Infinite Generation of Language Unreachable From a Stepwise Approach.

Language is commonly thought of as a culturally evolved system of communication rather than a computational system for generating linguistic objects that express thought. Furthermore, language is commonly argued to have gradually evolved from finite proto-language which eventually developed into infinite language of modern humans. Both ideas are typically integrated in accounts that attempt to explain gradual evolution of more complex language from the increasingly strong pressures of communicative needs. Recently some arguments have been presented that the probability of the emergence of infinitely productive languages is increased by communicative pressures. These arguments fail. The question whether decidable languages evolve into infinite language is vacuous since infinite generation is the null hypothesis for a generative procedure. The argument that increasing cardinality leads to infinite language is incoherent since it essentially conflates concepts of performance with notions of competence. Recursive characterization of infinite language is perfectly consistent with finite output. Further, the discussion completely ignores a basic insight that language is not about decidability of weakly generated strings but rather about properties of strongly generated structures. Finally, the plausibility proof that infinite productivity evolves from finite language is false because it confuses (infinite) cardinal numbers with (natural) ordinal numbers. Infinite generation cannot be reached with a stepwise approach.

Phonemic clicks and the mapping asymmetry: How language emerged and speech developed.

Language existed before human populations became separated (all descendant populations have language) but language did not emerge until long after these population divergences occurred (behavioral modernity only showed then). Distinguishing capacity for language from externalized language resolves the apparent paradox, eliminates the need of proto-language, and rules out monogenesis. Speech emerged only after the capacity for language became (sufficiently) fixated in the species. This accords well with a fundamental property of human language. Rules mapping to meaning rely on structural properties only, while rules mapping to sound are (also) sensitive to linear order, reflecting properties of sensorimotor modalities. The asymmetry suggests (i) primacy of internal language over speech/sign, and (ii) evolution of capacity of language preceding externalized language. Click phonemes with their unique geneological, genetic and geographical distribution may be relevant here. All biologically Khoisan groups speak click languages, which are spoken by biologically Khoisan groups only. Separation followed possession of internal language but preceded externalized language. Clicks were recruited for externalization in San populations only after deepest separation.

Percutaneous coronary intervention without on site surgical back-up; two-years registry of a large Dutch community hospital.

AIMS: To assess safety and efficacy of off-site percutaneous coronary intervention (PCI) in The Dutch invasive cardiovascular system. METHODS AND RESULTS: Descriptive single centre registry of elective and emergency PCI. Setting is a Dutch community hospital, 40 km north of Amsterdam, with an adherent population of 400,000 people. A Clinical follow up of Major Adverse Cardiac and Cerebral Events (MACCE) at 30 days post PCI is performed. The total number of participants eligible for PCI was 781 of whom 545 were men and 236 women. During a two-year period 781 PCI's were performed of which 298 were emergency and 483 elective. Acute complications occurred in 2.1% of participants. MACCE-free was 86.9% in the group with AMI and 95.8% in the elective group. CONCLUSIONS: Off-site PCI is feasible and safe in The Netherlands on the condition that specific key factors for success are taken into consideration.

Increased infiltration of Chlamydophila pneumoniae in the vessel wall of human veins after perfusion.

BACKGROUND: Several studies have suggested an association between Chlamydophila pneumoniae (Cp) infection and atherosclerosis. A recent study detected Cp DNA in the saphenous vein of 12% of all patients before bypass grafting and in 38% of failed grafts. We used a system in which human veins were perfused with autologous blood under arterial pressure. MATERIALS AND METHODS: Veins were surplus segments of saphenous veins of coronary artery bypass grafting (CABG) patients. Vein grafts were perfused with the blood of the same patient after CABG procedures. Veins were analysed for Cp-specific membrane protein using immunohistochemical and PCR analysis. Veins were analysed before and after perfusion (up to 4 h). The number of Cp positive cells was then quantified in the vein layers. RESULTS: Cp protein was detected within macrophages only. In non-perfused veins, Cp was present in the adventitia in 91% of all patients, in the circular (64%) and longitudinal (23%) layer of the media. No positivity was found in the intima. Perfusion subsequently resulted in a significant increase of Cp positive cells within the circular layer of the media that, however, differed strongly between different patients. Cp DNA was not detected by PCR in those specimens. CONCLUSION: Cp protein was present in 91% of veins, but the number of positive cells differed remarkably between patients. Perfusion of veins resulted in increased infiltration of Cp into the circular layer. These results may point to a putative discriminating role of Cp with respect to graft failure between different patients.

