A new method to measure oxygenator oxygen transfer performance during cardiopulmonary bypass: clinical testing using the Medtronic Fusion oxygenator.

BACKGROUND: There is no acceptable method of testing oxygen transfer performance in membrane oxygenators quickly and easily during cardiopulmonary bypass. Pre-clinical testing of oxygenators is performed under controlled situations in the laboratory, correlating oxygen transfer to blood flow using 100% oxygen. This laboratory method cannot be used clinically as oxygen transfer values vary significantly at each blood flow and the FiO2 is not kept at 1. Therefore, a formula was developed which corrects the existing FiO2 to attain a PaO2 of 150 mmHg: the corrected FiO2 at 150 mmHg. In graph form, this corrected FiO2 (x-axis) is correlated to the patient's oxygen consumption levels (y-axis), which determines the membrane oxygenator oxygen transfer performance. METHODS: Blood gas and hemodynamic parameters taken during cardiopulmonary bypass using the Medtronic Fusion were used to calculate the oxygen consumption (inlet conditions to the oxygenator) and the corrected FiO2 for a PaO2 of 150 mmHg. Validation of the formula "FiO2-PaO2/(Pb-pH2O)+0.21" was carried out by plotting the calculated values on a graph using PaO2 values between 145 to 155 mmHg and then, using the corrected FiO2 for PaO2s outside of this range. RESULTS: All trend-lines correlated significantly to confirm that the Medtronic Fusion had an extrapolated oxygen transfer of 419 milliliters O2/min at an FiO2 of 1 to achieve a PaO2 of 150 mmHg. CONCLUSIONS: Use of the corrected FiO2 correlated to the oxygen transfer conditions of the membrane oxygenator can easily be used on a routine basis, providing valuable information clinically. When used by the manufacturer under laboratory conditions, further clinically relevant data is provided in terms of FiO2 and resultant PaO2s instead of the present limitations using blood flow. In this way, a clinically justifiable method has been developed to finally establish a standard in testing membrane oxygenator performance.

Why 'class' is too soft a category to capture the explosiveness of social inequality at the beginning of the twenty-first century.

We can distinguish four positions on the continuing, or maybe even increasing, relevance of the category of class at the beginning of the twenty-first century depending on the extent to which they accord central importance to (1) the reproduction or (2) the transformation of social classes with regard to (3) the distribution of goods without bads or (4) the distribution of goods and bads. One could say that Dean Curran introduces the concept of 'risk-class' to radicalize the class distribution of risk and charts who will able to occupy areas less exposed to risk and who will have little choice but to occupy areas that are exposed to the brunt of the fact of the risk society. As he mentioned it is important to note that this social structuring of the distribution of bads will be affected not only by class, but also by other forms of social structuration of disadvantage, such as gender and race. In order to demonstrate that the distribution of bads is currently exacerbating class differences in life chances, however, Curran concentrates exclusively on phenomena of individual risks. In the process, he overlooks the problem of systemic risks in relation of the state, science, new corporate roles, management the mass media, law, mobile capital and social movements; at the same time, his conceptual frame of reference does not really thematize the interdependence between individual and systemic risks. Those who reduce the problematic of risk to that of the life chances of individuals are unable to grasp the conflicting social and political logics of risk and class conflicts. Or, to put it pointedly: 'class' is too soft a category to capture the explosiveness of social inequality in world risk society.

Low fibronectin concentration overcompensates for reduced initial fibroblasts adhesion to a nanoscale topography: single-cell force spectroscopy.

Using single-cell force spectroscopy, we compared the initial adhesion of L929 fibroblasts to planar and nanostructured silicon substrates as a function of fibronectin concentration. The nanostructures were periodically grooved with a symmetric groove-summit period of 180 nm and a groove depth of 120 nm. Cell adhesion strength to the bare nanostructure was lower (79%± 13%) than to the planar substrate, which we attribute to reduced contact area. After pre-incubation with a low fibronectin concentration (5 µg/ml) the adhesion strengths to both surfaces increased, with adhesion strength on the nanostructure outweighing that of the planar substrate by 133%± 14%. At a high fibronectin concentration (25 µg/ml) the adhesion strengths on both surfaces further increased and showed wide variations. In parallel, the nanostructure lost its clear advantage over the planar substrate. Our results demonstrate that cell adhesion is influenced by substrate topography and fibronectin, which mediate the interplay between specific interactions, non-specific interactions, and cell mechanics. Two parallel processes govern the initial adhesion strength: the detachment of the cell body from the substrate and the extraction of tethers from the cell membrane. The duration of the latter process is determined by tether lifetimes, and is a major contributor to the overall work required for cell-substrate detachment. Cell body detachment and tether lifetimes are affected by surface topography and may be strongly modulated by the presence of adsorbed proteins, whereas the tether extraction forces remained unchanged by these factors.

