Effects of Age and Comorbidities on Intensive Care and 1-year Mortality after HeartMate 3 Implantation

Background: The use of left ventricular assist devices (LVAD) has been rapidly increasing in older people over the past two decades due to their availability as destination therapy. This study aimed to assess the effect of age and comorbidities on the intensive care unit (ICU) and 1-year mortality after HeartMate 3 LVAD implantation. Methods: From 2016 to 2023, all consecutive adult patients implanted with HeartMate 3 LVAD in our tertiary referral center were enrolled in the study. Patients were stratified according to their age at implantation into Group-1 (&lt;45 years), Group-2 (46–64 years), and Group-3 (&gt;65 years). The effect of age and comorbidities on ICU and 1-year mortality were assessed. Results: In total, 135 patients were included (mean age 54±13 years, 79% males). Baseline vital signs, comorbidities, and hemodynamic support were not different between age groups. The older population had significantly lower eGFR (p=0.025), ischemic cardiac diseases as the underlying heart problem (p&lt;0.001), and LVAD as destination therapy (p&lt;0.001). The mortality rate at the ICU and at one year were 90% and 83%, respectively. The median age of the patients who died in the ICU was significantly higher than 63 [56–65] years versus 57 years [49–62, p=0.034). However, age lost its significance with logistic regression analysis. Having a recent major myocardial infarct, high preoperative leukocyte count, and cardiopulmonary bypass time were independent risk factors for ICU mortality. On the other hand, age was an independent risk factor for one-year mortality. Conclusion: Older age predicts increased one-year but not ICU mortality after HeartMate 3 LVAD implantation, while recent major myocardial infarction, high preoperative leukocyte count, and longer cardiopulmonary bypass time were independent risk factors for ICU mortality. Careful patient selection is critical to optimize outcomes after HeartMate 3 LVAD implantation.</p

An Agent-Based Computational Economics Approach To Technology Adoption Timing And The Emergence Of Dominant Designs

Dominant technology designs emerge as the sum of adoption decisions across many firms. We take the position that if certain factors drive adoption by an individual firm, then in the aggregate, they may also illuminate the conditions under which a particular dominant design might emerge. In order to show this, we develop an agent-based computational model to explore linkages between firm specific, industry, and environmental factors, such as knowledge overlap, firm size, environmental uncertainty, and the scope of returns to adoption. We show that the significance of these factors varies with the stage of the technology contest. Early in the process, firms that have a compelling reason to adopt (such as to avoid obsolescence of key resources) choose to enter to create momentum for a particular approach. Other firms, due to indifference, inability or uncertainty, may defer until outcomes are clearer or choose not to adopt at all. More importantly, what constitutes a compelling reason for adoption varies with the nature of the firms that lead as innovators and the external environmental factors. On a broad scale, strong regularities in adoption timing and characteristics of technology winners emerge from the analysis

Monitoring of yeast metabolism with calorimetry

A system for calorimetric measurements is established in a 1500 L pilot bioreactor. Saccharomyces cerevisiae, baker’s yeast has three metabolic pathways: 1) purely oxidative, glucose consuming; 2) purely reductive, glucose consuming and ethanol producing and 3) purely oxidative, ethanol consuming. Designing experiments to lead the yeast to a single pathway, the accuracy of the calorimetric measurements are verified. Using on-line data of microbial heat production and substrate consumption, the combustion enthalpies of glucose and ethanol in purely oxidative (aerobic) fed batch fermentations are determined as 15900 and 29000 kJ/kg respectively, Combustion enthalpy of glucose in purely reductive (anaerobic) environment is determined as 511 kJ/kg. These values are in good corresponding with literature data. It is now possible to determine the fraction of substrate uptake utilized for energy (catabolism, k) and biosynthesis (anabolism, a) metabolisms on-line. In oxidative (aerobic) fermentations we determined kSox=0.45 for glucose, kEox=0.63 for ethanol and in reductive (anaerobic) fermentations kSred=0.96 for glucose; the anabolism factors are aSox=0.55, aEox=0.37 and aSred=0.04 respectively. The single pathways can occur together so that an experiment is designed with changing environmental conditions to prove the overall calorimetric model. The result is that measured and the calculated microbial heat energy rates are in good accordance. Calorimetric measurements can be used to monitor yeast metabolism on-line, for advanced control strategies or, to predict fermentations or for designing heat exchanger or bioreactor systems