Myosin heavy chain composition and the economy of contraction in healthy and diseased human myocardium.

Changes in myosin heavy chain (MHC) isoform expression and protein composition occur during cardiac disease and it has been suggested that even a minor shift in MHC composition may exert a considerable effect on myocardial energetics and performance. Here an overview is provided of the cellular basis of the energy utilisation in cardiac tissue and novel data are presented concerning the economy of myocardial contraction in diseased atrial and ventricular human myocardium. ATP utilisation and force development were measured at various Ca(2+) concentrations during isometric contraction in chemically skinned atrial trabeculae from patients in sinus rhythm (SR) or with chronic atrial fibrillation (AF) and in ventricular muscle strips from non-failing donor or end-stage failing hearts. Contractile protein composition was analysed by one-dimensional gel electrophoresis. Atrial fibrillation was accompanied by a significant shift from the fast alpha-MHC isoform to the slow beta-MHC isoform, whereas both donor and failing ventricular tissue contained almost exclusively the beta-MHC isoform. Simultaneous measurements of force and ATP utilisation indicated that economy of contraction is preserved in atrial fibrillation and in end-stage human heart failure.

The use of a mini bypass system (Cobe Synergy) without venous and cardiotomy reservoir in a mitral valve repair: a case report.

The use of mini cardiopulmonary bypass circuits is an emerging technology. The venous and cardiotomy reservoir have been excluded from the circuit. This results in a reduction of the blood contact surface area and of the priming volume. Entrainment of venous air, however, remains a drawback in the widespread acceptance of using these mini circuits. The technique described resolves this problem by automatic removal of venous air, and explains how this mini cardiopulmonary bypass circuit was utilized on a 64-year-old female presented for a mitral valve repair. In the absence of a cardiotomy reservoir, an autotransfusion cell separator was used to process shed blood and, after CPB, the residual pump blood. This mini bypass circuit, with the safety feature to remove automatically venous air, provided an additional degree of protection. In our experience, mini bypass circuits allow us safely to perform cardiopulmonary bypass during valve procedures.

Myocardial contraction is 5-fold more economical in ventricular than in atrial human tissue.

OBJECTIVE: Cardiac energetics and performance depend on the expression level of the fast (alpha-) and slow (beta-) myosin heavy chain (MHC) isoform. In ventricular tissue, the beta-MHC isoform predominates, whereas in atrial tissue a variable mixture of alpha- and beta-MHC is found. In several cardiac diseases, the slow isoform is upregulated; however, the functional implications of this transition in human myocardium are largely unknown. The aim of this study was to determine the relation between contractile properties and MHC isoform composition in healthy human myocardium using the diversity in atrial tissue. METHODS: Isometric force production and ATP consumption were measured in chemically skinned atrial trabeculae and ventricular muscle strips, and rate of force redevelopment was studied using single cardiomyocytes. MHC isoform composition was determined by one-dimensional SDS-gel electrophoresis. RESULTS: Force development in ventricular tissue was about 5-fold more economical, but nine times slower, than in atrial tissue. Significant linear correlations were found between MHC isoform composition, ATP consumption and rate of force redevelopment. CONCLUSION: These results clearly indicate that even a minor shift in MHC isoform expression has considerable impact on cardiac performance in human tissue.

The impact of heparin-coated cardiopulmonary bypass circuits on pulmonary function and the release of inflammatory mediators.

