Aspetti etici e morali della Sedazione Palliativa

La sedazione palliativa come procedura terapeutica è ormai ampiamente affrontata e discussa in letteratura. A causa della delicatezza di tale procedura, molti studi affrontano le problematiche etiche ad essa relative con l’obiettivo di cercare una giustificazione morale e clinica. Questo lavoro intende affrontare la sedazione palliativa applicata ad un caso concreto. Seguendo la trama della storia di Matteo, uomo di 38 anni ricoverato in Hospice con diagnosi di cancro metastatico della mammella maschile (metastasi polmonari con incarceramento del polmone destro, metastasi diffuse a tutto il rachide, metastasi epatiche), verranno affrontate le problematiche etiche relative ad ogni fase della vicenda. In particolare i temi trattati sono i seguenti: il controllo di sé, la negoziazione della terapia e l’autodeterminazione; il principio di autonomia relazionale; l’etica del corpo; differenze tra sedazione palliativa ed eutanasia; le domande di fine vita e la spiritualità; documenti sul fine vita. Il paradigma teorico prescelto come punto di riferimento è quello dell’Etica della Cura.

Genetische Mechanismen der dorsoventralen Musterbildung im embryonalen Gehirn von Drosophila

In Vertebraten und Insekten ist während der frühen Entwicklung des zentralen Nervensystems (ZNS), welches sich aus dem Gehirn und dem ventralen Nervensystem (VNS) zusammensetzt, die Unterteilung des Neuroektoderms (NE) in diskrete Genexpressions-Domänen entscheidend für die korrekte Spezifizierung neuraler Stammzellen. In Drosophila wird die Identität dieser Stammzellen (Neuroblasten, NB) festgelegt durch die positionellen Informationen, welche von den Produkten früher Musterbildungsgene bereitgestellt werden und das Neuroektoderm in anteroposteriorer (AP) und dorsoventraler (DV) Achse unterteilen. Die molekulargenetischen Mechanismen, welche der DV-Regionalisierung zugrunde liegen, wurden ausführlich im embryonalen VNS untersucht, sind für das Gehirn jedoch weitestgehend unverstanden. rnIm Rahmen dieser Arbeit wurden neue Erkenntnisse bezüglich der genetischen Mechanismen gewonnen, welche die frühembryonale Anlage des Gehirns in DV-Achse unterteilen. So konnte gezeigt werden, dass das cephale Lückengen empty spiracles (ems), das Segmentpolaritätsgen engrailed (en), sowie der „Epidermal growth factor receptor“ (EGFR) und das Gen Nk6 homeobox (Nkx6) für Faktoren codieren, die als zentrale Regulatoren die DV Musterbildung in der Gehirnanlage kontrollieren. Diese Faktoren interagieren zusammen mit den ebenso evolutionär konservierten Homöobox-Genen ventral nervous system defective (vnd), intermediate neuroblasts defective (ind) und muscle segment homeobox (msh) in einem komplexen, regulatorischen DV-Netzwerk. Die im Trito (TC)- und Deutocerebrum (DC) entschlüsselten genetischen Interaktionen basieren überwiegend auf wechselseitiger Repression. Dementsprechend sorgen 1) Vnd und Ems durch gegenseitige Repression für eine frühe DV-Unterteilung des NE, und 2) wechselseitige Repression zwischen Nkx6 und Msh, als auch zwischen Ind und Msh für die Aufrechterhaltung der Grenze zwischen intermediärem und dorsalem NE. 3) Sowohl Ind als auch Msh sind in der Lage, die Expression von vnd zu inhibieren. Ferner konnte gezeigt werden, dass Vnd durch Repression von Msh als positiver Regulator von Nkx6 fungiert. Überdies beeinflusst Vnd die Expression von ind in segment-spezifischer Art und Weise: Vnd reprimiert ind-Expression im TC, sorgt jedoch für eine positive Regulation von ind im DC durch Repression von Msh. Auch der EGFR-Signalweg ist an der frühen DV-Regionalisierung des Gehirns beteiligt, indem er durch positive Regulation der msh-Repressoren Vnd, Ind und Nkx6 dazu beiträgt, dass die Expression von msh auf dorsales NE beschränkt bleibt. Ferner stellte sich heraus, dass das AP-Musterbildungsgen ems die Expression der DV-Gene kontrolliert und umgekehrt: Ems ist für die Aktivierung von Nkx6, ind und msh in TC und DC erforderlich ist, während Nkx6 und Ind zu einem späteren Zeitpunkt benötigt werden, um ems im intermediären DC gemeinsam zu reprimieren. Überdies konnte gezeigt werden, dass das Segmentpolaritätsgen en Aspekte der Expression von vnd, ind und msh in segment-spezifischer Art und Weise reguliert. En reprimiert ind und msh, hält jedoch vnd-Expression im DC aufrecht; im TC wird En benötigt, um die Expression von Msh herunter zu regulieren und somit die Aktivierung von ind dort zu ermöglichen.rnrnZusammengenommen zeigen diese Ergebnisse, dass AP Musterbildungsfaktoren in umfangreichen Maß die Expression der DV Gene im Gehirn (und VNS) kontrollieren. Ferner deuten diese Daten darauf hin, dass sich das „Konzept der ventralen Dominanz“, welches für die DV-Musterbildung im VNS postuliert wurde, nicht auf das genregulatorische Netzwerk im Gehirn übertragen lässt, da Interaktionen zwischen den beteiligten Faktoren hauptsächlich auf wechselseitiger (und nicht einseitiger) Repression basieren. Zudem scheint das Konzept der ventralen Dominanz auch für das VNS nicht uneingeschränkt zu gelten, da in dieser Arbeit u.a. gezeigt werden konnte, dass dorsal exprimiertes Msh in der Lage ist, intermediäres ind zu reprimieren. Interessanterweise ist gegenseitige Repression von Homöodomänen-Proteinen im sich entwickelnden Neuralrohr von Vertebraten weit verbreitet und darüberhinaus essenziell für den Aufbau diskreter DV-Vorläuferdomänen, und weist insofern eine große Ähnlichkeit zu den in dieser Arbeit beschriebenen DV-Musterbildungsvorgängen im frühembryonalen Fliegengehirn auf.rn

