OR.NET - Approaches for Risk Analysis and Measures of Dynamically Interconnected Medical Devices

Nowadays, it lacks an open, standardized and dynamic interconnection of medical devices. All existing combinations of medical devices consist of isolated solutions with proprietary interfaces, as no common standards for networking and the exchange of data of medical devices exist. This situation leads to confusing operating rooms and inefficient operations. Thus, new strategies need to be developed for the authorization of dynamically interconnected medical devices. Primarily, those concern of an acquisition and methodical adaption of new requirements and risks resulting from this way of interconnection. The approach is to develop a method for a risk analysis for interconnected medical devices, which is structured modular and consists of a risk assessment of the standalone device and a risk analysis for the interconnection considering the risks involved in the transfer of functions. When interconnecting the medical devices the risk analysis of each of the devices is taken and they are compared by a gap analysis. Through this strategy it will be possible to realize a standard-compliant dynamic interconnection of medical products, which would be advantageous both for clinic operators and producers. This paper presents the current situation of the authorization of combined medical devices and proposes a strategy for the risk management of dynamically interconnected medical devices as a substantial part of the authorization

Development and Function of Dendritic Cell Subsets

Classical dendritic cells (cDCs) form a critical interface between innate and adaptive immunity. As myeloid immune cell sentinels, cDCs are specialized in the sensing of pathogen challenges and cancer. They translate the latter for T cells into peptide form. Moreover, cDCs provide additional critical information on the original antigen context to trigger a diverse spectrum of appropriate protective responses. Here we review recent progress in our understanding of cDC subsets in mice. We will discuss cDC subset ontogeny and transcription factor dependencies, as well as emerging functional specializations within the cDC compartment in lymphoid and nonlymphoid tissues

Global Economic Governance - das Management der Weltwirtschaft ein Jahr nach dem G-8-Gipfel von Heiligendamm

Am 11. und 12. Juli 2008 fand unter der Leitung von Saskia Hieber und Wolfgang Quaisser, Akademie für Politische Bildung Tutzing, sowie Stefan A. Schirm, Ruhr-Universität Bochum, die Tagung »Global Economic Governance – das Management der Weltwirtschaft ein Jahr nach dem G-8-Gipfel von Heiligendamm« statt. Die Veranstaltung nahm ein Jahr nach dem G-8-Gipfel die Diskussion um ein besseres Management der Weltwirtschaft wieder auf und fragte – nach einer Bestandsaufnahme der Globalisierung der Finanzmärkte und des Welthandels – nach Möglichkeiten für ihre Governance durch die Staatengemeinschaft. Im Vordergrund standen die Analyse der Chancen und Risiken internationaler Handels- und Kapitalbewegungen, ihre Auswirkungen auf nationale Gesellschaften und die Strategien für ein effizienteres, aber auch legitimeres Management durch internationale Organisationen. Zur Einführung in das Thema unterstrich Stefan A. Schirm, Universität Bochum, die Notwendigkeit, bei der Analyse der Global-Economic-Governance-Debatte nach den handelnden Akteuren und ihren spezifischen Motiven zu suchen. Martin Hüfner, HF Economics Ltd., analysierte Chancen und Risiken globaler Finanzmärkte, Karlhans Sauernheimer, Universität Mainz, die Chancen und Risiken einer Liberalisierung des Welthandels. Alexander Lau, Deutscher Industrie- und Handelskammertag, befasste sich mit dem Erfolg der deutschen Unternehmen im Ausland und zeigte, dass der Standort Deutschland vom zunehmenden Auslandsengagement der deutschen Unternehmen profitiert. Isabella Timm-Guri, Bayerischer Bauernverband, stellte die Auswirkungen der Handelsliberalisierung auf die europäische Agrarwirtschaft und ihre Anliegen für die Gestaltung internationaler Handelsregeln dar. Stormy Mildner, Stiftung Wissenschaft und Politik, stellte die Gründe vor, die aus ihrer Sicht zum Scheitern der Doha-Runde führten. Und Laura Carsten, Universität Bochum, analysierte den Einfluss der Schwellenländer auf den IWF und die WTO.

