Incidence and Imaging Outcomes of Acute Scaffold Disruption and Late Structural Discontinuity After Implantation of the Absorb Everolimus-Eluting Fully Bioresorbable Vascular Scaffold: Optical Coherence Tomography Assessment in the ABSORB Cohort B Trial (A Clinical Evaluation of the Bioabsorbable Everolimus Eluting Coronary Stent System in the Treatment of Patients With De Novo Native Coronary Artery Lesions).

OBJECTIVES This study sought to describe the frequency and clinical impact of acute scaffold disruption and late strut discontinuity of the second-generation Absorb bioresorbable polymeric vascular scaffolds (Absorb BVS, Abbott Vascular, Santa Clara, California) in the ABSORB (A Clinical Evaluation of the Bioabsorbable Everolimus Eluting Coronary Stent System in the Treatment of Patients With De Novo Native Coronary Artery Lesions) cohort B study by optical coherence tomography (OCT) post-procedure and at 6, 12, 24, and 36 months. BACKGROUND Fully bioresorbable scaffolds are a novel approach to treatment for coronary narrowing that provides transient vessel support with drug delivery capability without the long-term limitations of metallic drug-eluting stents. However, a potential drawback of the bioresorbable scaffold is the potential for disruption of the strut network when overexpanded. Conversely, the structural discontinuity of the polymeric struts at a late stage is a biologically programmed fate of the scaffold during the course of bioresorption. METHODS The ABSORB cohort B trial is a multicenter single-arm trial assessing the safety and performance of the Absorb BVS in the treatment of 101 patients with de novo native coronary artery lesions. The current analysis included 51 patients with 143 OCT pullbacks who underwent OCT at baseline and follow-up. The presence of acute disruption or late discontinuities was diagnosed by the presence on OCT of stacked, overhung struts or isolated intraluminal struts disconnected from the expected circularity of the device. RESULTS Of 51 patients with OCT imaging post-procedure, acute scaffold disruption was observed in 2 patients (3.9%), which could be related to overexpansion of the scaffold at the time of implantation. One patient had a target lesion revascularization that was presumably related to the disruption. Of 49 patients without acute disruption, late discontinuities were observed in 21 patients. There were no major adverse cardiac events associated with this finding except for 1 patient who had a non-ischemia-driven target lesion revascularization. CONCLUSIONS Acute scaffold disruption is a rare iatrogenic phenomenon that has been anecdotally associated with anginal symptoms, whereas late strut discontinuity is observed in approximately 40% of patients and could be viewed as a serendipitous OCT finding of a normal bioresorption process without clinical implications. (ABSORB Clinical Investigation, Cohort B [ABSORB B]; NCT00856856).

The structural substrate of brain function: analysis of brain structural networks based on diffusion-weighted imaging

The brain is a complex neural network with a hierarchical organization and the mapping of its elements and connections is an important step towards the understanding of its function. Recent developments in diffusion-weighted imaging have provided the opportunity to reconstruct the whole-brain structural network in-vivo at a large scale level and to study the brain structural substrate in a framework that is close to the current understanding of brain function. However, methods to construct the connectome are still under development and they should be carefully evaluated. To this end, the first two studies included in my thesis aimed at improving the analytical tools specific to the methodology of brain structural networks. The first of these papers assessed the repeatability of the most common global and local network metrics used in literature to characterize the connectome, while in the second paper the validity of further metrics based on the concept of communicability was evaluated. Communicability is a broader measure of connectivity which accounts also for parallel and indirect connections. These additional paths may be important for reorganizational mechanisms in the presence of lesions as well as to enhance integration in the network. These studies showed good to excellent repeatability of global network metrics when the same methodological pipeline was applied, but more variability was detected when considering local network metrics or when using different thresholding strategies. In addition, communicability metrics have been found to add some insight into the integration properties of the network by detecting subsets of nodes that were highly interconnected or vulnerable to lesions. The other two studies used methods based on diffusion-weighted imaging to obtain knowledge concerning the relationship between functional and structural connectivity and about the etiology of schizophrenia. The third study integrated functional oscillations measured using electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) as well as diffusion-weighted imaging data. The multimodal approach that was applied revealed a positive relationship between individual fluctuations of the EEG alpha-frequency and diffusion properties of specific connections of two resting-state networks. Finally, in the fourth study diffusion-weighted imaging was used to probe for a relationship between the underlying white matter tissue structure and season of birth in schizophrenia patients. The results are in line with the neurodevelopmental hypothesis of early pathological mechanisms as the origin of schizophrenia. The different analytical approaches selected in these studies also provide arguments for discussion of the current limitations in the analysis of brain structural networks. To sum up, the first studies presented in this thesis illustrated the potential of brain structural network analysis to provide useful information on features of brain functional segregation and integration using reliable network metrics. In the other two studies alternative approaches were presented. The common discussion of the four studies enabled us to highlight the benefits and possibilities for the analysis of the connectome as well as some current limitations.

