¸a˜o Cientı´fica e Tecnolo´gica Internacional (ICCTI), Lisbon, Portugal, and Consejo Superior de Investigaciones Cientı´ficas (CSIC), Madrid, Spain, for a joint research project ICCTI/CSIC. MLPFA thanks Fundac¸a˜o para a Cieˆncia e Tecnologia (FCT), Lisbon, Portugal, for the award of a postdoctoral fellowship (PRAXIS XXI/BPD/16319/98) and MT thanks MECD/SEEU (AP 2002-0603), Spain, for financial support

Substituent effects on enthalpies of formation of nitrogen heterocycles: 2-substituted benzimidazoles and related compounds

The enthalpies of combustion, heat capacities, enthalpies of sublimation and enthalpies of formation of 2-tert-butylbenzimidazole (2tBuBIM) and 2-phenylimidazole (2PhIM) are reported and the results compared with those of benzene derivatives and a series of azoles (imidazoles, pyrazoles, benzimidazoles and indazoles). Theoretical estimates of the enthalpies of formation were obtained through the use of atom equivalent schemes. The necessary energies were obtained in single-point calculations at the B3LYP/6-311++G(d,p) on B3LYP/6-31G* optimized geometries. The comparison of experimental and calculated values of all studied compounds bearing H (unsubstituted), methyl (Me) ethyl (Et), propyl (Pr), isopropyl (iPr), tert-butyl (tBu), benzyl (Bn) and phenyl (Ph) groups show remarkable homogeneity. The remarkable consistency of both the calculated and experimental results allows us to predict with reasonable certainty the missing experimental values. The crystal and molecular structure of the 2-benzylbenzimidazole (2BnBIM) has been determined by X-ray analysis. The observed molecular conformation permits the crystal being built up through N−H···N hydrogen bonds and van der Waals contacts between the molecules. An attempt has been made to relate the crystal structure to the enthalpies of sublimation.Thanks are due to Instituto de Cooperac¸a˜o Cientı´fica e Tecnolo´gica International (ICCTI), Lisbon, Portugal, and Consejo Superior de Investigaciones Cientı´ficas (CSIC), Madrid, Spain. L.M.P.F.A. thanks Fundac¸a˜o para a Cieˆncia e Tecnologia (FCT), Lisbon, Portugal, for the award of a postdoctoral fellowship (PRAXIS XXI/BPD/16319/98). This work has also been financed by DGICYT (BQU-2003- 00894, -00976 and -01251)

Experimental thermochemical study of two 2-alkylbenzimidazole isomers (alkyl = propyl and isopropyl)

This paper reports the values of the standard (p∘=0.1 MPa) molar enthalpy of formation in the condensed, at T=298.15 K, for 2-R-benzimidazoles (R=propyl, isopropyl), derived from, the respective enthalpies of combustion in oxygen, measured by static bomb combustion calorimetry and the standard molar enthalpies of sublimation, at T=298.15 K, obtained using Calvet microcalorimetry in the case of 2-isopropylbenzimidazole and, by the variation of vapour pressures, determined by the Knudsen effusion technique, with temperatures between (344 and 365) K for 2-propylbenzimidazole. Heat capacities, in the temperature ranges from T=268 K to near their respective melting temperatures, T=421 K for 2-propylbenzimidazole and T=464 K for 2-isopropylbenzimidazole, were measured with a differential scanning calorimeter. These values were used to derive the standard molar enthalpies of formation, of the two 2-benzimidazole derivatives, in gaseous phase.Thanks are due to Instituto de Cooperação Cientı́fica e Tecnológica Industrial (ICCTI), Lisbon, Portugal, and Consejo Superior de Investigaciones Cientı́ficas (CSIC), Madrid, Spain for a joint research project CSIC/ICCTI; M.L.P.F.A. thanks Fundação para a Ciência e Tecnologia (FCT), Lisbon, Portugal, for the award of a postdoctoral fellowship (SRFH/BPD/5595/2001). The Spanish DGI/MCyT is acknowledged under projects BQU2000-0252, 0906 and 1497; M.T. thanks MECD/SEEU, AP2002-0603, Spain for financial support