IκB kinase 2 determines oligodendrocyte loss by non-cell-autonomous activation of NF-κB in the central nervous system

The IκB kinase complex induces nuclear factor kappa B activation and has recently been recognized as a key player of autoimmunity in the central nervous system. Notably, IκB kinase/nuclear factor kappa B signalling regulates peripheral myelin formation by Schwann cells, however, its role in myelin formation in the central nervous system during health and disease is largely unknown. Surprisingly, we found that brain-specific IκB kinase 2 expression is dispensable for proper myelin assembly and repair in the central nervous system, but instead plays a fundamental role for the loss of myelin in the cuprizone model. During toxic demyelination, inhibition of nuclear factor kappa B activation by conditional ablation of IκB kinase 2 resulted in strong preservation of central nervous system myelin, reduced expression of proinflammatory mediators and a significantly attenuated glial response. Importantly, IκB kinase 2 depletion in astrocytes, but not in oligodendrocytes, was sufficient to protect mice from myelin loss. Our results reveal a crucial role of glial cell-specific IκB kinase 2/nuclear factor kappa B signalling for oligodendrocyte damage during toxic demyelination. Thus, therapies targeting IκB kinase 2 function in non-neuronal cells may represent a promising strategy for the treatment of distinct demyelinating central nervous system disease

Transcriptional Reprogramming of CD11b+Esamhi Dendritic Cell Identity and Function by Loss of Runx3

Classical dendritic cells (cDC) are specialized antigen-presenting cells mediating immunity and tolerance. cDC cell-lineage decisions are largely controlled by transcriptional factor regulatory cascades. Using an in vivo cell-specific targeting of Runx3 at various stages of DC lineage development we show that Runx3 is required for cell-identity, homeostasis and function of splenic Esamhi DC. Ablation of Runx3 in DC progenitors led to a substantial decrease in splenic CD4+/CD11b+ DC. Combined chromatin immunoprecipitation sequencing and gene expression analysis of purified DC-subsets revealed that Runx3 is a key gene expression regulator that facilitates specification and homeostasis of CD11b+Esamhi DC. Mechanistically, loss of Runx3 alters Esamhi DC gene expression to a signature characteristic of WT Esamlow DC. This transcriptional reprogramming caused a cellular change that diminished phagocytosis and hampered Runx3-/- Esamhi DC capacity to prime CD4+ T cells, attesting to the significant role of Runx3 in specifying Esamhi DC identity and function

Tongue immune compartment analysis reveals spatial macrophage heterogeneity

The tongue is a unique muscular organ situated in the oral cavity where it is involved in taste sensation, mastication, and articulation. As a barrier organ, which is constantly exposed to environmental pathogens, the tongue is expected to host an immune cell network ensuring local immune defence. However, the composition and the transcriptional landscape of the tongue immune system are currently not completely defined. Here, we characterised the tissue-resident immune compartment of the murine tongue during development, health and disease, combining single-cell RNA-sequencing with in situ immunophenotyping. We identified distinct local immune cell populations and described two specific subsets of tongue-resident macrophages occupying discrete anatomical niches. Cx3cr1(+) macrophages were located specifically in the highly innervated lamina propria beneath the tongue epidermis and at times in close proximity to fungiform papillae. Folr2(+) macrophages were detected in deeper muscular tissue. In silico analysis indicated that the two macrophage subsets originate from a common proliferative precursor during early postnatal development and responded differently to systemic LPS in vivo. Our description of the under-investigated tongue immune system sets a starting point to facilitate research on tongue immune-physiology and pathology including cancer and taste disorders

Smad7 in T cells drives T helper 1 responses in multiple sclerosis and experimental autoimmune encephalomyelitis