Deficit actual tool use in schizophrenia is linked to structural alterations in key regions of planning and executing of tool use and connecting fibers

Introduction: Schizophrenia patients frequently suffer from complex motor abnormalities including fine and gross motor disturbances, abnormal involuntary movements, neurological soft signs and parkinsonism. These symptoms occur early in the course of the disease, continue in chronic patients and may deteriorate with antipsychotic medication. Furthermore gesture performance is impaired in patients, including the pantomime of tool use. Whether schizophrenia patients would show difficulties of actual tool use has not yet been investigated. Human tool use is complex and relies on a network of distinct and distant brain areas. We therefore aim to test if schizophrenia patients had difficulties in tool use and to assess associations with structural brain imaging using voxel based morphometry (VBM) and tract based spatial statistics (TBSS). Methode: In total, 44 patients with schizophrenia (DSM-5 criteria; 59% men, mean age 38) underwent structural MR imaging and performed the Tool-Use test. The test examines the use of a scoop and a hammer in three conditions: pantomime (without the tool), demonstration (with the tool) and actual use (with a recipient object). T1-weighted images were processed using SPM8 and DTI-data using FSL TBSS routines. To assess structural alterations of impaired tool use we first compared gray matter (GM) volume in VBM and white matter (WM) integrity in TBSS data of patients with and without difficulties of actual tool use. Next we explored correlations of Tool use scores and VBM and TBSS data. Group comparisons were family wise error corrected for multiple tests. Correlations were uncorrected (p < 0.001) with a minimum cluster threshold of 17 voxels (equivalent to a map-wise false positive rate of alpha < 0.0001 using a Monte Carlo procedure). Results: Tool use was impaired in schizophrenia (43.2% pantomime, 11.6% demonstration, 11.6% use). Impairment was related to reduced GM volume and WM integrity. Whole brain analyses detected an effect in the SMA in group analysis. Correlations of tool use scores and brain structure revealed alterations in brain areas of the dorso-dorsal pathway (superior occipital gyrus, superior parietal lobule, and dorsal premotor area) and the ventro-dorsal pathways (middle occipital gyrus, inferior parietal lobule) the action network, as well as the insula and the left hippocampus. Furthermore, significant correlations within connecting fiber tracts - particularly alterations within the bilateral corona radiata superior and anterior as well as the corpus callosum -were associated with Tool use performance. Conclusions: Tool use performance was impaired in schizophrenia, which was associated with reduced GM volume in the action network. Our results are in line with reports of impaired tool use in patients with brain lesions particularly of the dorso-dorsal and ventro-dorsal stream of the action network. In addition an effect of tool use on WM integrity was shown within fiber tracts connecting regions important for planning and executing tool use. Furthermore, hippocampus is part of a brain system responsible for spatial memory and navigation.The results suggest that structural brain alterations in the common praxis network contribute to impaired tool use in schizophrenia.

Possibilities of fertility preservation in young patients with ovarian cancer

BACKGROUND Ovarian cancer is a rare disease especially in young patients and surgical treatment often leads to loss of fertility. This study investigated the incidence of the different histological types and discusses the possibility of fertility preservation. PATIENTS AND METHODS A retrospective analysis of patients with an ovarian tumour under the age of 40 who presented either to the Women's University Hospital, Tuebingen or to centres of the FertiPROTEKT network was performed. RESULTS Out of 51 patients with ovarian cancer from Tuebingen, 21 (41.2%) were eligible for fertility-preserving surgery, 11 received chemotherapy and from those 4 (36.4%) chose a fertility preservation technique. From the FertiPROTEKT network, 26/41 patients (63.4%) decided to undergo fertility preservation. No complications and postponement of chemotherapy due to fertility preservation procedures were noted. CONCLUSION With careful consideration of the risks, the correct indication and diligent aftercare, the realisation of conception is possible also for patients with ovarian cancer.

