The sympathetic nervous system regulates the three glycerol-3P generation pathways in white adipose tissue of fasted, diabetic and high-protein diet-fed rats

The aim of the present study was to investigate the participation of the sympathetic nervous system (SNS) in the control of glycerol-3-P (G3P) generating pathways in white adipose tissue (WAT) of rats in three situations in which the plasma insulin levels are low. WAT from 48 h fasted animals, 3 day-streptozotocin diabetic animals and high-protein, carbohydrate-free (HP) diet-fed rats was surgical denervated and the G3P generation pathways were evaluated. Food deprivation, diabetes and the HP diet provoke a marked decrease in the rate of glucose uptake and glycerokinase (GyK) activity, but a significant increase in the glyceroneogenesis, estimated by the phosphoenolpyruvate carboxykinase (PEPCK) activity and the incorporation of 1-[C-14]-pyruvate into glycerol-TAG. The denervation provokes a reduction (similar to 70%) in the NE content of WAT in fasted, diabetic and HP diet-fed rats. The denervation induced an increase in WAT glucose uptake of fed, fasted, diabetic and HP diet-fed rats (40%, 60%, 3.2 fold and 35%, respectively). TAG-glycerol synthesis from pyruvate was reduced by denervation in adipocytes of fed (58%) and fasted (36%), saline-treated (58%) and diabetic (23%), and HP diet-fed rats (11%). In these same groups the denervation reduced the PEPCK mRNA expression (75%-95%) and the PEPCK activity (35%-60%). The denervation caused a similar to 35% decrease in GyK activity of control rats and a further similar to 35% reduction in the already low enzyme activity of fasted, diabetic and HP diet-fed rats. These data suggest that the SNS plays an important role in modulating G3P generating pathways in WAT, in situations where insulin levels are low. (C) 2012 Elsevier Inc. All rights reserved.

A Fuzzy Ontology-Driven Approach to Semantic Interoperability in e-Government Big Data

With the increasing production of information from e-government initiatives, there is also the need to transform a large volume of unstructured data into useful information for society. All this information should be easily accessible and made available in a meaningful and effective way in order to achieve semantic interoperability in electronic government services, which is a challenge to be pursued by governments round the world. Our aim is to discuss the context of e-Government Big Data and to present a framework to promote semantic interoperability through automatic generation of ontologies from unstructured information found in the Internet. We propose the use of fuzzy mechanisms to deal with natural language terms and present some related works found in this area. The results achieved in this study are based on the architectural definition and major components and requirements in order to compose the proposed framework. With this, it is possible to take advantage of the large volume of information generated from e-Government initiatives and use it to benefit society.

Probabilistic approaches in civil engineering: generation of random fields and structural identification with genetic algorithms

The inherent stochastic character of most of the physical quantities involved in engineering models has led to an always increasing interest for probabilistic analysis. Many approaches to stochastic analysis have been proposed. However, it is widely acknowledged that the only universal method available to solve accurately any kind of stochastic mechanics problem is Monte Carlo Simulation. One of the key parts in the implementation of this technique is the accurate and efficient generation of samples of the random processes and fields involved in the problem at hand. In the present thesis an original method for the simulation of homogeneous, multi-dimensional, multi-variate, non-Gaussian random fields is proposed. The algorithm has proved to be very accurate in matching both the target spectrum and the marginal probability. The computational efficiency and robustness are very good too, even when dealing with strongly non-Gaussian distributions. What is more, the resulting samples posses all the relevant, welldefined and desired properties of “translation fields”, including crossing rates and distributions of extremes. The topic of the second part of the thesis lies in the field of non-destructive parametric structural identification. Its objective is to evaluate the mechanical characteristics of constituent bars in existing truss structures, using static loads and strain measurements. In the cases of missing data and of damages that interest only a small portion of the bar, Genetic Algorithm have proved to be an effective tool to solve the problem.

