We have demonstrated that myocardial acceleration during isovolumic contraction (IVA) is a sensitive index of right ventricular contractile function. In this study, we assessed the usefulness of IVA ...to measure left ventricular (LV) contractile function and force-frequency relationships in an experimental preparation.
In study 1, we examined 6 pigs by use of tissue Doppler imaging of LV free wall and simultaneous measurements of intraventricular pressure, volume, maximal elastance (Emax), and dP/dtmax by conductance catheterization. Animals were paced via the right atrium at a rate of 130 bpm. IVA was compared with elastance during contractility modulation by esmolol and dobutamine and assessed during preload reduction and afterload increase. In study 2, in 6 more pigs, force-frequency data were obtained during incremental atrial pacing from 120 to 180 bpm. Study 1: Esmolol led to a decrease in IVA and Emax (P<0.03 and <0.02, respectively), both of which increased during dobutamine infusion (P<0.02 and <0.03, respectively). IVA was unaffected by significant (P<0.001) acute reduction of LV volume and a significantly increased LV afterload (systolic pressure increase, P<0.001). Study 2: There was a positive correlation between IVA and dP/dtmax (r2=0.92, P<0.05). As heart rate was increased from 120 to 160 bpm, there were significant increases in both IVA and dP/dtmax (P<0.0004 and P=0.02, respectively). Over the same range of heart rates, there was no significant change in Emax (P=0.22).
IVA is a measurement of LV contractile function that is unaffected by preload and afterload changes within a physiological range and can be used noninvasively to measure LV force-frequency relationships.
Determining the architecture of multi-planetary systems is one of the cornerstones of understanding planet formation and evolution. Resonant systems are especially important as the fragility of their ...orbital configuration ensures that no significant scattering or collisional event has taken place since the earliest formation phase when the parent protoplanetary disc was still present. In this context, TOI-178 has been the subject of particular attention since the first TESS observations hinted at the possible presence of a near 2:3:3 resonant chain. Here we report the results of observations from CHEOPS, ESPRESSO, NGTS, and SPECULOOS with the aim of deciphering the peculiar orbital architecture of the system. We show that TOI-178 harbours at least six planets in the super-Earth to mini-Neptune regimes, with radii ranging from 1.152
−0.070
+0.073
to 2.87
−0.13
+0.14
Earth radii and periods of 1.91, 3.24, 6.56, 9.96, 15.23, and 20.71 days. All planets but the innermost one form a 2:4:6:9:12 chain of Laplace resonances, and the planetary densities show important variations from planet to planet, jumping from 1.02
−0.23
+0.28
to 0.177
−0.061
+0.055
times the Earth’s density between planets
c
and
d
. Using Bayesian interior structure retrieval models, we show that the amount of gas in the planets does not vary in a monotonous way, contrary to what one would expect from simple formation and evolution models and unlike other known systems in a chain of Laplace resonances. The brightness of TOI-178 (
H
= 8.76 mag,
J
= 9.37 mag,
V
= 11.95 mag) allows for a precise characterisation of its orbital architecture as well as of the physical nature of the six presently known transiting planets it harbours. The peculiar orbital configuration and the diversity in average density among the planets in the system will enable the study of interior planetary structures and atmospheric evolution, providing important clues on the formation of super-Earths and mini-Neptunes.
More extensive use of metagenomic shotgun sequencing in microbiome research relies on the development of high-throughput, cost-effective sequencing. Here we present a comprehensive evaluation of the ...performance of the new high-throughput sequencing platform BGISEQ-500 for metagenomic shotgun sequencing and compare its performance with that of 2 Illumina platforms.
Using fecal samples from 20 healthy individuals, we evaluated the intra-platform reproducibility for metagenomic sequencing on the BGISEQ-500 platform in a setup comprising 8 library replicates and 8 sequencing replicates. Cross-platform consistency was evaluated by comparing 20 pairwise replicates on the BGISEQ-500 platform vs the Illumina HiSeq 2000 platform and the Illumina HiSeq 4000 platform. In addition, we compared the performance of the 2 Illumina platforms against each other. By a newly developed overall accuracy quality control method, an average of 82.45 million high-quality reads (96.06% of raw reads) per sample, with 90.56% of bases scoring Q30 and above, was obtained using the BGISEQ-500 platform. Quantitative analyses revealed extremely high reproducibility between BGISEQ-500 intra-platform replicates. Cross-platform replicates differed slightly more than intra-platform replicates, yet a high consistency was observed. Only a low percentage (2.02%-3.25%) of genes exhibited significant differences in relative abundance comparing the BGISEQ-500 and HiSeq platforms, with a bias toward genes with higher GC content being enriched on the HiSeq platforms.