UNLABELLED: Reduction of the inflammatory reaction with the use of heparin coating has been found during and after cardiopulmonary bypass (CPB). The question remains whether this reduced reaction also decreases the magnitude of CPB-induced pulmonary dysfunction. We therefore evaluated the effects of a heparin-coated circuit versus a similar uncoated circuit on pulmonary indices as well as on inflammatory markers of complement activation (C3b/c), elastase-alpha(1)-antitrypsin complex, and secretory phospholipase A(2) (sPLA(2)) during and after CPB. Fifty-one patients were randomly assigned into two groups undergoing coronary artery bypass grafting with either a heparin-coated (Group 1) or an uncoated (Group 2) circuit. During CPB, a continuous positive airway pressure of 5 cm H(2)O and a fraction of inspired oxygen (FIO(2)) of 0.21 were maintained. Differences in favor of the coated circuit were found in pulmonary shunt fraction (P < 0.05), pulmonary vascular resistance index (P < 0.05), and PaO(2)/FIO(2) ratio (P < 0.05) after CPB and in the intensive care unit. During and after CPB, the coated group demonstrated lower levels of sPLA(2). After CPB, C3b/c and the elastase-alpha(1)-antitrypsin complex were significantly less in the coated group (P < 0.001). The coated circuit was associated with a reduced inflammatory response, decreased pulmonary vascular resistance index and pulmonary shunt fraction, and increased PaO(2)/FIO(2) ratio, suggesting that the coated circuit may have beneficial effects on pulmonary function. The correlation with sPLA(2), leukocyte activation, and postoperative leukocyte count suggests reduced activation of pulmonary capillary endothelial cells. IMPLICATIONS: Heparin coating of the extracorporeal circuit reduces the inflammatory response during cardiopulmonary bypass. Analysis of indices of pulmonary function indicates that use of heparin coating may result in less impaired gas exchange.

Effects of calcium, inorganic phosphate, and pH on isometric force in single skinned cardiomyocytes from donor and failing human hearts.

BACKGROUND: During ischemia, the intracellular calcium and inorganic phosphate (P(i)) concentrations rise and pH falls. We investigated the effects of these changes on force development in donor and failing human hearts to determine if altered contractile protein composition during heart failure changes the myocardial response to Ca(2+), P(i), and pH. METHODS AND RESULTS: Isometric force was studied in mechanically isolated Triton-skinned single myocytes from left ventricular myocardium. Force declined with added P(i) to 0.33+/-0.02 of the control force (pH 7.1, 0 mmol/L P(i)) at 30 mmol/L P(i) and increased with pH from 0.64+/-0.03 at pH 6.2 to 1.27+/-0.02 at pH 7.4. Force dependency on P(i) and pH did not differ between donor and failing hearts. Incubation of myocytes in a P(i)-containing activating solution caused a potentiation of force, which was larger at submaximal than at maximal [Ca(2+)]. Ca(2+) sensitivity of force was similar in donor hearts and hearts with moderate cardiac disease, but in end-stage failing myocardium it was significantly increased. The degree of myosin light chain 2 phosphorylation was significantly decreased in end-stage failing compared with donor myocardium, resulting in an inverse correlation between Ca(2+) responsiveness of force and myosin light chain 2 phosphorylation. CONCLUSIONS: Our results indicate that contractile protein alterations in human end-stage heart failure alter Ca(2+) responsiveness of force but do not affect the force-generating capacity of the cross-bridges or its P(i) and pH dependence. In end-stage failing myocardium, the reduction in force by changes in pH and [P(i)] at submaximal [Ca(2+)] may even be less than in donor hearts because of the increased Ca(2+) responsiveness.

Isometric tension development and its calcium sensitivity in skinned myocyte-sized preparations from different regions of the human heart.