Animal Models for Limbal Stem Cell Deficiency: A Critical Narrative Literature Review

\ua9 2024, The Author(s). This literature review will provide a critical narrative overview of the highlights and potential pitfalls of the reported animal models for limbal stem cell deficiency (LSCD) and will identify the neglected aspects of this research area. There exists significant heterogeneity in the literature regarding the methodology used to create the model and the predefined duration after the insult when the model is supposedly fully fit for evaluations and/or for testing various therapeutic interventions. The literature is also replete with examples wherein the implementation of a specific model varies significantly across different studies. For example, the concentration of the chemical, as well as its duration and technique of exposure in a chemically induced LSCD model, has a great impact not only on the validity of the model but also on the severity of the complications. Furthermore, while some models induce a full-blown clinical picture of total LSCD, some are hindered by their ability to yield only partial LSCD. Another aspect to consider is the nature of the damage induced by a specific method. As thermal methods cause more stromal scarring, they may be better suited for assessing the anti-fibrotic properties of a particular treatment. On the other hand, since chemical burns cause more neovascularisation, they provide the opportunity to tap into the potential treatments for anti-neovascularisation. The animal species (i.e., rats, mice, rabbits, etc.) is also a crucial factor in the validity of the model and its potential for clinical translation, with each animal having its unique set of advantages and disadvantages. This review will also elaborate on other overlooked aspects, such as the anaesthetic(s) used during experiments, the gender of the animals, care after LSCD induction, and model validation. The review will conclude by providing future perspectives and suggestions for further developments in this rather important area of research

Identification of parvalbumin interneurons as cellular substrate of fear memory persistence

Parvalbumin-positive (PV) basket cells provide perisomatic inhibition in the cortex and hippocampus and control generation of memory-related network activity patterns, such as sharp wave ripples (SPW-R). Deterioration of this class of fast-spiking interneurons has been observed in neuropsychiatric disorders and evidence from animal models suggests their involvement in the acquisition and extinction of fear memories. Here, we used mice with neuron type-targeted expression of the presynaptic gain-of-function glycine receptor RNA variant GlyR {beta}3L(185L) to genetically enhance the network activity of PV interneurons. These mice showed reduced extinction of contextual fear memory but normal auditory cued fear memory. They furthermore displayed increase of SPW-R activity in area CA3 and CA1 and facilitated propagation of this particular network activity pattern, as determined in ventral hippocampal slice preparations. Individual freezing levels during extinction and SPW-R propagation were correlated across genotypes. The same was true for parvalbumin immunoreactivity in the ventral hippocampus, which was generally augmented in the GlyR mutant mice and correlated with individual freezing levels. Together, these results identify PV interneurons as critical cellular substrate of fear memory persistence and associated SPW-R activity in the hippocampus. Our findings may be relevant for the identification and characterization of physiological correlates for posttraumatic stress and anxiety disorders

Dynamical transition, hydrophobic interface, and the temperature dependence of electrostatic fluctuations in proteins

Molecular dynamics simulations have revealed a dramatic increase, with increasing temperature, of the amplitude of electrostatic fluctuations caused by water at the active site of metalloprotein plastocyanin. The increased breadth of electrostatic fluctuations, expressed in terms of the reorganization energy of changing the redox state of the protein, is related to the formation of the hydrophobic protein/water interface allowing large-amplitude collective fluctuations of the water density in the protein's first solvation shell. On the top of the monotonic increase of the reorganization energy with increasing temperature, we have observed a spike at 220 K also accompanied by a significant slowing of the exponential collective Stokes shift dynamics. In contrast to the local density fluctuations of the hydration-shell waters, these spikes might be related to the global property of the water solvent crossing the Widom line.Comment: 9 pages, 8 figure