Autoreactive CD4+ T lymphocytes play a vital role in the pathogenesis of multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis. Since the discovery of T helper 17 cells, there is an ongoing debate whether T helper 1, T helper 17 or both subtypes of T lymphocytes are important for the initiation of autoimmune neuroinflammation. We examined peripheral blood CD4+ cells from patients with active and stable relapsing–remitting multiple sclerosis, and used mice with conditional deletion or over-expression of the transforming growth factor-β inhibitor Smad7, to delineate the role of Smad7 in T cell differentiation and autoimmune neuroinflammation. We found that Smad7 is up-regulated in peripheral CD4+ cells from patients with multiple sclerosis during relapse but not remission, and that expression of Smad7 strongly correlates with T-bet, a transcription factor defining T helper 1 responses. Concordantly, mice with transgenic over-expression of Smad7 in T cells developed an enhanced disease course during experimental autoimmune encephalomyelitis, accompanied by elevated infiltration of inflammatory cells and T helper 1 responses in the central nervous system. On the contrary, mice with a T cell-specific deletion of Smad7 had reduced disease and central nervous system inflammation. Lack of Smad7 in T cells blunted T cell proliferation and T helper 1 responses in the periphery but left T helper 17 responses unaltered. Furthermore, frequencies of regulatory T cells were increased in the central nervous system of mice with a T cell-specific deletion and reduced in mice with a T cell-specific over-expression of Smad7. Downstream effects of transforming growth factor-β on in vitro differentiation of naïve T cells to T helper 1, T helper 17 and regulatory T cell phenotypes were enhanced in T cells lacking Smad7. Finally, Smad7 was induced during T helper 1 differentiation and inhibited during T helper 17 differentiation. Taken together, the level of Smad7 in T cells determines T helper 1 polarization and regulates inflammatory cellular responses. Since a Smad7 deletion in T cells leads to immunosuppression, Smad7 may be a potential new therapeutic target in multiple sclerosis

The fate and lifespan of human monocyte subsets in steady state and systemic inflammation.

In humans, the monocyte pool comprises three subsets (classical, intermediate, and nonclassical) that circulate in dynamic equilibrium. The kinetics underlying their generation, differentiation, and disappearance are critical to understanding both steady-state homeostasis and inflammatory responses. Here, using human in vivo deuterium labeling, we demonstrate that classical monocytes emerge first from marrow, after a postmitotic interval of 1.6 d, and circulate for a day. Subsequent labeling of intermediate and nonclassical monocytes is consistent with a model of sequential transition. Intermediate and nonclassical monocytes have longer circulating lifespans (∼4 and ∼7 d, respectively). In a human experimental endotoxemia model, a transient but profound monocytopenia was observed; restoration of circulating monocytes was achieved by the early release of classical monocytes from bone marrow. The sequence of repopulation recapitulated the order of maturation in healthy homeostasis. This developmental relationship between monocyte subsets was verified by fate mapping grafted human classical monocytes into humanized mice, which were able to differentiate sequentially into intermediate and nonclassical cells

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis

Bose-Einstein correlations of charged hadrons in proton-proton collisions at s\sqrt s = 13 TeV

Bose-Einstein correlations of charged hadrons are measured over a broad multiplicity range, from a few particles up to about 250 reconstructed charged hadrons in proton-proton collisions at $\sqrt{s}$ = 13 TeV. The results are based on data collected using the CMS detector at the LHC during runs with a special low-pileup configuration. Three analysis techniques with different degrees of dependence on simulations are used to remove the non-Bose-Einstein background from the correlation functions. All three methods give consistent results. The measured lengths of homogeneity are studied as functions of particle multiplicity as well as average pair transverse momentum and mass. The results are compared with data from both CMS and ATLAS at $\sqrt{s}$ = 7 TeV, as well as with theoretical predictions.[graphic not available: see fulltext]Bose-Einstein correlations of charged hadrons are measured over a broad multiplicity range, from a few particles up to about 250 reconstructed charged hadrons in proton-proton collisions at $\sqrt{s} =$ 13 TeV. The results are based on data collected using the CMS detector at the LHC during runs with a special low-pileup configuration. Three analysis techniques with different degrees of dependence on simulations are used to remove the non-Bose-Einstein background from the correlation functions. All three methods give consistent results. The measured lengths of homogeneity are studied as functions of particle multiplicity as well as average pair transverse momentum and mass. The results are compared with data from both CMS and ATLAS at $\sqrt{s} =$ 7 TeV, as well as with theoretical predictions