The rupture process of recent tsunamigenic earthquakes by geophysical data inversion

Subduction zones are the favorite places to generate tsunamigenic earthquakes, where friction between oceanic and continental plates causes the occurrence of a strong seismicity. The topics and the methodologies discussed in this thesis are focussed to the understanding of the rupture process of the seismic sources of great earthquakes that generate tsunamis. The tsunamigenesis is controlled by several kinematical characteristic of the parent earthquake, as the focal mechanism, the depth of the rupture, the slip distribution along the fault area and by the mechanical properties of the source zone. Each of these factors plays a fundamental role in the tsunami generation. Therefore, inferring the source parameters of tsunamigenic earthquakes is crucial to understand the generation of the consequent tsunami and so to mitigate the risk along the coasts. The typical way to proceed when we want to gather information regarding the source process is to have recourse to the inversion of geophysical data that are available. Tsunami data, moreover, are useful to constrain the portion of the fault area that extends offshore, generally close to the trench that, on the contrary, other kinds of data are not able to constrain. In this thesis I have discussed the rupture process of some recent tsunamigenic events, as inferred by means of an inverse method. I have presented the 2003 Tokachi-Oki (Japan) earthquake (Mw 8.1). In this study the slip distribution on the fault has been inferred by inverting tsunami waveform, GPS, and bottom-pressure data. The joint inversion of tsunami and geodetic data has revealed a much better constrain for the slip distribution on the fault rather than the separate inversions of single datasets. Then we have studied the earthquake occurred on 2007 in southern Sumatra (Mw 8.4). By inverting several tsunami waveforms, both in the near and in the far field, we have determined the slip distribution and the mean rupture velocity along the causative fault. Since the largest patch of slip was concentrated on the deepest part of the fault, this is the likely reason for the small tsunami waves that followed the earthquake, pointing out how much the depth of the rupture plays a crucial role in controlling the tsunamigenesis. Finally, we have presented a new rupture model for the great 2004 Sumatra earthquake (Mw 9.2). We have performed the joint inversion of tsunami waveform, GPS and satellite altimetry data, to infer the slip distribution, the slip direction, and the rupture velocity on the fault. Furthermore, in this work we have presented a novel method to estimate, in a self-consistent way, the average rigidity of the source zone. The estimation of the source zone rigidity is important since it may play a significant role in the tsunami generation and, particularly for slow earthquakes, a low rigidity value is sometimes necessary to explain how a relatively low seismic moment earthquake may generate significant tsunamis; this latter point may be relevant for explaining the mechanics of the tsunami earthquakes, one of the open issues in present day seismology. The investigation of these tsunamigenic earthquakes has underlined the importance to use a joint inversion of different geophysical data to determine the rupture characteristics. The results shown here have important implications for the implementation of new tsunami warning systems – particularly in the near-field – the improvement of the current ones, and furthermore for the planning of the inundation maps for tsunami-hazard assessment along the coastal area.

Advanced signal and receiver design for next generation OFDM systems

This thesis deal with the design of advanced OFDM systems. Both waveform and receiver design have been treated. The main scope of the Thesis is to study, create, and propose, ideas and novel design solutions able to cope with the weaknesses and crucial aspects of modern OFDM systems. Starting from the the transmitter side, the problem represented by low resilience to non-linear distortion has been assessed. A novel technique that considerably reduces the Peak-to-Average Power Ratio (PAPR) yielding a quasi constant signal envelope in the time domain (PAPR close to 1 dB) has been proposed.The proposed technique, named Rotation Invariant Subcarrier Mapping (RISM),is a novel scheme for subcarriers data mapping,where the symbols belonging to the modulation alphabet are not anchored, but maintain some degrees of freedom. In other words, a bit tuple is not mapped on a single point, rather it is mapped onto a geometrical locus, which is totally or partially rotation invariant. The final positions of the transmitted complex symbols are chosen by an iterative optimization process in order to minimize the PAPR of the resulting OFDM symbol. Numerical results confirm that RISM makes OFDM usable even in severe non-linear channels. Another well known problem which has been tackled is the vulnerability to synchronization errors. Indeed in OFDM system an accurate recovery of carrier frequency and symbol timing is crucial for the proper demodulation of the received packets. In general, timing and frequency synchronization is performed in two separate phases called PRE-FFT and POST-FFT synchronization. Regarding the PRE-FFT phase, a novel joint symbol timing and carrier frequency synchronization algorithm has been presented. The proposed algorithm is characterized by a very low hardware complexity, and, at the same time, it guarantees very good performance in in both AWGN and multipath channels. Regarding the POST-FFT phase, a novel approach for both pilot structure and receiver design has been presented. In particular, a novel pilot pattern has been introduced in order to minimize the occurrence of overlaps between two pattern shifted replicas. This allows to replace conventional pilots with nulls in the frequency domain, introducing the so called Silent Pilots. As a result, the optimal receiver turns out to be very robust against severe Rayleigh fading multipath and characterized by low complexity. Performance of this approach has been analytically and numerically evaluated. Comparing the proposed approach with state of the art alternatives, in both AWGN and multipath fading channels, considerable performance improvements have been obtained. The crucial problem of channel estimation has been thoroughly investigated, with particular emphasis on the decimation of the Channel Impulse Response (CIR) through the selection of the Most Significant Samples (MSSs). In this contest our contribution is twofold, from the theoretical side, we derived lower bounds on the estimation mean-square error (MSE) performance for any MSS selection strategy,from the receiver design we proposed novel MSS selection strategies which have been shown to approach these MSE lower bounds, and outperformed the state-of-the-art alternatives. Finally, the possibility of using of Single Carrier Frequency Division Multiple Access (SC-FDMA) in the Broadband Satellite Return Channel has been assessed. Notably, SC-FDMA is able to improve the physical layer spectral efficiency with respect to single carrier systems, which have been used so far in the Return Channel Satellite (RCS) standards. However, it requires a strict synchronization and it is also sensitive to phase noise of local radio frequency oscillators. For this reason, an effective pilot tone arrangement within the SC-FDMA frame, and a novel Joint Multi-User (JMU) estimation method for the SC-FDMA, has been proposed. As shown by numerical results, the proposed scheme manages to satisfy strict synchronization requirements and to guarantee a proper demodulation of the received signal.