La cooperazione amministrativa tra stati membri in materia fiscale: verso una amministrazione finanziaria "europea"

L’armonizzazione fiscale è una importante sfida che l’Unione Europea si trova ad affrontare per la completa realizzazione del mercato interno. Le istituzioni comunitarie, tuttavia, non dispongono delle competenze legislative per intervenire direttamente negli ordinamenti tributari degli Stati membri. Svolgendo una analisi del contesto legislativo vigente, ed esaminando le prospettive de iure condendo della materia fiscale dell’Unione, il presente lavoro cerca di comprendere le prospettive di evoluzione del sistema, sia dal punto di vista della normativa fiscale sostanziale, che procedimentale. Mediante la disciplina elaborata a livello comunitario che regola la cooperazione amministrativa in materia fiscale, con particolare riferimento alle direttive relative allo scambio di informazioni e all’assistenza alla riscossione (dir. 2011/16/UE e dir. 2010/24/UE) si permette alle Amministrazioni degli Stati membri di avere accesso ai reciproci ordinamenti giuridici, e conoscerne i meccanismi. L’attuazione di tali norme fa sì che ciascun ordinamento abbia l’opportunità di importare le best practices implementate dagli altri Stati. L’obiettivo sarà quello di migliorare il proprio procedimento amministrativo tributario, da un lato, e di rendere più immediati gli scambi di informazione e la cooperazione alla riscossione, dall’altro. L’armonizzazione fiscale all’interno dell’Unione verrebbe perseguita, anziché mediante un intervento a livello europeo, attraverso un coordinamento “dal basso” degli ordinamenti fiscali, realizzato attraverso l’attività di cooperazione delle amministrazioni che opereranno su un substrato di regole condivise. La maggiore apertura delle amministrazioni fiscali dei Paesi membri e la maggiore spontaneità degli scambi di informazioni, ha una efficacia deterrente di fenomeni di evasione e di sottrazione di imposta posti in essere al fine di avvantaggiarsi delle differenze dei sistemi impositivi dei vari paesi. Nel lungo periodo ciò porterà verosimilmente, gli Stati membri a livellare i sistemi impositivi, dal momento che i medesimi non avranno più interesse ad utilizzare la leva fiscale per generare una concorrenza tra gli ordinamenti.