Legal Aspects of Sino-­African Tied Aid: The Art of Playing with a Legal Grey Area

Sino-African trade has seen a fifty-fold increase in the years 1999 to 2008. In some African regions, particularly in sub-Saharan Africa, China has even replaced the US as the most important trading partner today. But China holds not a single FTA on the African continent, while other major trading partners of African economies rely on an extensive framework of different trade agreements. What is, thus, the legal basis of the recent increase of Sino-African trade? Interestingly, Sino-African trade has seen a particularly strong increase in countries that have entered into tied aid agreements with China. These agreements are commonly known under the term ‘Angola-Model’ and consist of a multifaceted network of barter-trading-systems, aspects of tied aid and concessions for oil and other commodities linked with a state loan. It is likely that these agreements have an impact on the trade-flows between African countries and China. This paper discusses the legal character of this new form of economic cooperation, or modern version of tied aid. Critical legal aspects related to this form of tied aid refer to violation of the principle of most-favoured nation (MFN), illegitimate export subsidies, market access, public procurement and transparency in the international trading system. However, despite the recent outcry of the foremost Western community against the strategy of the Chinese government on the African continent, the practice of the Angola-Model based tied aid is not entirely new, and neither is it against the law. The case of tied aid is situated in a legal grey area that should be examined thoroughly in order to strengthen the international trading system and to support developing countries in their attempt to gain from tied aid arrangements.

A Tutorial of the Mobile Multimedia Wireless Sensor Network (M3WSN) OMNeT++ Framework

In this work, we will give a detailed tutorial instruction about how to use the Mobile Multi-Media Wireless Sensor Networks (M3WSN) simulation framework. The M3WSN framework has been published as a scientific paper in the 6th International Workshop on OMNeT++ (2013) [1]. M3WSN framework enables the multimedia transmission of real video se- quence. Therefore, a set of multimedia algorithms, protocols, and services can be evaluated by using QoE metrics. Moreover, key video-related information, such as frame types, GoP length and intra-frame dependency can be used for creating new assessment and optimization solutions. To support mobility, M3WSN utilizes different mobility traces to enable the understanding of how the network behaves under mobile situations. This tutorial will cover how to install and configure the M3WSN framework, setting and running the experiments, creating mobility and video traces, and how to evaluate the performance of different protocols. The tutorial will be given in an environment of Ubuntu 12.04 LTS and OMNeT++ 4.2.

Content-Aware Delivery of Scalable Video in Network Coding Enabled Named Data Networks

In this work, we propose a novel network coding enabled NDN architecture for the delivery of scalable video. Our scheme utilizes network coding in order to address the problem that arises in the original NDN protocol, where optimal use of the bandwidth and caching resources necessitates the coordination of the forwarding decisions. To optimize the performance of the proposed network coding based NDN protocol and render it appropriate for transmission of scalable video, we devise a novel rate allocation algorithm that decides on the optimal rates of Interest messages sent by clients and intermediate nodes. This algorithm guarantees that the achieved flow of Data objects will maximize the average quality of the video delivered to the client population. To support the handling of Interest messages and Data objects when intermediate nodes perform network coding, we modify the standard NDN protocol and introduce the use of Bloom filters, which store efficiently additional information about the Interest messages and Data objects. The proposed architecture is evaluated for transmission of scalable video over PlanetLab topologies. The evaluation shows that the proposed scheme performs very close to the optimal performance

Service level agreements-driven management of distributed applications in cloud computing environments

Advancements in cloud computing have enabled the proliferation of distributed applications, which require management and control of multiple services. However, without an efficient mechanism for scaling services in response to changing workload conditions, such as number of connected users, application performance might suffer, leading to violations of Service Level Agreements (SLA) and possible inefficient use of hardware resources. Combining dynamic application requirements with the increased use of virtualised computing resources creates a challenging resource Management context for application and cloud-infrastructure owners. In such complex environments, business entities use SLAs as a means for specifying quantitative and qualitative requirements of services. There are several challenges in running distributed enterprise applications in cloud environments, ranging from the instantiation of service VMs in the correct order using an adequate quantity of computing resources, to adapting the number of running services in response to varying external loads, such as number of users. The application owner is interested in finding the optimum amount of computing and network resources to use for ensuring that the performance requirements of all her/his applications are met. She/he is also interested in appropriately scaling the distributed services so that application performance guarantees are maintained even under dynamic workload conditions. Similarly, the infrastructure Providers are interested in optimally provisioning the virtual resources onto the available physical infrastructure so that her/his operational costs are minimized, while maximizing the performance of tenants’ applications. Motivated by the complexities associated with the management and scaling of distributed applications, while satisfying multiple objectives (related to both consumers and providers of cloud resources), this thesis proposes a cloud resource management platform able to dynamically provision and coordinate the various lifecycle actions on both virtual and physical cloud resources using semantically enriched SLAs. The system focuses on dynamic sizing (scaling) of virtual infrastructures composed of virtual machines (VM) bounded application services. We describe several algorithms for adapting the number of VMs allocated to the distributed application in response to changing workload conditions, based on SLA-defined performance guarantees. We also present a framework for dynamic composition of scaling rules for distributed service, which used benchmark-generated application Monitoring traces. We show how these scaling rules can be combined and included into semantic SLAs for controlling allocation of services. We also provide a detailed description of the multi-objective infrastructure resource allocation problem and various approaches to satisfying this problem. We present a resource management system based on a genetic algorithm, which performs allocation of virtual resources, while considering the optimization of multiple criteria. We prove that our approach significantly outperforms reactive VM-scaling algorithms as well as heuristic-based VM-allocation approaches.