Generation and characterization of mouse models of Small cell lung cancer and Basal cell carcinoma for the preclinical evaluation of new therapies

Background. Human small cell lung cancer (SCLC) accounting for approximately 15-20% of all lung cancers, is an aggressive tumor with high propensity for early regional and distant metastases. Although the initial tumor rate response to chemotherapy is very high, SCLC relapses after approximately 4 months in ED and 12 months in LD. Basal cell carcinoma (BCC) is the most prevalent cancer in the western world, and its incidence is increasing worldwide. This type of cancer rarely metastasizes and the death rate is extraordinary low. Surgery is curative for most of the patients, but for those that develop locally advanced or metastatic BCC there is currently no effective treatment. Both types of cancer have been deeply investigated and genetic alterations, MYCN amplification (MA) among the most interesting, have been found. These could become targets of new pharmacological therapies. Procedures. We created and characterized novel BLI xenograft orthotopic mouse models of SCLC to evaluate the tumor onset and progression and the efficacy of new pharmacological strategies. We compared an in vitro model with a transgenic mouse model of BCC, to investigate and delineate the canonical HH signalling pathway and its connections with other molecular pathways. Results and conclusions. The orthotopic models showed latency and progression patterns similar to human disease. Chemotherapy treatments improved survival rates and validated the in vivo model. The presence of MA and overexpression were confirmed in each model and we tested the efficacy of a new MYCN inhibitor in vitro. Preliminar data of BCC models highlighted Hedgehog pathway role and underlined the importance of both in vitro and in vivo strategies to achieve a better understanding of the pathology and to evaluate the applicability of new therapeutic compounds

Development of new tools and devices for CMB and foreground data analysis and future experiments

The discovery of the Cosmic Microwave Background (CMB) radiation in 1965 is one of the fundamental milestones supporting the Big Bang theory. The CMB is one of the most important source of information in cosmology. The excellent accuracy of the recent CMB data of WMAP and Planck satellites confirmed the validity of the standard cosmological model and set a new challenge for the data analysis processes and their interpretation. In this thesis we deal with several aspects and useful tools of the data analysis. We focus on their optimization in order to have a complete exploitation of the Planck data and contribute to the final published results. The issues investigated are: the change of coordinates of CMB maps using the HEALPix package, the problem of the aliasing effect in the generation of low resolution maps, the comparison of the Angular Power Spectrum (APS) extraction performances of the optimal QML method, implemented in the code called BolPol, and the pseudo-Cl method, implemented in Cromaster. The QML method has been then applied to the Planck data at large angular scales to extract the CMB APS. The same method has been applied also to analyze the TT parity and the Low Variance anomalies in the Planck maps, showing a consistent deviation from the standard cosmological model, the possible origins for this results have been discussed. The Cromaster code instead has been applied to the 408 MHz and 1.42 GHz surveys focusing on the analysis of the APS of selected regions of the synchrotron emission. The new generation of CMB experiments will be dedicated to polarization measurements, for which are necessary high accuracy devices for separating the polarizations. Here a new technology, called Photonic Crystals, is exploited to develop a new polarization splitter device and its performances are compared to the devices used nowadays.