Atomic force microscopy studies of the influence of convex and concave nanostructures on the adsorption of fibronectin.

Atomic force microscopy (AFM)-based force spectroscopy was used to analyze the adsorption of bovine plasma fibronectin on periodically grooved nanostructures (groove/summit width: 90 nm; depth: 120 nm). We present a simple procedure that allowed us to directly compare the local protein density and conformation for the convex summits, the concave grooves and planar reference regions of the substrate. At a bulk fibronectin concentration of 5 µg/ml, the amount of adsorbed protein per surface area was significantly higher in all regions of the nanostructure than on the planar reference, and fibronectin tended to adsorb preferentially in the concave grooves. The increased surface concentration resulted in an additional stabilization of the molecules by protein-protein interactions and a lower degree of denaturized fibronectin in the nanostructured regions. The stabilization was less pronounced in concave regions, indicating that the increased contact area in the grooves counteracted the stabilization by increased protein-substrate interactions and must be compensated for by additional protein-protein interactions. Less favorable sites were occupied at higher bulk fibronectin concentrations (25 µg/ml, 100 µg/ml), and a high degree of native folded fibronectin was observed in both the nanostructured and planar regions. Our results demonstrate that the amount of adsorbed fibronectin per surface area can be increased if a substrate is provided with a topographic nanostructure. Our results also show that the local conformational state of fibronectin is determined by the locally different interplay of protein-protein and protein-substrate interactions.

Electrostatic and dispersion interactions during protein adsorption on topographic nanostructures.

Recently, biomaterials research has focused on developing functional implant surfaces with well-defined topographic nanostructures in order to influence protein adsorption and cellular behavior. To enhance our understanding of how proteins interact with such surfaces, we analyze the adsorption of lysozyme on an oppositely charged nanostructure using a computer simulation. We present an algorithm that combines simulated Brownian dynamics with numerical field calculation methods to predict the preferred adsorption sites for arbitrarily shaped substrates. Either proteins can be immobilized at their initial adsorption sites or surface diffusion can be considered. Interactions are analyzed on the basis of Derjaguin-Landau-Verway-Overbeek (DLVO) theory, including electrostatic and London dispersion forces, and numerical solutions are derived using the Poisson-Boltzmann and Hamaker equations. Our calculations show that for a grooved nanostructure (i.e., groove and plateau width 8 nm, height 4 nm), proteins first contact the substrate primarily near convex edges because of better geometric accessibility and increased electric field strengths. Subsequently, molecules migrate by surface diffusion into grooves and concave corners, where short-range dispersion interactions are maximized. In equilibrium, this mechanism leads to an increased surface protein concentration in the grooves, demonstrating that the total amount of protein per surface area can be increased if substrates have concave nanostructures.

The influence of topographic microstructures on the initial adhesion of L929 fibroblasts studied by single-cell force spectroscopy.

Single-cell force spectroscopy was used to investigate the initial adhesion of L929 fibroblasts onto periodically grooved titanium microstructures (height ~6 µm, groove width 20 µm). The position-dependent local adhesion strength of the cells was correlated with their rheological behavior. Spherical cells exhibited a significantly lower Young's modulus (<1 kPa) than that reported for spread cells, and their elastic properties can roughly be explained by the Hertz model for an elastic sphere. While in contact with the planar regions of the substrate, the cells started to adapt their shape through slight ventral flattening. The process was found to be independent of the applied contact force for values between 100 and 1,000 pN. The degree of flattening correlated with the adhesion strength during the first 60 s. Adhesion strength can be described by fast exponential kinetics as C1[1-exp(-C2·t] with C1 = 2.34 ± 0.19 nN and C2 = 0.09 ± 0.02 s⁻¹. A significant drop in the adhesion strength of up to 50% was found near the groove edges. The effect can be interpreted by the geometric decrease of the contact area, which indicates the inability of the fibroblasts to adapt to the shape of the substrate. Our results explain the role of the substrate's topography in contact guidance and suggest that rheological cell properties must be considered in cell adhesion modeling.

