La concezione epistemica dell'analiticità: un dibattito in corso

Il lavoro è una riflessione sugli sviluppi della nozione di definizione nel recente dibattito sull'analiticità. La rinascita di questa discussione, dopo le critiche di Quine e un conseguente primo abbandono della concezione convenzionalista carnapiana ha come conseguenza una nuova concezione epistemica dell'analiticità. Nella maggior parte dei casi le nuove teorie epistemiche, tra le quali quelle di Bob Hale e Crispin Wright (Implicit Definition and the A priori, 2001) e Paul Boghossian (Analyticity, 1997; Epistemic analyticity, a defence, 2002, Blind reasoning, 2003, Is Meaning Normative ?, 2005) presentano il comune carattere di intendere la conoscenza a priori nella forma di una definizione implicita (Paul Horwich, Stipulation, Meaning, and Apriority, 2001). Ma una seconda linea di obiezioni facenti capo dapprima a Horwich, e in seguito agli stessi Hale e Wright, mettono in evidenza rispettivamente due difficoltà per la definizione corrispondenti alle questioni dell'arroganza epistemica e dell'accettazione (o della stipulazione) di una definizione implicita. Da questo presupposto nascono diversi tentativi di risposta. Da un lato, una concezione della definizione, nella teoria di Hale e Wright, secondo la quale essa appare come un principio di astrazione, dall'altro una nozione della definizione come definizione implicita, che si richiama alla concezione di P. Boghossian. In quest'ultima, la definizione implicita è data nella forma di un condizionale linguistico (EA, 2002; BR, 2003), ottenuto mediante una fattorizzazione della teoria costruita sul modello carnapiano per i termini teorici delle teorie empiriche. Un'analisi attenta del lavoro di Rudolf Carnap (Philosophical foundations of Physics, 1966), mostra che la strategia di scomposizione rappresenta una strada possibile per una nozione di analiticità adeguata ai termini teorici. La strategia carnapiana si colloca, infatti, nell'ambito di un tentativo di elaborazione di una nozione di analiticità che tiene conto degli aspetti induttivi delle teorie empiriche

The challenges and the limitations in Life Cycle Impact Assessment for metal oxide nanoparticles, a case study on nano- TiO2

Life Cycle Assessment (LCA) is a chain-oriented tool to evaluate the environment performance of products focussing on the entire life cycle of these products: from the extraction of resources, via manufacturing and use, to the final processing of the disposed products. Through all these stages consumption of resources and pollutant releases to air, water, soil are identified and quantified in Life Cycle Inventory (LCI) analysis. Subsequently to the LCI phase follows the Life Cycle Impact Assessment (LCIA) phase; that has the purpose to convert resource consumptions and pollutant releases in environmental impacts. The LCIA aims to model and to evaluate environmental issues, called impact categories. Several reports emphasises the importance of LCA in the field of ENMs. The ENMs offer enormous potential for the development of new products and application. There are however unanswered questions about the impacts of ENMs on human health and the environment. In the last decade the increasing production, use and consumption of nanoproducts, with a consequent release into the environment, has accentuated the obligation to ensure that potential risks are adequately understood to protect both human health and environment. Due to its holistic and comprehensive assessment, LCA is an essential tool evaluate, understand and manage the environmental and health effects of nanotechnology. The evaluation of health and environmental impacts of nanotechnologies, throughout the whole of their life-cycle by using LCA methodology. This is due to the lack of knowledge in relation to risk assessment. In fact, to date, the knowledge on human and environmental exposure to nanomaterials, such ENPs is limited. This bottleneck is reflected into LCA where characterisation models and consequently characterisation factors for ENPs are missed. The PhD project aims to assess limitations and challenges of the freshwater aquatic ecotoxicity potential evaluation in LCIA phase for ENPs and in particular nanoparticles as n-TiO2.

Functional and Genetic characterization of new genomic islands from an E. coli strain associated with neonatal meningitis.