Theory of biopolymer stretching at high forces

We provide a unified theory for the high force elasticity of biopolymers solely in terms of the persistence length, $\xi_p$, and the monomer spacing, $a$. When the force f>\fh \sim k_BT\xi_p/a^2 the biopolymers behave as Freely Jointed Chains (FJCs) while in the range \fl \sim k_BT/\xi_p < f < \fh the Worm-like Chain (WLC) is a better model. We show that $\xi_p$ can be estimated from the force extension curve (FEC) at the extension $x\approx 1/2$ (normalized by the contour length of the biopolymer). After validating the theory using simulations, we provide a quantitative analysis of the FECs for a diverse set of biopolymers (dsDNA, ssRNA, ssDNA, polysaccharides, and unstructured PEVK domain of titin) for $x \ge 1/2$. The success of a specific polymer model (FJC or WLC) to describe the FEC of a given biopolymer is naturally explained by the theory. Only by probing the response of biopolymers over a wide range of forces can the $f$-dependent elasticity be fully described.Comment: 20 pages, 4 figure

The HgMn Binary Star Phi Herculis: Detection and Properties of the Secondary and Revision of the Elemental Abundances of the Primary

Observations of the Mercury-Manganese star Phi Herculis with the Navy Prototype Optical Interferometer (NPOI) conclusively reveal the previously unseen companion in this single-lined binary system. The NPOI data were used to predict a spectral type of A8V for the secondary star Phi Her B. This prediction was subsequently confirmed by spectroscopic observations obtained at the Dominion Astrophysical Observatory. Phi Her B is rotating at 50 +/-3 km/sec, in contrast to the 8 km/sec lines of Phi Her A. Recognizing the lines from the secondary permits one to separate them from those of the primary. The abundance analysis of Phi Her A shows an abundance pattern similar to those of other HgMn stars with Al being very underabundant and Sc, Cr, Mn, Zn, Ga, Sr, Y, Zr, Ba, Ce, and Hg being very overabundant.Comment: Accepted to ApJ, 45 pages, 11 figure

First-Line Support by Intra-Aortic Balloon Pump in Non-Ischaemic Cardiogenic Shock in the Era of Modern Ventricular Assist Devices

Objectives: Little is known about circulatory support in cardiogenic shock (CS) from other causes than the acute coronary syndrome or after cardiotomy. We evaluated the effects of first-line intra-aortic balloon pump (IABP) support in this subpopulation of CS patients. Methods: A retrospective study was performed in 27 patients with CS from end-stage cardiomyopathy supported firstly by IABP in the years 2011-2016. Results: At 24 h, lactate decreased from 3.2 (2.1-6.8) to 1.8 (1.2-2.2) mmol/L (p < 0.001). Eighteen patients (67%) defined as IABP responders were successfully bridged to either recovery (n = 7), left ventricular assist device (n = 5), or heart transplantation (n = 6). IABP failed in 9 patients (non-responders, 33%) who either died (n = 7) or needed support by extracorporeal membrane oxygenation (n = 2). At 24 h of IABP support, urinary output was higher (2,660 [1,835-4,440] vs. 1,200 [649-2,385] mL; p = 0.02) and fluid balance more negative (-1,564 [-2,673 to -1,086] vs. -500 [-930 to +240] mL; p < 0.001) in responders than non-responders. Overall survival at 1 year was 63%. Conclusion: In most patients, first-line support by IABP in end-stage cardiomyopathy is associated with improvement in organ perfusion and clinical stabilisation for at least 24 h allowing time for decision making on next therapies