A Law and Economics Analysis of Lobbying Regulation Towards an optimal structure through the Cost Indicator Index

This research primarily represents a contribution to the lobbying regulation research arena. It introduces an index which for the first time attempts to measure the direct compliance costs of lobbying regulation. The Cost Indicator Index (CII) offers a brand new platform for qualitative and quantitative assessment of adopted lobbying laws and proposals of those laws, both in the comparative and the sui generis dimension. The CII is not just the only new tool introduced in the last decade, but it is the only tool available for comparative assessments of the costs of lobbying regulations. Beside the qualitative contribution, the research introduces an additional theoretical framework for complementary qualitative analysis of the lobbying laws. The Ninefold theory allows a more structured assessment and classification of lobbying regulations, both by indication of benefits and costs. Lastly, this research introduces the Cost-Benefit Labels (CBL). These labels might improve an ex-ante lobbying regulation impact assessment procedure, primarily in the sui generis perspective. In its final part, the research focuses on four South East European countries (Slovenia, Serbia, Montenegro and Macedonia), and for the first time brings them into the discussion and calculates their CPI and CII scores. The special focus of the application was on Serbia, whose proposal on the Law on Lobbying has been extensively analysed in qualitative and quantitative terms, taking into consideration specific political and economic circumstances of the country. Although the obtained results are of an indicative nature, the CII will probably find its place within the academic and policymaking arena, and will hopefully contribute to a better understanding of lobbying regulations worldwide.

The Application of European Competition Law in Arbitration Proceedings

This work provides several policy proposals capable to strengthen the private enforcement of EU competition law in arbitration. It focuses on the procedural law aspects that are permeated by legal uncertainty and that have not yet fallen under the scrutiny of the law and economics debate. The policy proposals described herein are based on the functional approach to law and economics and aim to promote a more qualified decision making process by: adjudicators, private parties and lawmakers. The resulting framework of procedural rules would be a cost-effective policy tool that could sustain the European Commission’s effort to guarantee a workable level of competition in the EU internal market. This project aims to answer the following broad research question: which procedural rules can improve the efficiency of antitrust arbitration by decreasing litigation costs for private parties on the one hand, and by increasing private parties’ compliance with competition law on the other hand?Throughout this research project, such broad question has been developed into research sub-questions revolving around several key legal issues. The chosen sub-research questions result from a vacuum in the European enforcement system that leaves several key legal issues in antitrust arbitration unresolved. The legal framework proposed in this research project could prevent such a blurry scenario from impairing the EU private enforcement of competition law in arbitration. Therefore, our attention was triggered by those legal issues whose proposed solutions lead to relevant uncertainties and that are most suitable for a law and economics analysis.

Social Welfare and Behavioral Public Policies

In this work I discuss several key aspects of welfare economics and policy analysis and I propose two original contributions to the growing field of behavioral public policymaking. After providing a historical perspective of welfare economics and an overview of policy analysis processes in the introductory chapter, in chapter 2 I discuss a debated issue of policymaking, the choice of the social welfare function. I contribute to this debate by proposing an original methodological contribution based on the analysis of the quantitative relationship among different social welfare functional forms commonly used by policy analysts. In chapter 3 I then discuss a behavioral policy to contrast indirect tax evasion based on the use of lotteries. I show that the predictions of my model based on non-expected utility are consistent with observed, and so far unexplained, empirical evidence of the policy success. Finally, in chapter 4 I investigate by mean of a laboratory experiment the effects of social influence on the individual likelihood to engage in altruistic punishment. I show that bystanders’ decision to engage in punishment is influenced by the punishment behavior of their peers and I suggest ways to enact behavioral policies that exploit this finding.