Differential expression analysis for sequence count data via mixtures of negative binomials

The recent advent of Next-generation sequencing technologies has revolutionized the way of analyzing the genome. This innovation allows to get deeper information at a lower cost and in less time, and provides data that are discrete measurements. One of the most important applications with these data is the differential analysis, that is investigating if one gene exhibit a different expression level in correspondence of two (or more) biological conditions (such as disease states, treatments received and so on). As for the statistical analysis, the final aim will be statistical testing and for modeling these data the Negative Binomial distribution is considered the most adequate one especially because it allows for "over dispersion". However, the estimation of the dispersion parameter is a very delicate issue because few information are usually available for estimating it. Many strategies have been proposed, but they often result in procedures based on plug-in estimates, and in this thesis we show that this discrepancy between the estimation and the testing framework can lead to uncontrolled first-type errors. We propose a mixture model that allows each gene to share information with other genes that exhibit similar variability. Afterwards, three consistent statistical tests are developed for differential expression analysis. We show that the proposed method improves the sensitivity of detecting differentially expressed genes with respect to the common procedures, since it is the best one in reaching the nominal value for the first-type error, while keeping elevate power. The method is finally illustrated on prostate cancer RNA-seq data.

Identification of novel genetic alterations in pediatric cytogenetically normal acute myeloid leukemia by next-generation sequencing

Pediatric acute myeloid leukemia (AML) is a molecularly heterogeneous disease that arises from genetic alterations in pathways that regulate self-renewal and myeloid differentiation. While the majority of patients carry recurrent chromosomal translocations, almost 20% of childhood AML do not show any recognizable cytogenetic alteration and are defined as cytogenetically normal (CN)-AML. CN-AML patients have always showed a great variability in response to therapy and overall outcome, underlining the presence of unknown genetic changes, not detectable by conventional analyses, but relevant for pathogenesis, and outcome of AML. The development of novel genome-wide techniques such as next-generation sequencing, have tremendously improved our ability to interrogate the cancer genome. Based on this background, the aim of this research study was to investigate the mutational landscape of pediatric CN-AML patients negative for all the currently known somatic mutations reported in AML through whole-transcriptome sequencing (RNA-seq). RNA-seq performed on diagnostic leukemic blasts from 19 pediatric CN-AML cases revealed a considerable incidence of cryptic chromosomal rearrangements, with the identification of 21 putative fusion genes. Several of the fusion genes that were identified in this study are recurrent and might have a prognostic and/or therapeutic relevance. A paradigm of that is the CBFA2T3-GLIS2 fusion, which has been demonstrated to be a common alteration in pediatric CN-AML, predicting poor outcome. Important findings have been also obtained in the identification of novel therapeutic targets. On one side, the identification of NUP98-JARID1A fusion suggests the use of disulfiram; on the other, here we describe alteration-activating tyrosine kinases, providing functional data supporting the use of tyrosine kinase inhibitors to specifically inhibit leukemia cells. This study provides new insights in the knowledge of genetic alterations underlying pediatric AML, defines novel prognostic markers and putative therapeutic targets, and prospectively ensures a correct risk stratification and risk-adapted therapy also for the “all-neg” AML subgroup.