Enterobacteriaceae genomes evolve through mutations, rearrangements and horizontal gene transfer (HGT). The latter evolutionary pathway works through the acquisition DNA (GEI) modules of foreign origin that enhances fitness of the host to a given environment. The genome of E. coli IHE3034, a strain isolated from a case of neonatal meningitis, has recently been sequenced and its subsequent sequence analysis has predicted 18 possible GEIs, of which: 8 have not been previously described, 5 fully meet the pathogenic island definition and at least 10 that seem to be of prophagic origin. In order to study the GEI distribution of our reference strain, we screened for the presence 18 GEIs a panel of 132 strains, representative of E. coli diversity. Also, using an inverse nested PCR approach we identified 9 GEI that can form an extrachromosomal circular intermediate (CI) and their respective attachment sites (att). Further, we set up a qPCR approach that allowed us to determine the excision rates of 5 genomic islands in different growth conditions. Four islands, specific for strains appertaining to the sequence type complex 95 (STC95), have been deleted in order to assess their function in a Dictyostelium discoideum grazing assays. Overall, the distribution data presented here indicate that 16 IHE3034 GEIs are more associated to the STC95 strains. Also the functional and genetic characterization has uncovered that GEI 13, 17 and 19 are involved in the resistance to phagocitation by Dictyostelium d thus suggesting a possible role in the adaptation of the pathogen during certain stages of infection.

An Input-Process-Output Approach to Interorganizational Teams: The Influence of Work Group Diversity, Trust and Shared Leadership on Communication Network and Team Outputs.

The market’s challenges bring firms to collaborate with other organizations in order to create Joint Ventures, Alliances and Consortia that are defined as “Interorganizational Networks” (IONs) (Provan, Fish and Sydow; 2007). Some of these IONs are managed through a shared partecipant governance (Provan and Kenis, 2008): a team composed by entrepreneurs and/or directors of each firm of an ION. The research is focused on these kind of management teams and it is based on an input-process-output model: some input variables (work group’s diversity, intra-team's friendship network density) have a direct influence on the process (team identification, shared leadership, interorganizational trust, team trust and intra-team's communication network density), which influence some team outputs, individual innovation behaviors and team effectiveness (team performance, work group satisfaction and ION affective commitment). Data was collected on a sample of 101 entrepreneurs grouped in 28 ION’s government teams and the research hypotheses are tested trough the path analysis and the multilevel models. As expected trust in team and shared leadership are positively and directly related to team effectiveness while team identification and interorganizational trust are indirectly related to the team outputs. The friendship network density among the team’s members has got positive effects on the trust in team and on the communication network density, and also, through the communication network density it improves the level of the teammates ION affective commitment. The shared leadership and its effects on the team effectiveness are fostered from higher level of team identification and weakened from higher level of work group diversity, specifically gender diversity. Finally, the communication network density and shared leadership at the individual level are related to the frequency of individual innovative behaviors. The dissertation’s results give a wider and more precise indication about the management of interfirm network through “shared” form of governance.

Copper and zinc stable isotope ratios as tracers of biogeochemical processes, sources and transport of Cu and Zn in soils