The market manipulation regime in the European Union

Market manipulation is an illegal practice that enables a person can profit from practices that artificially raise or lower the prices of an instrument in the financial markets. Its prohibition is based on the 2003 Market Abuse Directive in the EU. The current market manipulation regime was broadly considered as a big success except for enforcement and supervisory inconsistencies in the Member States at the initial. A review of the market manipulation regime began at the end of 2007, which became quickly incorporated into the wider EU crisis-era reform program. A number of weaknesses of current regime have been identified, which include regulatory gaps caused by the development of trading venues and financial products, regulatory gaps concerning cross-border and cross-markets manipulation (particular commodity markets), legal uncertainty as a result of various implementation, and inefficient supervision and enforcement. On 12 June 2014, a new regulatory package of market abuse, Market Abuse Regulation and Directive on criminal sanctions for market abuse, has been adopted. And several changes will be made concerning the EU market manipulation regime. A wider scope of the regime and a new prohibition of attempted market manipulation will ensure the prevention of market manipulation at large. The AMPs will be subject to strict scrutiny of ESMA to reduce divergences in implementation. In order to enhance efficiency of supervision and enforcement, powers of national competent authorities will be strengthened, ESMA is imposed more power to settle disagreement between national regulators, and the administrative and criminal sanctioning regimes are both further harmonized. In addition, the protection of fundamental rights is stressed by the new market manipulation regime, and some measures are provided to guarantee its realization. Further, the success EU market manipulation regime could be of significant reference to China, helping China to refine its immature regime.

Nucleon electromagnetic structure studies in the spacelike and timelike regions

The thesis investigates the nucleon structure probed by the electromagnetic interaction. One of the most basic observables, reflecting the electromagnetic structure of the nucleon, are the form factors, which have been studied by means of elastic electron-proton scattering with ever increasing precision for several decades. In the timelike region, corresponding with the proton-antiproton annihilation into a electron-positron pair, the present experimental information is much less accurate. However, in the near future high-precision form factor measurements are planned. About 50 years after the first pioneering measurements of the electromagnetic form factors, polarization experiments stirred up the field since the results were found to be in striking contradiction to the findings of previous form factor investigations from unpolarized measurements. Triggered by the conflicting results, a whole new field studying the influence of two-photon exchange corrections to elastic electron-proton scattering emerged, which appeared as the most likely explanation of the discrepancy. The main part of this thesis deals with theoretical studies of two-photon exchange, which is investigated particularly with regard to form factor measurements in the spacelike as well as in the timelike region. An extraction of the two-photon amplitudes in the spacelike region through a combined analysis using the results of unpolarized cross section measurements and polarization experiments is presented. Furthermore, predictions of the two-photon exchange effects on the e+p/e-p cross section ratio are given for several new experiments, which are currently ongoing. The two-photon exchange corrections are also investigated in the timelike region in the process pbar{p} -> e+ e- by means of two factorization approaches. These corrections are found to be smaller than those obtained for the spacelike scattering process. The influence of the two-photon exchange corrections on cross section measurements as well as asymmetries, which allow a direct access of the two-photon exchange contribution, is discussed. Furthermore, one of the factorization approaches is applied for investigating the two-boson exchange effects in parity-violating electron-proton scattering. In the last part of the underlying work, the process pbar{p} -> pi0 e+e- is analyzed with the aim of determining the form factors in the so-called unphysical, timelike region below the two-nucleon production threshold. For this purpose, a phenomenological model is used, which provides a good description of the available data of the real photoproduction process pbar{p} -> pi0 gamma.