A Thalamic-Fronto-Parietal Structural Covariance Network Emerging in the Course of Recovery from Hand Paresis after Ischemic Stroke.

AIM To describe structural covariance networks of gray matter volume (GMV) change in 28 patients with first-ever stroke to the primary sensorimotor cortices, and to investigate their relationship to hand function recovery and local GMV change. METHODS Tensor-based morphometry maps derived from high-resolution structural images were subject to principal component analyses to identify the networks. We calculated correlations between network expression and local GMV change, sensorimotor hand function and lesion volume. To verify which of the structural covariance networks of GMV change have a significant relationship to hand function, we performed an additional multivariate regression approach. RESULTS Expression of the second network, explaining 9.1% of variance, correlated with GMV increase in the medio-dorsal (md) thalamus and hand motor skill. Patients with positive expression coefficients were distinguished by significantly higher GMV increase of this structure during stroke recovery. Significant nodes of this network were located in md thalamus, dorsolateral prefrontal cortex, and higher order sensorimotor cortices. Parameter of hand function had a unique relationship to the network and depended on an interaction between network expression and lesion volume. Inversely, network expression is limited in patients with large lesion volumes. CONCLUSION Chronic phase of sensorimotor cortical stroke has been characterized by a large scale co-varying structural network in the ipsilesional hemisphere associated specifically with sensorimotor hand skill. Its expression is related to GMV increase of md thalamus, one constituent of the network, and correlated with the cortico-striato-thalamic loop involved in control of motor execution and higher order sensorimotor cortices. A close relation between expression of this network with degree of recovery might indicate reduced compensatory resources in the impaired subgroup.

Assessment of the role of LASER-Doppler in the treatment of port-wine stains in infants

BACKGROUND Port-wine stains (PWS) are malformations of capillaries in 0.3% of newborn children. The treatment of choice is by pulsed dye LASER (PDL), and requires several sessions. The efficacy of this treatment is at present evaluated on the basis of clinical inspection and of digital photographs taken throughout the treatment. LASER-Doppler imaging (LDI) is a noninvasive method of imaging the perfusion of the tissues by the microcirculatory system (capillaries). The aim of this paper is to demonstrate that LDI allows a quantitative, numerical evaluation of the efficacy of the PDL treatment of PWS. METHOD The PDL sessions were organized according to the usual scheme, every other month, from September 1, 2012, to September 30, 2013. LDI imaging was performed at the start and at the conclusion of the PDL treatment, and simultaneously on healthy skin in order to obtain reference values. The results evidenced by LDI were analyzed according to the "Wilcoxon signed-rank" test before and after each session, and in the intervals between the three PDL treatment sessions. RESULTS Our prospective study is based on 20 new children. On average, the vascularization of the PWS was reduced by 56% after three laser sessions. Compared with healthy skin, initial vascularization of PWS was 62% higher than that of healthy skin at the start of treatment, and 6% higher after three sessions. During the 2 months between two sessions, vascularization of the capillary network increased by 27%. CONCLUSION This study shows that LDI can demonstrate and measure the efficacy of PDL treatment of PWS in children. The figures obtained when measuring the results by LDI corroborate the clinical assessments and may allow us to refine, and perhaps even modify, our present use of PDL and thus improve the efficacy of the treatment.