Charge generation and recombination in hybrid organic,inorganic solar cells

This thesis deals with the investigation of exciton and charge dynamics in hybrid solar cells by time-resolved optical spectroscopy. Quasi-steady-state and transient absorption spectroscopy, as well as time-resolved photoluminescence spectroscopy, were employed to study charge generation and recombination in solid-state organic dye-sensitized solar cells, where the commonly used liquid electrolyte is replaced by an organic solid hole transporter, namely 2,2′7,7′-tetrakis-(N,N-di-p-methoxyphenyl-amine)-9,9′-spirobifluorene (spiro-MeOTAD), and polymer-metal oxide bulk heterojunction solar cells, where the commonly used fullerene acceptor [6,6]-phenyl C61 butyric acid methyl ester (PCBM) is replaced by zinc oxide (ZnO) nanoparticles. By correlating the spectroscopic results with the photovoltaic performance, efficiency-limiting processes and processes leading to photocurrent generation in the investigated systems are revealed. rnIt is shown that the charge generation from several all-organic donor-π-bridge-acceptor dyes, specifically perylene monoimide derivatives, employed in solid-state dye-sensitized solar cells, is strongly dependent on the presence of a commonly used additive lithium bis(trifluoromethanesulphonyl)imide salt (Li-TFSI) at the interface. rnMoreover, it is shown that charges can not only be generated by electron injection from the excited dye into the TiO2 acceptor and subsequent regeneration of the dye cation by the hole transporter, but also by an alternative mechanism, called preceding hole transfer (or reductive quenching). Here, the excited dye is first reduced by the hole transporter and the thereby formed anion subsequently injects an electron into the titania. This additional charge generation process, which is only possible for solid hole transporters, helps to overcome injection problems. rnHowever, a severe disadvantage of solid-state dye-sensitized solar cells is re-vealed by monitoring the transient Stark effect on dye molecules at the inter-face induced by the electric field between electrons and holes. The attraction between the negative image charge present in TiO2, which is induced by the positive charge carrier in the hole transporter due to the dielectric contrast between the organic spiro-MeOTAD and inorganic titania, is sufficient to at-tract the hole back to the interface, thereby increasing recombination and suppressing the extraction of free charges.rnBy investigating the effect of different dye structures and physical properties on charge generation and recombination, design rules and guidelines for the further advancement of solid-state dye-sensitized solar cells are proposed.rnFinally, a spectroscopic study on polymer:ZnO bulk heterojunction hybrid solar cells, employing different surfactants attached to the metal oxide nanoparticles, was performed to understand the effect of surfactants upon photovoltaic behavior. By applying a parallel pool analysis on the transient absorption data, it is shown that suppressing fast recombination while simultaneously maintaining the exciton splitting efficiency by the right choice of surfactants leads to better photovoltaic performances. Suppressing the fast recombination completely, whilst maintaining the exciton splitting, could lead to a doubling of the power conversion efficiency of this type of solar cell.

Optimized scheduling in real-time environments with column generation

Im Bereich sicherheitsrelevanter eingebetteter Systeme stellt sich der Designprozess von Anwendungen als sehr komplex dar. Entsprechend einer gegebenen Hardwarearchitektur lassen sich Steuergeräte aufrüsten, um alle bestehenden Prozesse und Signale pünktlich auszuführen. Die zeitlichen Anforderungen sind strikt und müssen in jeder periodischen Wiederkehr der Prozesse erfüllt sein, da die Sicherstellung der parallelen Ausführung von größter Bedeutung ist. Existierende Ansätze können schnell Designalternativen berechnen, aber sie gewährleisten nicht, dass die Kosten für die nötigen Hardwareänderungen minimal sind. Wir stellen einen Ansatz vor, der kostenminimale Lösungen für das Problem berechnet, die alle zeitlichen Bedingungen erfüllen. Unser Algorithmus verwendet Lineare Programmierung mit Spaltengenerierung, eingebettet in eine Baumstruktur, um untere und obere Schranken während des Optimierungsprozesses bereitzustellen. Die komplexen Randbedingungen zur Gewährleistung der periodischen Ausführung verlagern sich durch eine Zerlegung des Hauptproblems in unabhängige Unterprobleme, die als ganzzahlige lineare Programme formuliert sind. Sowohl die Analysen zur Prozessausführung als auch die Methoden zur Signalübertragung werden untersucht und linearisierte Darstellungen angegeben. Des Weiteren präsentieren wir eine neue Formulierung für die Ausführung mit fixierten Prioritäten, die zusätzlich Prozessantwortzeiten im schlimmsten anzunehmenden Fall berechnet, welche für Szenarien nötig sind, in denen zeitliche Bedingungen an Teilmengen von Prozessen und Signalen gegeben sind. Wir weisen die Anwendbarkeit unserer Methoden durch die Analyse von Instanzen nach, welche Prozessstrukturen aus realen Anwendungen enthalten. Unsere Ergebnisse zeigen, dass untere Schranken schnell berechnet werden können, um die Optimalität von heuristischen Lösungen zu beweisen. Wenn wir optimale Lösungen mit Antwortzeiten liefern, stellt sich unsere neue Formulierung in der Laufzeitanalyse vorteilhaft gegenüber anderen Ansätzen dar. Die besten Resultate werden mit einem hybriden Ansatz erzielt, der heuristische Startlösungen, eine Vorverarbeitung und eine heuristische mit einer kurzen nachfolgenden exakten Berechnungsphase verbindet.

