Left ventricular dysfunction after open repair of simple congenital heart defects in infants and children: Quantitation with the use of a conductance catheter immediately after bypass

AbstractObjective: Quantification of myocardial injury after the simplest pediatric operations by load-independent indices of left ventricular function, using conductance and Mikro-Tip pressure catheters (Millar Instruments, Inc., Houston, Tex.) inserted through the left ventricular apex. Methods: Sixteen infants and children with intact ventricular septum undergoing cardiac operations had left ventricular function measured, immediately before and after bypass. Real-time pressure-volume loops were generated by conductance and Mikro-Tip pressure catheters placed in the long-axis via the left ventricular apex, and preload was varied by transient snaring of the inferior vena cava. Results: Good quality pressure-volume loops were generated in 13 patients (atrial septal defects, n = 11; double-chambered right ventricle, n = 1; supravalvular aortic stenosis, n = 1; age 0.25 to 14.4 years, weight 3.1 to 46.4 kg). Their mean bypass time was 41 ± 14 minutes and mean aortic crossclamp time 27 ± 11 minutes. End-systolic elastance decreased by 40.7% from 0.34 ± 0.17 to 0.21 ± 0.15 mm Hg-1·ml-1·kg-1 (p < 0.001). There were no significant changes in the slope of the stroke work–end-diastolic volume relationship, end-diastolic elastance, time constant of isovolumic relaxation, and normalized values of the maxima and minima of the first derivative of developed left ventricular pressure. Conclusion: Load-independent indices of left ventricular function can be derived from left ventricular pressure-volume loops generated by conductance and Mikro-Tip pressure catheters during the perioperative period in infants and children undergoing cardiac operations. Incomplete myocardial protection was demonstrated by a deterioration in systolic function after even short bypass and crossclamp times.Ignorance of the cause of postoperative myocardial dysfunction in the immature heart is compounded by the incomplete myocardial protection afforded by current cardioplegic strategies.1,5 Investigations of the mechanisms and treatment of postoperative ventricular dysfunction are hampered by use of nonspecific clinical end points as indirect estimates of ventricular function, for example, requirement for inotropic agents, duration of ventilation, intensive care unit stay, and mortality. These clinical indices are relatively insensitive to changes in ventricular function and necessitate large cohorts of patients to detect even major differences in outcome from differing myocardial protective strategies.To measure left ventricular function optimally during the perioperative period, with its dramatic changes in loading conditions, necessitates the use of load-independent indices of systolic and diastolic function. In infants and children with an intact ventricular septum undergoing cardiac operations (mainly atrial septal defect closure), we report the changes in left ventricular function assessed from the pressure-volume plane with the use of a conductance catheter and Mikro-Tip pressure catheter (Millar Instruments, Inc., Houston, Tex). In animal and human studies the conductance catheter is placed in the long axis of the left ventricle, most commonly through the aortic valve, with the use of retrograde arterial cannulation or aortotomy.6-11 This is clearly impractical in children undergoing bypass procedures, and in this study we report the first clinical use of custom-built miniature catheters placed in the same long axis, but via the left ventricular apex

Towards an effective potential for the monomer, dimer, hexamer, solid and liquid forms of hydrogen fluoride

We present an attempt to build up a new two-body effective potential for hydrogen fluoride, fitted to theoretical and experimental data relevant not only to the gas and liquid phases, but also to the crystal. The model is simple enough to be used in Molecular Dynamics and Monte Carlo simulations. The potential consists of: a) an intra-molecular contribution, allowing for variations of the molecular length, plus b) an inter-molecular part, with three charged sites on each monomer and a Buckingham "exp-6" interaction between fluorines. The model is able to reproduce a significant number of observables on the monomer, dimer, hexamer, solid and liquid forms of HF. The shortcomings of the model are pointed out and possible improvements are finally discussed.Comment: LaTeX, 24 pages, 2 figures. For related papers see also http://www.chim.unifi.it:8080/~valle

Evidence of a recent decline in UK emissions of hydrofluorocarbons determined by the InTEM inverse model and atmospheric measurements