On the Dark Side of Therapies with Immunoglobulin Concentrates: The Adverse Events

Therapy by human immunoglobulin G (IgG) concentrates is a success story ongoing for decades with an ever increasing demand for this plasma product. The success of IgG concentrates on a clinical level is documented by the slowly increasing number of registered indication and the more rapid increase of the off-label uses, a topic dealt with in another contribution to this special issue of Frontiers in Immunology. A part of the success is the adverse event (AE) profile of IgG concentrates which is, even at life-long need for therapy, excellent. Transmission of pathogens in the last decade could be entirely controlled through the antecedent introduction by authorities of a regulatory network and installing quality standards by the plasma fractionation industry. The cornerstone of the regulatory network is current good manufacturing practice. Non-infectious AEs occur rarely and mainly are mild to moderate. However, in recent times, the increase in frequency of hemolytic and thrombotic AEs raised worrying questions on the possible background for these AEs. Below, we review elements of non-infectious AEs, and particularly focus on hemolysis and thrombosis. We discuss how the introduction of plasma fractionation by ion-exchange chromatography and polishing by immunoaffinity chromatographic steps might alter repertoire of specificities and influence AE profiles and efficacy of IgG concentrates.

Network Dynamics in Natural Resource Governance: A Case Study of Swiss Landscape Management

Structural characteristics of social networks have been recognized as important factors of effective natural resource governance. However, network analyses of natural resource governance most often remain static, even though governance is an inherently dynamic process. In this article, we investigate the evolution of a social network of organizational actors involved in the governance of natural resources in a regional nature park project in Switzerland. We ask how the maturation of a governance network affects bonding social capital and centralization in the network. Applying separable temporal exponential random graph modeling (STERGM), we test two hypotheses based on the risk hypothesis by Berardo and Scholz (2010) in a longitudinal setting. Results show that network dynamics clearly follow the expected trend toward generating bonding social capital but do not imply a shift toward less hierarchical and more decentralized structures over time. We investigate how these structural processes may contribute to network effectiveness over time.

Epileptic networks are strongly connected with and without the effects of interictal discharges

OBJECTIVE Epilepsy is increasingly considered as the dysfunction of a pathologic neuronal network (epileptic network) rather than a single focal source. We aimed to assess the interactions between the regions that comprise the epileptic network and to investigate their dependence on the occurrence of interictal epileptiform discharges (IEDs). METHODS We analyzed resting state simultaneous electroencephalography-functional magnetic resonance imaging (EEG-fMRI) recordings in 10 patients with drug-resistant focal epilepsy with multifocal IED-related blood oxygen level-dependent (BOLD) responses and a maximum t-value in the IED field. We computed functional connectivity (FC) maps of the epileptic network using two types of seed: (1) a 10-mm diameter sphere centered in the global maximum of IED-related BOLD map, and (2) the independent component with highest correlation to the IED-related BOLD map, named epileptic component. For both approaches, we compared FC maps before and after regressing out the effect of IEDs in terms of maximum and mean t-values and percentage of map overlap. RESULTS Maximum and mean FC maps t-values were significantly lower after regressing out IEDs at the group level (p < 0.01). Overlap extent was 85% ± 12% and 87% ± 12% when the seed was the 10-mm diameter sphere and the epileptic component, respectively. SIGNIFICANCE Regions involved in a specific epileptic network show coherent BOLD fluctuations independent of scalp EEG IEDs. FC topography and strength is largely preserved by removing the IED effect. This could represent a signature of a sustained pathologic network with contribution from epileptic activity invisible to the scalp EEG.

Virtual Infrastructures as a Service enabling Converged Optical Networks and Data Centres

Abstract Cloud computing service emerged as an essential component of the Enterprise {IT} infrastructure. Migration towards a full range and large-scale convergence of Cloud and network services has become the current trend for addressing requirements of the Cloud environment. Our approach takes the infrastructure as a service paradigm to build converged virtual infrastructures, which allow offering tailored performance and enable multi-tenancy over a common physical infrastructure. Thanks to virtualization, new exploitation activities of the physical infrastructures may arise for both transport network and Data Centres services. This approach makes network and Data Centres’ resources dedicated to Cloud Computing to converge on the same flexible and scalable level. The work presented here is based on the automation of the virtual infrastructure provisioning service. On top of the virtual infrastructures, a coordinated operation and control of the different resources is performed with the objective of automatically tailoring connectivity services to the Cloud service dynamics. Furthermore, in order to support elasticity of the Cloud services through the optical network, dynamic re-planning features have been provided to the virtual infrastructure service, which allows scaling up or down existing virtual infrastructures to optimize resource utilisation and dynamically adapt to users’ demands. Thus, the dynamic re-planning of the service becomes key component for the coordination of Cloud and optical network resource in an optimal way in terms of resource utilisation. The presented work is complemented with a use case of the virtual infrastructure service being adopted in a distributed Enterprise Information System, that scales up and down as a function of the application requests.