OBJECTIVE: In this study we investigated whether differences exist or develop in patients with aortic or mitral valve disease in myofibrillar contractile function and contractile protein composition between subendo- and subepicardial human ventricular tissue. Isometric tension, its calcium sensitivity and contractile protein composition were studied in left ventricular subendo- and subepicardial and in atrial biopsies obtained during open heart surgery from 24 patients with mitral or aortic valve disease. METHODS: Isometric tension was measured in mechanically isolated skinned myocyte-sized preparations at different free calcium concentrations at 15 degrees C. Protein composition was analysed by one-dimensional gel electrophoresis. A comparison was made between the results of subendo- and subepicardial ventricular tissue within each New York Heart Association class and within the different hemodynamically overloaded groups. RESULTS: Maximal isometric tension was significantly lower in atrial than in ventricular preparations. The concentration of calcium required for half-maximal activation was significantly higher in atrial than in ventricular preparations. Within the ventricle no differences were found in contractile protein composition, isometric tension and its calcium sensitivity between subendo- and subepicardial tissue when all patients were treated as one group or when patients were subdivided according to severity of heart disease or hemodynamic overload. CONCLUSIONS: In this group of patients with ventricular volume or pressure overload no regional differences exist or develop during cardiac disease in left ventricular myofibrillar protein composition and force production. Maximal isometric tension and its calcium sensitivity are smaller in atrial than in ventricular preparations.

Force production in mechanically isolated cardiac myocytes from human ventricular muscle tissue.

OBJECTIVE: The expression of contractile isoforms changes during various pathological conditions but little is known about the consequences of these changes for the mechanical properties in human ventricular muscle. We investigated the feasibility of simultaneous determination of protein composition and isometric force development in single cardiac myocytes from human ventricular muscle tissue obtained from small biopsies taken during open heart surgery. METHODS: Small biopsies of about 3 mg wet weight were taken during open heart surgery from patients with aortic valve stenosis. These biopsies were divided in two parts. One part (approximately 2 mg) was used for mechanical isolation of single myocytes and subsequent force measurement while the remaining part was used, in aliquots of 1 microgram dry weight, for protein analysis by polyacrylamide gel electrophoresis. The myocytes were attached with silicon glue to a sensitive force transducer and a piezoelectric motor, mounted on an inverted microscope and permeabilized by means of Triton X-100. Force development was studied at various free calcium concentrations. RESULTS: From all biopsies, myocytes could be obtained and the composition of contractile proteins could be determined. The average isometric force (+/- s.e.m.) at saturating calcium concentration obtained on 20 myocytes from 5 patients amounted to 51 +/- 8 kN/m2. Force was half maximal at a calcium concentration of 2.47 +/- 0.10 microM. CONCLUSION: These measurements indicate that it is possible to study the correlation between mechanical properties and protein composition in small biopsies from human ventricular muscle.

Standardization of non-invasive impedance cardiography for assessment of stroke volume: comparison with thermodilution.

Since its introduction by Kubicek and colleagues, impedance cardiography has been suggested as a non-invasive, simple, safe and cost-effective method of measuring stroke volume. Several controversial reports on its validity have been published. Pitfalls of this method included the nature of the electrode system and the validity of the equations. Therefore, the purpose of this study was to compare two different spot electrode arrays and the two most frequently used stroke volume equations with each other and with thermodilution. In 37 patients, 24-36 h after cardiac surgery, we performed simultaneous measurements of stroke volume with impedance cardiography (SVIC) and with thermodilution (SVTD). SVIC was obtained using the lateral spot (LS) electrode array, according to Bernstein, and a newly proposed modified semi-circular (MSC) spot electrode array. The equations of Kubicek and Sramek-Bernstein were used to calculate SVIC. The Sramek-Bernstein equation was valid only when the LS array was used; the Kubicek equation determined SVTD correctly only when the MSC array was used. However, a considerably better correlation and agreement (mean difference (2 SD)) was found between SVIC and SVTD for the latter (r = 0.90, 0.5 (17.1) ml vs r = 0.64, -4.9 (31.8) ml for the Sramek-Bernstein equation). We conclude that the most valid measurement of stroke volume using impedance cardiography was obtained when the MSC array was used together with Kubicek's equation.