Doveri e responsabilita' degli amministratori nella crisi dei gruppi di societa'

Il presente studio si propone di individuare i doveri e le responsabilità, di tipo risarcitorio, degli amministratori, in particolare degli amministratori della società che esercita attività di direzione e coordinamento, in una situazione di crisi o insolvenza nel gruppo, anche in un’ottica di “prevenzione”, e, più precisamente, il complesso di regole di corretta gestione societaria e imprenditoriale, con le quali il silenzio della legge fallimentare in tema di gruppi di società non può non confrontarsi. In particolare, si indagherà sulla possibilità di individuare nel nostro ordinamento giuridico, nel momento di emersione della crisi, doveri di comportamento in capo agli organi di governo della società o ente che esercita attività di direzione e coordinamento, al fine di fronteggiare la crisi, evitando il peggioramento della stessa, ovvero per un risanamento anticipato e, quindi, più suscettibile di esito positivo, nella prospettiva di tutela dei soci c.d. esterni e dei creditori delle società figlie e, nello stesso tempo, dei soci della capogruppo medesima e, quindi, in una prospettiva più ampia e articolata rispetto a una società individualmente considerata. L’oggetto dell’analisi viene introdotto mediante un inquadramento generale della disciplina in materia di gruppi di società presente nel nostro sistema normativo, con particolare riguardo alla disciplina dell’attività di direzione e coordinamento introdotta dal legislatore della riforma del diritto societario (d.lgs. 17 gennaio 2003, n. 6) con gli artt. 2497 ss. cod. civ.. Nella seconda parte verranno individuati e approfonditi i criteri e i principi dai quali ricavare le regole di governance nei gruppi di società e la relativa responsabilità degli amministratori nelle situazioni di crisi nel gruppo. Sulla scorta delle suddette argomentazioni, nell'ultima parte verranno individuate le regole di gestione nell'ambito del gruppo nel momento di “emersione” della crisi e, in particolare, i possibili “strumenti” che il nostro legislatore offre per fronteggiarla.

La fiscalità delle perdite dei gruppi transfrontalieri: tra regimi nazionali e libertà di stabilimento

Caratteristica comune ai regimi di consolidamento previsti dai diversi ordinamenti, è quella di consentire la compensazione tra utili e perdite di società residenti, e, di negare, o rendere particolarmente difficoltosa, la stessa compensazione, quando le perdite sono maturate da società non residenti. La non considerazione delle perdite comporta una tassazione al lordo del gruppo multinazionale, per mezzo della quale, non si colpisce il reddito effettivo dei soggetti che vi appartengono. L’effetto immediato è quello di disincentivare i gruppi a travalicare i confini nazionali. Ciò impedisce il funzionamento del Mercato unico, a scapito della libertà di stabilimento prevista dagli artt. 49-54 del TFUE. Le previsioni ivi contenute sono infatti dirette, oltre ad assicurare a società straniere il beneficio della disciplina dello Stato membro ospitante, a proibire altresì allo Stato di origine di ostacolare lo stabilimento in un altro Stato membro dei propri cittadini o delle società costituite conformemente alla propria legislazione. Gli Stati membri giustificano la discriminazione tra società residenti e non residenti alla luce della riserva di competenza tributaria ad essi riconosciuta dall’ordinamento europeo in materia delle imposte dirette, dunque, in base all’equilibrata ripartizione del potere impositivo. In assenza di qualsiasi riferimento normativo, va ascritto alla Corte di Giustizia il ruolo di interprete del diritto europeo. La Suprema Corte, con una serie di importanti pronunce, ha infatti sindacato la compatibilità con il diritto comunitario dei vari regimi interni che negano la compensazione transfrontaliera delle perdite. Nel verificare la compatibilità con il diritto comunitario di tali discipline, la Corte ha tentato di raggiungere un (difficile) equilibrio tra due interessi completamenti contrapposti: quello comunitario, riconducibile al rispetto della libertà di stabilimento, quello degli Stati membri, che rivendicano il diritto di esercitare il proprio potere impositivo.