Our study provides the first set of performance metrics for human gut metagenomic sequencing data using BGISEQ-500. The high accuracy and technical reproducibility confirm the applicability of the new platform for metagenomic studies, though caution is still warranted when combining metagenomic data from different platforms.
Meltwater discharge from tidewater glaciers impacts the adjacent marine environment. Due to global warming tidewater glaciers are retreating and will eventually terminate on land. Yet, the mechanisms ...through which meltwater runoff and subglacial discharge from tidewater glaciers influence marine primary production remain poorly understood, as data in close proximity to glacier fronts are scarce. Here, we show that subglacial meltwater discharge and bedrock characteristics of the catchments control the phytoplankton growth environment inside the fjord, based on data collected in close proximity to tidewater glacier fronts in Kongsfjorden, Svalbard from 26 to 31 July 2017. In the southern part of the inner fjord, glacial meltwater from subglacial discharge was rich in fine sediments derived from erosion of Devonian Old Red Sandstone and carbonate rock deposits, limiting light availability for phytoplankton (0.6 mg m–3 Chl a on average, range 0.2-1.9 mg m-3). In contrast, coarser sediments derived from gneiss and granite bedrock and lower subglacial discharge rates were associated with more favourable light conditions facilitating a local phytoplankton bloom in the northern part of the inner fjord with mean Chl a concentration of 2.8 mg m-3 (range 1.3-7.4 mg m-3). In the northern part, glacier meltwater was a direct source of silicic acid through weathering of the silica-rich gneiss and granite bedrock. Upwelling of the subglacial freshwater discharge plume at the Kronebreen glacier front in the southern part entrained large volumes of ambient, nutrient-rich bottom waters which led to elevated surface concentrations of ammonium, nitrate and partly silicic acid. Total dissolved inorganic nitrogen transported to the surface with the upwelling of the subglacial discharge plume has a significant potential to enhance summer primary production in Kongsfjorden, with ammonium released from the seafloor being of particular importance. The transition from tidewater to land-terminating glaciers may, thus reduce the input of nutrients to the surface layer with negative consequences for summer productivity.
The Yamnaya expansions from the western steppe into Europe and Asia during the Early Bronze Age (~3000 BCE) are believed to have brought with them Indo-European languages and possibly horse ...husbandry. We analyzed 74 ancient whole-genome sequences from across Inner Asia and Anatolia and show that the Botai people associated with the earliest horse husbandry derived from a hunter-gatherer population deeply diverged from the Yamnaya. Our results also suggest distinct migrations bringing West Eurasian ancestry into South Asia before and after, but not at the time of, Yamnaya culture. We find no evidence of steppe ancestry in Bronze Age Anatolia from when Indo-European languages are attested there. Thus, in contrast to Europe, Early Bronze Age Yamnaya-related migrations had limited direct genetic impact in Asia.