Impedance cardiography. Importance of the equation and the electrode configuration.

OBJECTIVE: Electrical impedance cardiography (EIC) has been suggested as a non-invasive method to measure cardiac output. In several studies it proved to be a reliable method, although there were some restrictions. In 1966 Kubicek et al. developed an impedance cardiac output system based upon electrodes and a specific stroke volume formula. In 1983 Sramek et al. developed a new electrode configuration, and a new equation to calculate stroke volume, an equation that was adjusted by Bernstein in 1986. Since then these two methods have been used in clinical medicine. The purpose of the present study was to compare both electrode configurations and both stroke volume calculation equations with each other. The cardiac output (CO) values obtained by means of EIC are compared with CO values obtained by means of thermodilution. DESIGN: Prospective study. SETTING: Surgical intensive care unit of a university hospital. PATIENTS: 20 mechanically ventilated patients after cardiac surgery. MEASUREMENTS AND RESULTS: Simultaneous measurement of CO by means of electrical impedance cardiography (COEIC) and thermodilution (COTD) was performed. COEIC was obtained using the lateral spot electrode configuration (LS) and an adjusted circular electrode configuration (SC). The formulas of Sramek (S), Sramek-Bernstein (SB), Kubicek (K) and an adjusted Kubicek formula (aK) were employed. Using the LS electrode configuration, significant differences were found between COEIC and COTD with the S formula (p < 0.005), the K formula (p < 0.001), and the aK formula (p < 0.05). Using the SC electrode configuration, significant differences between COEIC and COTD were found with the K formula (p < 0.005), the S formula (p < 0.01), and the SB formula (p < 0.05). No significant differences was found between EIC and TD using the LS electrode configuration together with the SB formula or using the SC electrode configuration with the aK formula. In both cases a good correlation was found between COEIC and COTD (r = 0.86, p < 0.001 and r = 0.79, p < 0.001, respectively). The mean difference between EIC and TD was 0.15 +/- 0.96 1/min and 0.19 +/- 1.19 1/min, respectively.

Cardiopulmonary bypass with modified fluid gelatin and heparin-coated circuits.

We have assessed the efficacy of cardiopulmonary bypass (CPB) using normal colloid oncotic pressure (COP) in a randomized, controlled study of 20 patients undergoing elective coronary artery surgery using heparin-coated circuits. For CPB, we used either crystalloid priming 1650 ml (n = 10) or colloid priming 1650 ml (2.4% modified fluid gelatin, n = 10). While COP did not change during bypass in the colloid group, a decline was observed in the crystalloid group (P = 0.005). By the end of bypass, the decrease in COP compared with baseline (delta COP) was 8.5 (S.D. 1.1) mm Hg in the crystalloid group compared with 1.5 (2.1) mm Hg in the colloid group (P = 0.0001). delta COP correlated positively with fluid balance during bypass (r2 = 0.41, P = 0.002). Similar increments in complement factors C3b/c and C4b/c, tumour necrosis factor-alpha and neutrophil elastase, but not endotoxins, were found in both groups as indicators of a systemic inflammatory response. A clinical performance score composed of fluid balance, postoperative duration of intubation and the difference between rectal temperature and skin temperature was more favourable in patients treated with colloid priming (P = 0.03). Median postoperative hospital stay was 7 (range 5-16) days in the crystalloid group compared with 5 (4-8) days in the colloid group (P = 0.016). Regression analysis indicated that CPB time, fluid balance during operation and postoperative PO2/FlO2 ratio were independent factors that predicted postoperative hospital stay. From these preliminary results we conclude that in the absence of endotoxaemia, use of a normal COP during CPB with modified fluid gelatin in heparin-coated circuits resulted in an improved postoperative course an a reduction in hospital stay.