Einfluss Zelltod-inhibierender Proteine des murinen Cytomegalovirus auf die Initiation der antiviralen CD8 T-Zellantwort

Die Inhibition des programmierten Zelltods ist ein essentieller Faktor der viralen Replikationsfähigkeit. Das murine Cytomegalovirus kodiert deshalb für verschiedene Zelltod-inhibierende Gene, um dem programmierten Zelltod zu entgehen bis die Virusproduktion abgeschlossen ist. Da die Expression des viralen anti-apoptotischen Gens M36 infizierte Makrophagen vor der Apoptose schützt (Menard et al., 2003), wurde in der vorliegenden Arbeit unter Verwendung der Deletionsmutante mCMV-ΔM36 (ΔM36) der Einfluss von Apoptose auf das Priming Epitop-spezifischer CD8 T-Zellen untersucht.rnInteressanterweise waren die Frequenzen mCMV-spezifischer CD8 T-Zellen nach Infektion mit ΔM36 für alle getesteten Epitope sowohl im Haplotyp H-2d als auch im Haplotyp H-2b deutlich erhöht. Zusätzlich konnte mit Hilfe der mCMV-ORF-Library eine Verbreiterung des CD8 T-Zellepitop-Repertoire nach Infektion mit ΔM36 nachgewiesen werden, was neben der quantitativen auch eine qualitative Steigerung des CD8 T-Zell-Primings aufzeigt.rnIn der funktionellen Revertante ΔM36-FADDDN wird die anti-apoptotische Funktion durch eine dominant-negative Form des zellulären Adapterproteins FADD (FADDDN) substituiert (Cicin-Sain et al., 2008), die das Apoptose-Signaling verhindert. In der vorliegenden Arbeit konnte gezeigt werden, dass die Expression von FADDDN nicht nur den Apoptose-Phänotyp wieder revertiert, sondern auch die Verbesserung des CD8 T-Zell-Primings aufhebt. Diese Beobachtung belegt eindeutig, dass das verbesserte CD8 T-Zell-Priming auf einer verstärkten Apoptose-Induktion beruht.Bemerkenswerterweise konnte das verbesserte Priming auch nach Deletion des anti-nekroptotischen Gens M45 nachgewiesen werden. So konnte nach Infektion mit mCMV-M45-BamX (M45-BamX) (Brune et al., 2001) gezeigt werden, dass auch die Induktion der Nekroptose zu einem verbesserten CD8 T-Zell-Priming sowie zu einer Verbreiterung des CD8 T-Zellepitop-Repertoires führt.Nach Infektion von Cross-Priming-defizienten 3d-Mäusen (Tabeta et al., 2006) konnte eine Steigerung mCMV-spezifischer CD8 T-Zell-Frequenzen in Abwesenheit von M36 oder M45 nicht beobachtet werden. Dieser Befund lässt auf ein erhöhtes Cross-Priming von CD8 T-Zellen durch ΔM36 oder M45-BamX infolge einer verstärkten Induktion des programmierten Zelltods schließen.rnIn der vorliegenden Arbeit konnte erstmals gezeigt werden, dass die Inhibition des programmierten Zelltods durch die mCMV-Gene M36 und M45 das CD8 T-Zell-Priming limitiert. Somit fördern virale Zelltod-inhibierende Gene die virale Replikationsfähigkeit, indem sie die Virusproduktion per se in der individuellen Zelle steigern und zusätzlich die Immunkontrolle reduzieren, was wiederum eine verbesserte Dissemination in vivo ermöglicht.