National greenhouse gas inventories (GHGIs) are submitted annually to the United Nations Framework Convention on Climate Change (UNFCCC). They are estimated in compliance with Intergovernmental Panel on Climate Change (IPCC) methodological guidance using activity data, emission factors and facility-level measurements. For some sources, the outputs from these calculations are very uncertain. Inverse modelling techniques that use high-quality, long-term measurements of atmospheric gases have been developed to provide independent verification of national GHGIs. This is considered good practice by the IPCC as it helps national inventory compilers to verify reported emissions and to reduce emission uncertainty. Emission estimates from the InTEM (Inversion Technique for Emission Modelling) model are presented for the UK for the hydrofluorocarbons (HFCs) reported to the UNFCCC (HFC-125, HFC-134a, HFC-143a, HFC-152a, HFC-23, HFC-32, HFC-227ea, HFC-245fa, HFC-43-10mee and HFC-365mfc). These HFCs have high global warming potentials (GWPs), and the global background mole fractions of all but two are increasing, thus highlighting their relevance to the climate and a need for increasing the accuracy of emission estimation for regulatory purposes. This study presents evidence that the long-term annual increase in growth of HFC-134a has stopped and is now decreasing. For HFC-32 there is an early indication, its rapid global growth period has ended, and there is evidence that the annual increase in global growth for HFC-125 has slowed from 2018. The inverse modelling results indicate that the UK implementation of European Union regulation of HFC emissions has been successful in initiating a decline in UK emissions from 2018. Comparison of the total InTEM UK HFC emissions in 2020 with the average from 2009-2012 shows a drop of 35ĝ€¯%, indicating progress toward the target of a 79ĝ€¯% decrease in sales by 2030. The total InTEM HFC emission estimates (2008-2018) are on average 73 (62-83)ĝ€¯% of, or 4.3 (2.7-5.9)ĝ€¯Tgĝ€¯CO2-eqĝ€¯yr-1 lower than, the total HFC emission estimates from the UK GHGI. There are also significant discrepancies between the two estimates for the individual HFCs.</p

Evidence of a recent decline in UK emissions of hydrofluorocarbons determined by the InTEM inverse model and atmospheric measurements

National greenhouse gas inventories (GHGIs) are submitted annually to the United Nations Framework Convention on Climate Change (UNFCCC). They are estimated in compliance with Intergovernmental Panel on Climate Change (IPCC) methodological guidance using activity data, emission factors and facility-level measurements. For some sources, the outputs from these calculations are very uncertain. Inverse modelling techniques that use high-quality, long-term measurements of atmospheric gases have been developed to provide independent verification of national GHGIs. This is considered good practice by the IPCC as it helps national inventory compilers to verify reported emissions and to reduce emission uncertainty. Emission estimates from the InTEM (Inversion Technique for Emission Modelling) model are presented for the UK for the hydrofluorocarbons (HFCs) reported to the UNFCCC (HFC-125, HFC-134a, HFC-143a, HFC-152a, HFC-23, HFC-32, HFC-227ea, HFC-245fa, HFC-43-10mee and HFC-365mfc). These HFCs have high global warming potentials (GWPs), and the global background mole fractions of all but two are increasing, thus highlighting their relevance to the climate and a need for increasing the accuracy of emission estimation for regulatory purposes. This study presents evidence that the long-term annual increase in growth of HFC-134a has stopped and is now decreasing. For HFC-32 there is an early indication, its rapid global growth period has ended, and there is evidence that the annual increase in global growth for HFC-125 has slowed from 2018. The inverse modelling results indicate that the UK implementation of European Union regulation of HFC emissions has been successful in initiating a decline in UK emissions from 2018. Comparison of the total InTEM UK HFC emissions in 2020 with the average from 2009–2012 shows a drop of 35 %, indicating progress toward the target of a 79 % decrease in sales by 2030. The total InTEM HFC emission estimates (2008–2018) are on average 73 (62–83) % of, or 4.3 (2.7–5.9) Tg CO2-eq yr−1 lower than, the total HFC emission estimates from the UK GHGI. There are also significant discrepancies between the two estimates for the individual HFCs.</p

Primitive computations in speech processing

Previous research suggests that artificial-language learners exposed to quasi-continuous speech can learn that the first and the last syllables of words have to belong to distinct classes (e.g., Endress & Bonatti, 2007; Peña, Bonatti, Nespor, & Mehler, 2002). The mechanisms of these generalizations, however, are debated. Here we show that participants learn such generalizations only when the crucial syllables are in edge positions (i.e., the first and the last), but not when they are in medial positions (i.e., the second and the fourth in pentasyllabic items). In contrast to the generalizations, participants readily perform statistical analyses also in word middles. In analogy to sequential memory, we suggest that participants extract the generalizations using a simple but specific mechanism that encodes the positions of syllables that occur in edges. Simultaneously, they use another mechanism to track the syllable distribution in the speech streams. In contrast to previous accounts, this model explains why the generalizations are faster than the statistical computations, require additional cues, and break down under different conditions, and why they can be performed at all. We also show that that similar edge-based mechanisms may explain many results in artificial-grammar learning and also various linguistic observations

Remote ischemic conditioning: from experimental observation to clinical application: report from the 8th Biennial Hatter Cardiovascular Institute Workshop