Invasive lobular breast carcinoma (ILC) is the second most common breast carcinoma (BC) subtype and is mainly driven by loss of E‐cadherin expression. Correct classification of BC as ILC is important ...for patient treatment. This study assessed the degree of agreement among pathologists for the diagnosis of ILC. Two sets of hormone receptor (HR)‐positive/HER2‐negative BCs were independently reviewed by participating pathologists. In set A (61 cases), participants were provided with hematoxylin/eosin (HE)‐stained sections. In set B (62 cases), participants were provided with HE‐stained sections and E‐cadherin immunohistochemistry (IHC). Tumor characteristics were balanced. Participants classified specimens as non‐lobular BC versus mixed BC versus ILC. Pairwise inter‐observer agreement and agreement with a pre‐defined reference diagnosis were determined with Cohen's kappa statistics. Subtype calls were correlated with molecular features, including CDH1/E‐cadherin mutation status. Thirty‐five pathologists completed both sets, providing 4,305 subtype calls. Pairwise inter‐observer agreement was moderate in set A (median κ = 0.58, interquartile range IQR: 0.48–0.66) and substantial in set B (median κ = 0.75, IQR: 0.56–0.86, p < 0.001). Agreement with the reference diagnosis was substantial in set A (median κ = 0.67, IQR: 0.57–0.75) and almost perfect in set B (median κ = 0.86, IQR: 0.73–0.93, p < 0.001). The median frequency of CDH1/E‐cadherin mutations in specimens classified as ILC was 65% in set A (IQR: 56–72%) and 73% in set B (IQR: 65–75%, p < 0.001). Cases with variable subtype calls included E‐cadherin‐positive ILCs harboring CDH1 missense mutations, and E‐cadherin‐negative ILCs with tubular elements and focal P‐cadherin expression. ILCs with trabecular growth pattern were often misclassified as non‐lobular BC in set A but not in set B. In conclusion, subtyping of BC as ILC achieves almost perfect agreement with a pre‐defined reference standard, if assessment is supported by E‐cadherin IHC. CDH1 missense mutations associated with preserved E‐cadherin protein expression, E‐ to P‐cadherin switching in ILC with tubular elements, and trabecular ILC were identified as potential sources of discordant classification.
To investigate the influence of left ventricular (LV) lead position on LV dyssynchrony in cardiac resynchronization therapy (CRT).
The LV lead was prospectively targeted to the latest activated LV ...segment (concordant) evaluated by two-dimensional speckle tracking radial strain (ST-RS) echocardiography in 103 CRT recipients (67 ± 12 years). Mechanical dyssynchrony was assessed by anteroseptal-to-posterior (AS-P) delay and interventricular mechanical delay (IVMD). Concordant LV leads were obtained in 72 (70%) patients. Superior LV reverse remodelling (LV-RR; ≥ 15% LV end-systolic volume reduction at 6-month follow-up) was observed in the concordant LV leads compared with the discordant LV leads 51 (76%) vs. 13 (45%); P = 0.003. Mechanical resynchronization responders (≥ 50% AS-P delay reduction at 6-month follow-up) obtained in the concordant LV leads 44 (66%) was greater than in the discordant LV leads 10 (34%); P = 0.005. The discordant LV leads located adjacent to the concordant LV leads (+1 segment; n = 22) and 2 segments apart (+2 segments; n = 9) were evaluated in a subgroup analysis. Mechanical resynchronization responders 6 months after CRT were as follows: in +1 segment n = 10 (48%) and in +2 segments (n = 0; P = 0.001). The concordant LV lead was the only independent predictor of LV-RR at 6-month follow-up (odds ratio, 4.177; P = 0.004). Independent predictors of mechanical resynchronization responders were AS-P delay (odds ratio, 1.007; P = 0.032), IVMD (odds ratio, 1.024; P = 0.038), and concordant LV lead (odds ratio, 4.691; P = 0.004).
Concordant LV leads in CRT provided more responders according to both LV reverse remodelling and mechanical resynchronization.
Objective
: Two extracorporeal membrane oxygenation (ECMO) circuits for children under 10 kg were evaluated and compared for plasma leakage, hemolysis, blood transfusions, and durability. Methods: ...Group A (n
= 20) was supported by ECMO circuits with the Minimax oxygenator and the Biomedicus centrifugal pump. Group B (n
= 10) was supported by ECMO circuits with the Lilliput 2 ECMO oxygenator and the Rotaflow centrifugal pump. Results: ECMO circuit durability, as measured by oxygenator lifespan, was significantly better in Group B than in Group A (p = 0.04). There was significantly lower hemolysis, measured by plasma free hemoglobin, in Group B (p
= 0.019), and patients in Group B had significantly less need for antithrombin III transfusion (p
= 0.004). No plasma leakage was observed in Group B oxygenators, but plasma leakage was observed in all Group A oxygenators. Conclusion: The combination of a Rotaflow centrifugal pump and Lilliput 2 ECMO oxygenator in pediatric ECMO circuits improved durability and reduced circuit-induced hemolysis. This improvement may be due to the low priming volume, the oxygenator's plasma leakage resistance, the suspended rotor of the centrifugal pump, or a combination of these factors.
Perfusion (2007) 22, 323—326.
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