Visualization and validation of (Q)SAR models

Analyzing and modeling relationships between the structure of chemical compounds, their physico-chemical properties, and biological or toxic effects in chemical datasets is a challenging task for scientific researchers in the field of cheminformatics. Therefore, (Q)SAR model validation is essential to ensure future model predictivity on unseen compounds. Proper validation is also one of the requirements of regulatory authorities in order to approve its use in real-world scenarios as an alternative testing method. However, at the same time, the question of how to validate a (Q)SAR model is still under discussion. In this work, we empirically compare a k-fold cross-validation with external test set validation. The introduced workflow allows to apply the built and validated models to large amounts of unseen data, and to compare the performance of the different validation approaches. Our experimental results indicate that cross-validation produces (Q)SAR models with higher predictivity than external test set validation and reduces the variance of the results. Statistical validation is important to evaluate the performance of (Q)SAR models, but does not support the user in better understanding the properties of the model or the underlying correlations. We present the 3D molecular viewer CheS-Mapper (Chemical Space Mapper) that arranges compounds in 3D space, such that their spatial proximity reflects their similarity. The user can indirectly determine similarity, by selecting which features to employ in the process. The tool can use and calculate different kinds of features, like structural fragments as well as quantitative chemical descriptors. Comprehensive functionalities including clustering, alignment of compounds according to their 3D structure, and feature highlighting aid the chemist to better understand patterns and regularities and relate the observations to established scientific knowledge. Even though visualization tools for analyzing (Q)SAR information in small molecule datasets exist, integrated visualization methods that allows for the investigation of model validation results are still lacking. We propose visual validation, as an approach for the graphical inspection of (Q)SAR model validation results. New functionalities in CheS-Mapper 2.0 facilitate the analysis of (Q)SAR information and allow the visual validation of (Q)SAR models. The tool enables the comparison of model predictions to the actual activity in feature space. Our approach reveals if the endpoint is modeled too specific or too generic and highlights common properties of misclassified compounds. Moreover, the researcher can use CheS-Mapper to inspect how the (Q)SAR model predicts activity cliffs. The CheS-Mapper software is freely available at http://ches-mapper.org.

A prediction model for assessing residential radon concentration in Switzerland

Indoor radon is regularly measured in Switzerland. However, a nationwide model to predict residential radon levels has not been developed. The aim of this study was to develop a prediction model to assess indoor radon concentrations in Switzerland. The model was based on 44,631 measurements from the nationwide Swiss radon database collected between 1994 and 2004. Of these, 80% randomly selected measurements were used for model development and the remaining 20% for an independent model validation. A multivariable log-linear regression model was fitted and relevant predictors selected according to evidence from the literature, the adjusted R², the Akaike's information criterion (AIC), and the Bayesian information criterion (BIC). The prediction model was evaluated by calculating Spearman rank correlation between measured and predicted values. Additionally, the predicted values were categorised into three categories (50th, 50th-90th and 90th percentile) and compared with measured categories using a weighted Kappa statistic. The most relevant predictors for indoor radon levels were tectonic units and year of construction of the building, followed by soil texture, degree of urbanisation, floor of the building where the measurement was taken and housing type (P-values <0.001 for all). Mean predicted radon values (geometric mean) were 66 Bq/m³ (interquartile range 40-111 Bq/m³) in the lowest exposure category, 126 Bq/m³ (69-215 Bq/m³) in the medium category, and 219 Bq/m³ (108-427 Bq/m³) in the highest category. Spearman correlation between predictions and measurements was 0.45 (95%-CI: 0.44; 0.46) for the development dataset and 0.44 (95%-CI: 0.42; 0.46) for the validation dataset. Kappa coefficients were 0.31 for the development and 0.30 for the validation dataset, respectively. The model explained 20% overall variability (adjusted R²). In conclusion, this residential radon prediction model, based on a large number of measurements, was demonstrated to be robust through validation with an independent dataset. The model is appropriate for predicting radon level exposure of the Swiss population in epidemiological research. Nevertheless, some exposure misclassification and regression to the mean is unavoidable and should be taken into account in future applications of the model.