Atmospheric Ice‐Nucleating Particles in the Dusty Tropical Atlantic

Desert dust is one of the most important atmospheric ice-nucleating aerosol species around the globe. However, there have been very few measurements of ice-nucleating particle (INP) concentrations in dusty air close to desert sources. In this study we report the concentration of INPs in dust laden air over the tropical Atlantic within a few days' transport of one of the world's most important atmospheric sources of desert dust, the Sahara. These measurements were performed as part of the Ice in Clouds Experiment-Dust campaign based in Cape Verde, during August 2015. INP concentrations active in the immersion mode, determined using a droplet-on-filter technique, ranged from around 10² m⁻³ at -12°C to around 10⁵ m⁻³ at -23°C. There is about 2 orders of magnitude variability in INP concentration for a particular temperature, which is determined largely by the variability in atmospheric dust loading. These measurements were made at altitudes from 30 to 3,500 m in air containing a range of dust loadings. The ice active site density (n s ) for desert dust dominated aerosol derived from our measurements agrees with several laboratory-based parameterizations for ice nucleation by desert dust within 1 to 2 orders of magnitude. The small variability in n s values determined from our measurements (within about 1 order of magnitude) is striking given that the back trajectory analysis suggests that the sources of dust were geographically diverse. This is consistent with previous work, which indicates that desert dust's ice-nucleating activity is only weakly dependent on source

Ice-nucleating ability of aerosol particles and possible sources at three coastal marine sites

Despite the importance of ice-nucleating particles (INPs) for climate and precipitation, our understanding of these particles is far from complete. Here, we investigated INPs at three coastal marine sites in Canada, two at mid-latitude (Amphitrite Point and Labrador Sea) and one in the Arctic (Lancaster Sound). For Amphitrite Point, 23 sets of samples were analyzed, and for Labrador Sea and Lancaster Sound, one set of samples was analyzed for each location. At all three sites, the ice-nucleating ability on a per number basis (expressed as the fraction of aerosol particles acting as an INP) was strongly dependent on the particle size. For example, at diameters of around 0.2µm, approximately 1 in 106 particles acted as an INP at −25°C, while at diameters of around 8µm, approximately 1 in 10 particles acted as an INP at −25°C. The ice-nucleating ability on a per surface-area basis (expressed as the surface active site density, ns) was also dependent on the particle size, with larger particles being more efficient at nucleating ice. The ns values of supermicron particles at Amphitrite Point and Labrador Sea were larger than previously measured ns values of sea spray aerosols, suggesting that sea spray aerosols were not a major contributor to the supermicron INP population at these two sites. Consistent with this observation, a global model of INP concentrations under-predicted the INP concentrations when assuming only marine organics as INPs. On the other hand, assuming only K-feldspar as INPs, the same model was able to reproduce the measurements at a freezing temperature of −25°C, but under-predicted INP concentrations at −15°C, suggesting that the model is missing a source of INPs active at a freezing temperature of −15°C

Not all feldspars are equal: a survey of ice nucleating properties across the feldspar group of minerals