Charge generation and recombination in solid-state dye-sensitized solar cells

Diese Doktorarbeit befasst sich mit Ladungsgeneration und – rekombination in Feststoff-Farbstoffsolarzellen, die spiro-OMeTAD als Lochleiter verwenden. Die vorliegende Arbeit ist in drei Fallstudien unterteilt: i.) Kern-erweiterte Rylen-Farbstoffe, ii.) ein Perylenmonoimid-Farbstoff und iii.) Donor-π verbrückte (Cyclopentadithiophen)-Akzeptor-Farbstoffe. Trotz ihres hohen molaren Extinktionskoeffizienten und der hohen Absorbanz der sensibilisierten Filme, zeigen einige dieser Farbstoffmoleküle nur geringe photovoltaischen Effizienzen. Um den Ursprung des geringen Wirkungsgrades herauszufinden, wurde breitbandige, ultraschnelle transiente Absorptionsspektroskopie an Solarzellen durchgeführt.rnInsbesondere die Auswirkungen verschiedender Ankergruppen, Dipolmomente, Photolumineszenzlebenszeiten, Lithium-Kationensensitivität und Ladungsträgerdynamik, die alle einen großen Einfluss auf den Wirkungsgrad der Solarzelle besitzen, wurden untersucht. In der ersten Fallstudie zeigte ein kurzer Rylen-Farbstoff aufgrund deutlich verlängerter Lebenszeiten die beste Effizienz im Vergleich zu größeren Kern-erweiterten Rylen-Farbstoffen. Die Lebenszeit wurde weiter reduziert, wenn Maleinsäure als Ankergruppe unter einer Ringöffnungsreaktion an die mesoporöse Oberfläche des Metalloxid-Halbleiters adsorbierte. Dies konnte mit Hilfe von Berechnungen mittels der Dichtefunktionaltheorie (DFT, B3LYP) auf die Differenz des Dipolmoments zwischen Grundzustand und angeregtem Zustand zurückgeführt werden. Die Berechnungen bekräftigen die unvorteilhafte Injektion von Ladungen durch die Änderung der Richtung des Dipolmoments, wenn eine Ringöffnung der Anhydridgruppe stattfindet. In der zweiten Studie zeigte das Perylenmonoimid-Derivat ID889 einen Wirkungsgrad von 4.5% in Feststoff-Farbstoffsolarzellen, wobei ID889 sogar ohne Zuhilfenahme eines Additivs in der Lage ist langlebige Farbstoffkationen zu bilden. Die Verwendung von Lithium-Kationen stabilisiert jedoch sowohl den Prozess der Ladungsgeneration als auch den der Ladungsregeneration. Des Weiteren wurde in ID889-sensitivierten Bauteilen kein reduktives Löschen beobachtet. Dabei wurde die Dynamik der Exzitonen mittels einer soft-modelling Methode Kurvenanalyse aus den Daten der transienten Absorptionsspektroskopie gewonnen. Zuletzt wurden Strukturen mit Cyclopentadithiophen(CPDT)-Baustein untersucht, die eine typische D-π-A Molekülstruktur bilden. FPH224 und 233 zeigten dabei eine bessere Effizienz als FPH231 und 303 aufgrund einer großen Injektionseffizienz (IE) und längerer Lebenszeit der angeregten Zustände. Dies kann auf reduktives Löschen in FPH231 und 303 zurückgeführt werden, wohingegen FPH224 und 233 einen moderaten Zerfall des Spirokationensignals zeigten.