Mechanical integrin stress and magnetic forces induce biological responses in mesenchymal stem cells which depend on environmental factors.

The control of mesenchymal stem cells (MSC) by physical cues is of great interest in regenerative medicine. Because integrin receptors function as mechanotransducers, we applied drag forces to ß1 integrins on the apical surface of adherent human MSC. In addition to mechanical forces, the technique we used involved also the exposure of the cells to an inhomogeneous magnetic field. In order to assess the influence of the substrate on cell adhesion, cells were cultured on plain tissue culture polystyrene (TCP) or on coated well plates, which allowed only adhesion to embedded fibronectin or RGD peptides. We found that the expression of collagen I, which is involved in osteogenesis, and VEGF, a factor which stimulates angiogenesis, increased as a result of short-term mechanical integrin stress. Whereas, collagen I expression was stimulated by mechanical forces when the cells were cultured on fibronectin and RGD peptides but not on TCP, VEGF expression was enhanced by physical stimulation on TCP. The study further revealed that magnetic forces enhanced Sox 9 expression, a marker of chondrogenesis, and reduced the expression of ALP. Concerning the intracellular mechanisms involved, we found that the expression of VEGF induced by physical forces depended on Akt activation. Together, the results implicate that biological functions of MSC can be stimulated by integrin-mediated mechanical forces and a magnetic field. However, the responses of cells depend strongly on the substrate to which they adhere and on the cross-talk between integrin-mediated signals and soluble factors.

Varieties of second modernity: the cosmopolitan turn in social and political theory and research.

The theme of this special issue is the necessity of a cosmopolitan turn in social and political theory. The question at the heart of this introductory chapter takes the challenge of 'methodological cosmopolitanism', already addressed in a Special Issue on Cosmopolitan Sociology in this journal (Beck and Sznaider 2006), an important step further: How can social and political theory be opened up, theoretically as well as methodologically and normatively, to a historically new, entangled Modernity which threatens its own foundations? How can it account for the fundamental fragility, the mutability of societal dynamics (of unintended side effects, domination and power), shaped by the globalization of capital and risks at the beginning of the twenty-first century? What theoretical and methodological problems arise and how can they be addressed in empirical research? In the following, we will develop this 'cosmopolitan turn' in four steps: firstly, we present the major conceptual tools for a theory of cosmopolitan modernities; secondly, we de-construct Western modernity by using examples taken from research on individualization and risk; thirdly, we address the key problem of methodological cosmopolitanism, namely the problem of defining the appropriate unit of analysis; and finally,we discuss normative questions, perspectives, and dilemmas of a theory of cosmopolitan modernities, in particular problems of political agency and prospects of political realization.

Preparation, microstructures, mechanical properties, and cytocompatibility of TiMn alloys for biomedical applications.

The titanium-manganese (TiMn) alloys have been extensively used in aerospace and hydrogen storage. In this study, the TiMn alloys with various manganese contents ranging from 2 to 12 wt % were prepared by using mechanical alloying and spark plasma sintering (SPS) techniques. The microstructures, mechanical properties including hardness, elastic modulus and ductility, cytotoxicity and cell proliferation properties of the TiMn alloys were investigated to explore their biomedical applications. The addition of manganese to the titanium reduced the alpha to beta transformation temperature and was confirmed as a beta stabilizer element. The manganese increased the relative density of the alloy and thus high density TiMn alloys with alpha+beta structure were prepared by using SPS at 700 degrees C. The hardness increased significantly ranging from 2.4 GPa (Ti2Mn) to 5.28 GPa (Ti12Mn) and the elastic modulus ranging from 83.3 GPa (Ti2Mn) to 122 GPa (Ti12Mn), the ductility decreased ranging from 21.3% (Ti2Mn) to 11.7% (Ti12Mn) with increasing manganese content in the Ti. Concentrations of Mn below 8 wt % in titanium reveal negligible effects on the metabolic activity and the cell proliferation of human osteoblasts. The Mn could be used in lower concentrations as an alloying element for biomedical titanium. The Ti2Mn, Ti5Mn, and Ti8Mn alloys with supervisor mechanical properties and acceptable cytocompatibility have a potential for use as bone substitutes and dental implants.

Cell architecture-cell function dependencies on titanium arrays with regular geometry.