Mineral dust particles from wind-blown soils are known to act as effective ice nucleating particles in the atmosphere and are thought to play an important role in the glaciation of mixed phase clouds. Recent work suggests that feldspars are the most efficient nucleators of the minerals commonly present in atmospheric mineral dust. However, the feldspar group of minerals is complex, encompassing a range of chemical compositions and crystal structures. To further investigate the ice-nucleating properties of the feldspar group we measured the ice nucleation activities of 15 characterized feldspar samples. We show that alkali feldspars, in particular the potassium feldspars, generally nucleate ice more efficiently than feldspars in the plagioclase series which contain significant amounts of calcium. We also find that there is variability in ice nucleating ability within these groups. While five out of six potassium-rich feldspars have a similar ice nucleating ability, one potassium rich feldspar sample and one sodium-rich feldspar sample were significantly more active. The hyper-active Na-feldspar was found to lose activity with time suspended in water with a decrease in mean freezing temperature of about 16°C over 16 months; the mean freezing temperature of the hyper-active K-feldspar decreased by 2°C over 16 months, whereas the "standard" K-feldspar did not change activity within the uncertainty of the experiment. These results, in combination with a review of the available literature data, are consistent with the previous findings that potassium feldspars are important components of arid or fertile soil dusts for ice nucleation. However, we also show that there is the possibility that some alkali feldspars may have enhanced ice nucleating abilities, which could have implications for prediction of ice nucleating particle concentrations in the atmosphere

The first multi-model ensemble of regional climate simulations at kilometer-scale resolution, part I: evaluation of precipitation

Here we present the first multi-model ensemble of regional climate simulations at kilometer-scale horizontal grid spacing over a decade long period. A total of 23 simulations run with a horizontal grid spacing of ∼3 km, driven by ERA-Interim reanalysis, and performed by 22 European research groups are analysed. Six different regional climate models (RCMs) are represented in the ensemble. The simulations are compared against available high-resolution precipitation observations and coarse resolution (∼ 12 km) RCMs with parameterized convection. The model simulations and observations are compared with respect to mean precipitation, precipitation intensity and frequency, and heavy precipitation on daily and hourly timescales in different seasons. The results show that kilometer-scale models produce a more realistic representation of precipitation than the coarse resolution RCMs. The most significant improvements are found for heavy precipitation and precipitation frequency on both daily and hourly time scales in the summer season. In general, kilometer-scale models tend to produce more intense precipitation and reduced wet-hour frequency compared to coarse resolution models. On average, the multi-model mean shows a reduction of bias from ∼ −40% at 12 km to ∼ −3% at 3 km for heavy hourly precipitation in summer. Furthermore, the uncertainty ranges i.e. the variability between the models for wet hour frequency is reduced by half with the use of kilometer-scale models. Although differences between the model simulations at the kilometer-scale and observations still exist, it is evident that these simulations are superior to the coarse-resolution RCM simulations in the representing precipitation in the present-day climate, and thus offer a promising way forward for investigations of climate and climate change at local to regional scales

Testing Multiple Coordination Constraints with a Novel Bimanual Visuomotor Task

The acquisition of a new bimanual skill depends on several motor coordination constraints. To date, coordination constraints have often been tested relatively independently of one another, particularly with respect to isofrequency and multifrequency rhythms. Here, we used a new paradigm to test the interaction of multiple coordination constraints. Coordination constraints that were tested included temporal complexity, directionality, muscle grouping, and hand dominance. Twenty-two healthy young adults performed a bimanual dial rotation task that required left and right hand coordination to track a moving target on a computer monitor. Two groups were compared, either with or without four days of practice with augmented visual feedback. Four directional patterns were tested such that both hands moved either rightward (clockwise), leftward (counterclockwise), inward or outward relative to each other. Seven frequency ratios (3∶1, 2∶1, 3∶2, 1∶1, 2∶3. 1∶2, 1∶3) between the left and right hand were introduced. As expected, isofrequency patterns (1∶1) were performed more successfully than multifrequency patterns (non 1∶1). In addition, performance was more accurate when participants were required to move faster with the dominant right hand (1∶3, 1∶2 and 2∶3) than with the non-dominant left hand (3∶1, 2∶1, 3∶2). Interestingly, performance deteriorated as the relative angular velocity between the two hands increased, regardless of whether the required frequency ratio was an integer or non-integer. This contrasted with previous finger tapping research where the integer ratios generally led to less error than the non-integer ratios. We suggest that this is due to the different movement topologies that are required of each paradigm. Overall, we found that this visuomotor task was useful for testing the interaction of multiple coordination constraints as well as the release from these constraints with practice in the presence of augmented visual feedback