Toward optimal display of physiologic status in critical care: I. Recreating bedside displays from archived physiologic data

BACKGROUND: Physiologic data display is essential to decision making in critical care. Current displays echo first-generation hemodynamic monitors dating to the 1970s and have not kept pace with new insights into physiology or the needs of clinicians who must make progressively more complex decisions about their patients. The effectiveness of any redesign must be tested before deployment. Tools that compare current displays with novel presentations of processed physiologic data are required. Regenerating conventional physiologic displays from archived physiologic data is an essential first step. OBJECTIVES: The purposes of the study were to (1) describe the SSSI (single sensor single indicator) paradigm that is currently used for physiologic signal displays, (2) identify and discuss possible extensions and enhancements of the SSSI paradigm, and (3) develop a general approach and a software prototype to construct such "extended SSSI displays" from raw data. RESULTS: We present Multi Wave Animator (MWA) framework-a set of open source MATLAB (MathWorks, Inc., Natick, MA, USA) scripts aimed to create dynamic visualizations (eg, video files in AVI format) of patient vital signs recorded from bedside (intensive care unit or operating room) monitors. Multi Wave Animator creates animations in which vital signs are displayed to mimic their appearance on current bedside monitors. The source code of MWA is freely available online together with a detailed tutorial and sample data sets.

Benchmarking in the SWISSspine registry: results of 52 Dynardi lumbar total disc replacements compared with the data pool of 431 other lumbar disc prostheses

The SWISSspine registry is the first mandatory registry of its kind in the history of Swiss orthopaedics and it follows the principle of "coverage with evidence development". Its goal is the generation of evidence for a decision by the Swiss federal office of health about reimbursement of the concerned technologies and treatments by the basic health insurance of Switzerland. Recently, developed and clinically implemented, the Dynardi total disc arthroplasty (TDA) accounted for 10% of the implanted lumbar TDAs in the registry. We compared the outcomes of patients treated with Dynardi to those of the recipients of the other TDAs in the registry. Between March 2005 and October 2009, 483 patients with single-level TDA were documented in the registry. The 52 patients with a single Dynardi lumbar disc prosthesis implanted by two surgeons (CE and OS) were compared to the 431 patients who received one of the other prostheses. Data were collected in a prospective, observational multicenter mode. Surgery, implant, 3-month, 1-year, and 2-year follow-up forms as well as comorbidity, NASS and EQ-5D questionnaires were collected. For statistical analyses, the Wilcoxon signed-rank test and chi-square test were used. Multivariate regression analyses were also performed. Significant and clinically relevant reduction of low back pain and leg pain as well as improvement in quality of life was seen in both groups (P < 0.001 postop vs. preop). There were no inter-group differences regarding postoperative pain levels, intraoperative and follow-up complications or revision procedures with a new hospitalization. However, significantly more Dynardi patients achieved a minimum clinically relevant low back pain alleviation of 18 VAS points and a quality of life improvement of 0.25 EQ-5D points. The patients with Dynardi prosthesis showed a similar outcome to patients receiving the other TDAs in terms of postoperative low back and leg pain, complications, and revision procedures. A higher likelihood for achieving a minimum clinically relevant improvement of low back pain and quality of life in Dynardi patients was observed. This difference might be due to the large number of surgeons using other TDAs compared to only two surgeons using the Dynardi TDA, with corresponding variations in patient selection, patient-physician interaction and other factors, which cannot be assessed in a registry study.

Generation and characterization of stable, highly concentrated titanium dioxide nanoparticle aerosols for rodent inhalation studies

The intensive use of nano-sized titanium dioxide (TiO2) particles in many different applications necessitates studies on their risk assessment as there are still open questions on their safe handling and utilization. For reliable risk assessment, the interaction of TiO2 nanoparticles (NP) with biological systems ideally needs to be investigated using physico-chemically uniform and well-characterized NP. In this article, we describe the reproducible production of TiO2 NP aerosols using spark ignition technology. Because currently no data are available on inhaled NP in the 10–50 nm diameter range, the emphasis was to generate NP as small as 20 nm for inhalation studies in rodents. For anticipated in vivo dosimetry analyses, TiO2 NP were radiolabeled with 48V by proton irradiation of the titanium electrodes of the spark generator. The dissolution rate of the 48V label was about 1% within the first day. The highly concentrated, polydisperse TiO2 NP aerosol (3–6 × 106 cm−3) proved to be constant over several hours in terms of its count median mobility diameter, its geometric standard deviation, and number concentration. Extensive characterization of NP chemical composition, physical structure, morphology, and specific surface area was performed. The originally generated amorphous TiO2 NP were converted into crystalline anatase TiO2 NP by thermal annealing at 950 °C. Both crystalline and amorphous 20-nm TiO2 NP were chain agglomerated/aggregated, consisting of primary particles in the range of 5 nm. Disintegration of the deposited TiO2 NP in lung tissue was not detectable within 24 h.