Knowledge about biocomplexity of cell behavior in dependence on topographical characteristics is of clinical relevance for the development of implant designs in tissue engineering. The aim of this study was to find out cell architecture-cell function dependencies of human MG-63 osteoblasts on titanium (Ti) arrays with regular geometry. We compared cubic pillar structures (SU-8, dimension 3 x 3 x 5 and 5 x 5 x 5 mum) with planar samples. Electrochemical surface characterization revealed a low amount of surface energy (including polar component) for the pillar-structured surfaces, which correlated with a reduced initial cell adhesion and spreading. Confocal microscopy of cell's actin cytoskeleton revealed no stress fiber organization instead, the actin was concentrated in a surface geometry-dependent manner as local spots around the pillar edges. This altered cell architecture resulted in an impaired MG-63 cell function - the extracellular matrix proteins collagen-I and bone sialo protein (BSP-2) were synthesized at a significantly lower level on SU-8 pillar structures; this was accompanied by reduced beta3-integrin expression. To find out physicochemical factors pertaining to geometrically microstructured surfaces and their influence on adjoining biosystems is important for the development of biorelevant implant surfaces.

A novel modular device for 3-D bone cell culture and non-destructive cell analysis.

Synthetic materials have emerged as bone substitutes for filling bone defects of critical sizes. Because bone healing requires a mechanically resistant matrix (scaffold) attractive to osteogenic cells and must allow revascularization for nutrient and oxygen supply, scaffold-based strategies focus on the further development of chemical and physical qualities of the material. Cellular ingrowth towards the scaffold center is critical; therefore selective information from inner regions, in particular from the central part, is essential. In this paper we introduce a novel modular in vitro system for three-dimensional (3-D) in vitro bone cell cultures. This 3-D system is developed exclusively for in vitro research purposes, with special emphasis on the geometrical scaffold design (pore size, pore design). The system is composed of a stack of titanium slices which are mounted on a clamp and which enable the separate monitoring of cell growth patterns on every single slice of the slide stack. In this way we are able to gain selective information about the regulation of the cell physiology in the inner part of the 3-D construct which can be used for the development of an optimized scaffold design for orthopedic implants.

Unpacking cosmopolitanism for the social sciences: a research agenda. 2006.

This article calls for a re-conceptualization of the social sciences by asking for a cosmopolitan turn. The intellectual undertaking of redefining cosmopolitanism is a trans-disciplinary one, which includes geography, anthropology, ethnology, international relations, international law, political philosophy and political theory, and now sociology and social theory. Methodological nationalism, which subsumes society under the nation-state, has until now made this task almost impossible. The alternative, a 'cosmopolitan outlook', is a contested term and project. Cosmopolitanism must not be equalized with the global (or globalization), with 'world system theory' (Wallerstein), with 'world polity' (Meyer and others), or with 'world-society' (Luhmann). All of those concepts presuppose basic dualisms, such as domestic/foreign or national/international, which in reality have become ambiguous. Methodological cosmopolitanism opens up new horizons by demonstrating how we can make the empirical investigation of border crossings and other transnational phenomena possible.

Beyond class and nation: reframing social inequalities in a globalizing world.

From the start individualization theory is the investigation of the paradigm shift in social inequality. Furthermore it shows, how the transnationalization of social inequalities bursts the framework of institutional responses - nation state (parties), trade unions, welfare state systems and the national sociologies of social classes. In this essay I shall try to conceptually elucidate the 'cosmopolitan perspective' on relations of social inequality in three cases: (1) the inequality of global risk; (2) the Europe-wide dynamic of inequality; and (3) transnational inequalities, which emerge from the capacities and resources to transcend borders. Before that I take up Will Atkinson's question: 'What exactly constitutes individualization and to what extent has it really displaced class?' (Atkinson 2007: Abstract).

Interface interactions of osteoblasts with structured titanium and the correlation between physicochemical characteristics and cell biological parameters.

Cellular behavior at the interface of an implant is influenced by the material's topography. However, little is known about the correlation between the biological parameters and the physicochemical characteristics of the biomaterial. We therefore modified pure titanium surfaces by polishing, machining, blasting with glass spheres, blasting with corundum particles, and vacuum plasma spraying to give progressively higher surface roughness. The material surface was characterized by SEM, surface profiling, and electrochemical methods. We revealed a correlation for integrin expression and formation, adhesion, spreading, proliferation, and bone sialo protein expression with the physicochemical parameters of the titanium surfaces.

Unpacking cosmopolitanism for the social sciences: a research agenda.