In 1993, Przyklenk and colleagues made the intriguing experimental observation that 'brief ischemia in one vascular bed also protects remote, virgin myocardium from subsequent sustained coronary artery occlusion' and that this effect '.... may be mediated by factor(s) activated, produced, or transported throughout the heart during brief ischemia/reperfusion'. This seminal study laid the foundation for the discovery of 'remote ischemic conditioning' (RIC), a phenomenon in which the heart is protected from the detrimental effects of acute ischemia/reperfusion injury (IRI), by applying cycles of brief ischemia and reperfusion to an organ or tissue remote from the heart. The concept of RIC quickly evolved to extend beyond the heart, encompassing inter-organ protection against acute IRI. The crucial discovery that the protective RIC stimulus could be applied non-invasively, by simply inflating and deflating a blood pressure cuff placed on the upper arm to induce cycles of brief ischemia and reperfusion, has facilitated the translation of RIC into the clinical setting. Despite intensive investigation over the last 20 years, the underlying mechanisms continue to elude researchers. In the 8th Biennial Hatter Cardiovascular Institute Workshop, recent developments in the field of RIC were discussed with a focus on new insights into the underlying mechanisms, the diversity of non-cardiac protection, new clinical applications, and large outcome studies. The scientific advances made in this field of research highlight the journey that RIC has made from being an intriguing experimental observation to a clinical application with patient benefit

AGL StimSelect: Software for automated selection of stimuli for artificial grammar learning

Artificial Grammar Learning (AGL) is an experimental paradigm that has been used extensively in cognitive research for many years to study implicit learning, associative learning, and generalization based either on similarity or rules. Without computer assistance it is virtually impossible to generate appropriate grammatical training stimuli along with grammatical or non-grammatical test stimuli that control relevant psychological variables. We present the first flexible, fully automated software for selecting AGL stimuli. The software allows users to specify a grammar of interest, and to manipulate characteristics of training and test sequences, and their relationship to each other. The user thus has direct control over stimulus features that may influence learning and generalization in AGL tasks. The software enables researchers to develop AGL designs that would not be feasible without automatic stimulus selection. It is implemented in Matlab

A renewed rise in global HCFC-141b emissions between 2017???2021

Global emissions of the ozone-depleting gas HCFC-141b (1,1-dichloro-1-fluoroethane, CH3CCl2F) derived from measurements of atmospheric mole fractions increased between 2017 and 2021 despite a fall in reported production and consumption of HCFC-141b for dispersive uses. HCFC-141b is a controlled substance under the Montreal Protocol, and its phase-out is currently underway, after a peak in reported consumption and production in developing (Article 5) countries in 2013. If reported production and consumption are correct, our study suggests that the 2017–2021 rise is due to an increase in emissions from the bank when appliances containing HCFC-141b reach the end of their life, or from production of HCFC-141b not reported for dispersive uses. Regional emissions have been estimated between 2017–2020 for all regions where measurements have sufficient sensitivity to emissions. This includes the regions of northwestern Europe, east Asia, the United States and Australia, where emissions decreased by a total of 2.3 ± 4.6 Gg yr−1, compared to a mean global increase of 3.0 ± 1.2 Gg yr−1 over the same period. Collectively these regions only account for around 30 % of global emissions in 2020. We are not able to pinpoint the source regions or specific activities responsible for the recent global emission rise

Simvastatin inhibits TGFβ1-induced fibronectin in human airway fibroblasts

<p>Abstract</p> <p>Background</p> <p>Bronchial fibroblasts contribute to airway remodelling, including airway wall fibrosis. Transforming growth factor (TGF)-β1 plays a major role in this process. We previously revealed the importance of the mevalonate cascade in the fibrotic response of human airway smooth muscle cells. We now investigate mevalonate cascade-associated signaling in TGFβ1-induced fibronectin expression by bronchial fibroblasts from non-asthmatic and asthmatic subjects.</p> <p>Methods</p> <p>We used simvastatin (1-15 μM) to inhibit 3-hydroxy-3-methlyglutaryl-coenzyme A (HMG-CoA) reductase which converts HMG-CoA to mevalonate. Selective inhibitors of geranylgeranyl transferase-1 (GGT1; GGTI-286, 10 μM) and farnesyl transferase (FT; FTI-277, 10 μM) were used to determine whether GGT1 and FT contribute to TGFβ1-induced fibronectin expression. In addition, we studied the effects of co-incubation with simvastatin and mevalonate (1 mM), geranylgeranylpyrophosphate (30 μM) or farnesylpyrophosphate (30 μM).</p> <p>Results</p> <p>Immunoblotting revealed concentration-dependent simvastatin inhibition of TGFβ1 (2.5 ng/ml, 48 h)-induced fibronectin. This was prevented by exogenous mevalonate, or isoprenoids (geranylgeranylpyrophosphate or farnesylpyrophosphate). The effects of simvastatin were mimicked by GGTI-286, but not FTI-277, suggesting fundamental involvement of GGT1 in TGFβ1-induced signaling. Asthmatic fibroblasts exhibited greater TGFβ1-induced fibronectin expression compared to non-asthmatic cells; this enhanced response was effectively reduced by simvastatin.</p> <p>Conclusions</p> <p>We conclude that TGFβ1-induced fibronectin expression in airway fibroblasts relies on activity of GGT1 and availability of isoprenoids. Our results suggest that targeting regulators of isoprenoid-dependent signaling holds promise for treating airway wall fibrosis.</p