Echinococcus multilocularis and its intermediate host: a model of parasite-host interplay

Host-parasite interactions in the E. multilocularis-intermediate host model depend on a subtle balance between cellular immunity, which is responsible for host's resistance towards the metacestode, the larval stage of the parasite, and tolerance induction and maintenance. The pathological features of alveolar echinococcosis. the disease caused by E. multilocularis, are related both to parasitic growth and to host's immune response, leading to fibrosis and necrosis, The disease spectrum is clearly dependent on the genetic background of the host as well as on acquired disturbances of Th1-related immunity. The laminated layer of the metacestode, and especially its carbohydrate components, plays a major role in tolerance induction. Th2-type and anti-inflammatory cytokines, IL-10 and TGF-beta, as well as nitric oxide, are involved in the maintenance of tolerance and partial inhibition of cytotoxic mechanisms. Results of studies in the experimental mouse model and in patients suggest that immune modulation with cytokines, such as interferon-alpha, or with specific antigens could be used in the future to treat patients with alveolar echinococcosis and/or to prevent this very severe parasitic disease.

An Investigation On The Use Of Microalgae For Biogas Enrichment

There is a need for biomethane capture and carbon dioxide sequestration to mitigate evident global climate change. This research work investigated the potential for microalgae to remove CO2 from biogas as a biotechnical method for upgrading the thermal value for subsequent compression, liquification, or introduction to natural gas pipelines. Because biogas is largely methane, the effect of high methane environments on mixed microalgae was explored and found that specific carbon utilization rates were not statistically different when microalgae were exposed to biogas environments (70% v/v CH4) , relative to high CO2 environment. The uses of conventional bubbled column photobioreactors (PBR) were assessed for CO2 removal and subsequent CH4 enrichment. A continuously-bubbled biogas PBR (cB-PBR5) and intermittently-bubbled biogas PBR (iB-PBR) experienced CO2 loading rates of about 1664 and 832 mg C/L*day and showed 30.0 and 60.1 % carbon removal, respectively. However, a lack of biogas enrichment and issues associated growth inhibition due to high CO2 environments as well as stripping the dissolved gases, namely oxygen and nitrogen, from the bulk liquid and introduction to the outlet gas prompted the consideration for gas/liquid separation using nonporous hollow-fiber (HF) membranes for CO2 transfer. The potential for two non-porous HF membrane materials [polydimethylsiloxane (PDMS) and composite polyurethane (PU)] were modeled along fiber length using a mechanistic model based on polymeric material transport properties (Gilmore et al., 2009). Based on a high CO2:CH4 permeability selectivity for PU of 76.2 the model predicted gas enrichment along an 8.5 cm fiber length. Because PDMS permeability selectivity is low (3.5), evident gas transfer was not predicated along a 34.3 cm length. Both of these HF materials were implemented in hollow-fiber membrane-carbonated biofilm (HFMcB) PBRs for microalgal-mediated biogas enrichment. Phototrophic biofilm colonization occurred on the membrane, where CO2 concentration was greatest. The presence of a biofilm demonstrated greater resiliency to high CO2 environments, compared to the conventional PBRs. However, as the PDMS model predicted, the PDMS HFMcBs did not demonstrate gas enrichment. These reactors received CO2 loading rates of 200 mg C/L*day based on PDMS permeability flux and showed approximately 65% removal of the total C transferred across the membrane. Thus, the HFMcBs demonstrated controlled carbonation of the bulk liquid via a nonporous HF membrane. Likewise, the experimental PU HFMcB did not show gas enrichment yet this result should be further explored due to the high permeability selectivity of the polymeric material. Chemical stratifications, namely pH and dissolved O2, present in a PDMS membrane-carbonated biofilm were analyzed using electrochemical microsensors. Results indicated that high DO (20 mg L-1) exists at surface of the biofilm where light availability is greatest and low pH microenvironments (pH=5.40) exist deep in the biofilm where the diffusive flux of CO2 drives transfer through the biofilm. The presence of a 400-600 ¿m liquid phase boundary layer was evident from microsensor profiles. Cryosectioning of the biofilm samples showed the biofilm to be approximately 1.17 ± 0.07 mm thick, suggesting that the high localized concentration of biomass associated with the phototrophic biofilm aided in overcoming inhibition in a microenvironment dominated by CO2(aq). Challenges of biofilm detachment and PBR fouling as well as microalgal growth inhibition in the presence of high CO2 content remain for applications of microalgae for biogas enrichment.