This article calls for a re-conceptualization of the social sciences by asking for a cosmopolitan turn. The intellectual undertaking of redefining cosmopolitanism is a trans-disciplinary one, which includes geography, anthropology, ethnology, international relations, international law, political philosophy and political theory, and now sociology and social theory. Methodological nationalism, which subsumes society under the nation-state, has until now made this task almost impossible. The alternative, a 'cosmopolitan outlook', is a contested term and project. Cosmopolitanism must not be equalized with the global (or globalization), with 'world system theory' (Wallerstein), with 'world polity' (Meyer and others), or with 'world-society' (Luhmann). All of those concepts presuppose basic dualisms, such as domestic/foreign or national/international, which in reality have become ambiguous. Methodological cosmopolitanism opens up new horizons by demonstrating how we can make the empirical investigation of border crossings and other transnational phenomena possible.

Second modernity as a research agenda: theoretical and empirical explorations in the 'meta-change' of modern society.

In this article we are reformulating the theory of reflexive modernization as an empirical research programme and summarize some of the most recent findings which have been produced by a research consortium in Munich (integrating four universities, funded by the German Research Society (DFG)). On this basis we reject the idea that Western societies at the beginning of the twenty-first century move from the modern to the post-modern. We argue that there has been no clear break with the basic principles of modernity but rather a transformation of basic institutions of modernity such as the nation-state and the nuclear family. We would suggest, therefore, that what we are witnessing is a second modernity. Finally, we reform the theory of reflexive modernization in reaction to three uttered objections.

How not to become a museum piece.

In this essay I want to address two question marks which arose during my reading of Michael Burawoy's inspiring piece. First, sharing his spirit of recreating the sociological enlightenment by differentiating between different types of public sociologies, I do not share his optimism that sociology can easily become an integral part of public discourse and practice. Second, I don't think that mainstream sociology is really prepared for this adventure. My argument points in the opposite direction: all the different forms of public and non-public sociology are in danger of becoming museum pieces. Thus, sociology not only needs a public voice, it also needs to be reinvented first--in order to have a public voice at all!

Control of focal adhesion dynamics by material surface characteristics.

The mechanisms of cell adhesion to the extracellular matrix (ECM) which are of fundamental importance for function, survival, and growth of cells involve the formation of focal adhesions to facilitate integrin signaling. Recently, it became evident that focal adhesions are not stable but move to enable cell migration and ECM formation. We examined the number, size, and dynamic behavior of focal adhesions in living MG-63 osteoblastic cells, which were cultured on titanium surfaces with different roughnesses and on stainless steel (SS). As a marker for focal adhesions we used GFP-tagged vinculin, a cytoskeletal protein. Focal adhesions were smaller on titanium and on SS than on collagen-coated glass coverslips. The corundum-blasted rough surface of titanium induced the smallest adhesions. On all the surfaces that we have tested, we observed a mobility of focal adhesions. On collagen-coated coverslips focal adhesions moved with a speed of 60 nm/min. The speed was reduced on titanium and still more restricted on SS. The topography did not affect the mobility of focal adhesions. We conclude that on the material surfaces that we have studied a reduced mobility of focal adhesions may strengthen the linkages between cell and ECM but impair the ability to dynamically organize and remodel the ECM. The results may have a great impact in the functional evaluation of tailored biomaterial surfaces for the application in tissue engineering.

The influence of surface roughness of titanium on beta1- and beta3-integrin adhesion and the organization of fibronectin in human osteoblastic cells.

Mechanisms of cell adhesion and extracellular matrix formation are primary processes in the interaction with the material surface of an implant which are controlled by integrin receptors. The aim of our study was to find out whether beta1- and beta3-integrins of osteoblastic cells sense the surface topography of titanium, and if structural alterations of integrin adhesions were involved in the organization of fibronectin. Pure titanium surfaces were modified by polishing (P), machining (NT), blasting with glass spheres (GB), and blasting with corundum particles (CB) resulting in increasing roughness. Confocal microscopic investigations revealed fibrillar adhesions of beta1- and alpha5-integrins on P, NT, and GB, but on CB with its sharp edges these integrin subunits did not form fibrillar adhesions. beta3 generally appeared in focal adhesions. We observed aligned fibrillar structures of fibronectin on NT not only on the basal site but interestingly, also on the apical cell surface. In contrast, on CB, fibronectin appeared apically clustered. We suggest that this alignment of fibronectin fibrils depends on the directed actin cytoskeleton and in particular, on the capability of the beta1-integrins to form fibrillar adhesions, which is affected by the surface roughness of titanium.