Copper and Zn are essential micronutrients for plants, animals, and humans; however, they may also be pollutants if they occur at high concentrations in soil. Therefore, knowledge of Cu and Zn cycling in soils is required both for guaranteeing proper nutrition and to control possible risks arising from pollution.rnThe overall objective of my study was to test if Cu and Zn stable isotope ratios can be used to investigate into the biogeochemistry, source and transport of these metals in soils. The use of stable isotope ratios might be especially suitable to trace long-term processes occurring during soil genesis and transport of pollutants through the soil. In detail, I aimed to answer the questions, whether (1) Cu stable isotopes are fractionated during complexation with humic acid, (2) 65Cu values can be a tracer for soil genetic processes in redoximorphic soils (3) 65Cu values can help to understand soil genetic processes under oxic weathering conditions, and (4) 65Cu and 66Zn values can act as tracers of sources and transport of Cu and Zn in polluted soils.rnTo answer these questions, I ran adsorption experiments at different pH values in the laboratory and modelled Cu adsorption to humic acid. Furthermore, eight soils were sampled representing different redox and weathering regimes of which two were influenced by stagnic water, two by groundwater, two by oxic weathering (Cambisols), and two by podzolation. In all horizons of these soils, I determined selected basic soil properties, partitioned Cu into seven operationally defined fractions and determined Cu concentrations and Cu isotope ratios (65Cu values). Finally, three additional soils were sampled along a deposition gradient at different distances to a Cu smelter in Slovakia and analyzed together with bedrock and waste material from the smelter for selected basic soil properties, Cu and Zn concentrations and 65Cu and 66Zn values.rnMy results demonstrated that (1) Copper was fractionated during adsorption on humic acid resulting in an isotope fractionation between the immobilized humic acid and the solution (65CuIHA-solution) of 0.26 ± 0.11‰ (2SD) and that the extent of fractionation was independent of pH and involved functional groups of the humic acid. (2) Soil genesis and plant cycling causes measurable Cu isotope fractionation in hydromorphic soils. The results suggested that an increasing number of redox cycles depleted 63Cu with increasing depth resulting in heavier 65Cu values. (3) Organic horizons usually had isotopically lighter Cu than mineral soils presumably because of the preferred uptake and recycling of 63Cu by plants. (4) In a strongly developed Podzol, eluviation zones had lighter and illuviation zones heavier 65Cu values because of the higher stability of organo-65Cu complexes compared to organo-63Cu complexes. In the Cambisols and a little developed Podzol, oxic weathering caused increasingly lighter 65Cu values with increasing depth, resulting in the opposite depth trend as in redoximorphic soils, because of the preferential vertical transport of 63Cu. (5) The 66Zn values were fractionated during the smelting process and isotopically light Zn was emitted allowing source identification of Zn pollution while 65Cu values were unaffected by the smelting and Cu emissions isotopically indistinguishable from soil. The 65Cu values in polluted soils became lighter down to a depth of 0.4 m indicating isotope fractionation during transport and a transport depth of 0.4 m in 60 years. 66Zn values had an opposite depth trend becoming heavier with depth because of fractionation by plant cycling, speciation changes, and mixing of native and smelter-derived Zn. rnCopper showed measurable isotope fractionation of approximately 1‰ in unpolluted soils, allowing to draw conclusions on plant cycling, transport, and redox processes occurring during soil genesis and 65Cu and 66Zn values in contaminated soils allow for conclusions on sources (in my study only possible for Zn), biogeochemical behavior, and depth of dislocation of Cu and Zn pollution in soil. I conclude that stable Cu and Zn isotope ratios are a suitable novel tool to trace long-term processes in soils which are difficult to assess otherwise.rn

Peak-to-Peak Output Current Ripple Analysis in Multiphase and Multilevel Inverters

Analysis of the peak-to-peak output current ripple amplitude for multiphase and multilevel inverters is presented in this PhD thesis. The current ripple is calculated on the basis of the alternating voltage component, and peak-to-peak value is defined by the current slopes and application times of the voltage levels in a switching period. Detailed analytical expressions of peak-to-peak current ripple distribution over a fundamental period are given as function of the modulation index. For all the cases, reference is made to centered and symmetrical switching patterns, generated either by carrier-based or space vector PWM. Starting from the definition and the analysis of the output current ripple in three-phase two-level inverters, the theoretical developments have been extended to the case of multiphase inverters, with emphasis on the five- and seven-phase inverters. The instantaneous current ripple is introduced for a generic balanced multiphase loads consisting of series RL impedance and ac back emf (RLE). Simplified and effective expressions to account for the maximum of the output current ripple have been defined. The peak-to-peak current ripple diagrams are presented and discussed. The analysis of the output current ripple has been extended also to multilevel inverters, specifically three-phase three-level inverters. Also in this case, the current ripple analysis is carried out for a balanced three-phase system consisting of series RL impedance and ac back emf (RLE), representing both motor loads and grid-connected applications. The peak-to-peak current ripple diagrams are presented and discussed. In addition, simulation and experimental results are carried out to prove the validity of the analytical developments in all the cases. The cases with different phase numbers and with different number of levels are compared among them, and some useful conclusions have been pointed out. Furthermore, some application examples are given.

Knots and links in lens spaces

The aim of this dissertation is to improve the knowledge of knots and links in lens spaces. If the lens space L(p,q) is defined as a 3-ball with suitable boundary identifications, then a link in L(p,q) can be represented by a disk diagram, i.e. a regular projection of the link on a disk. In this contest, we obtain a complete finite set of Reidemeister-type moves establishing equivalence, up to ambient isotopy. Moreover, the connections of this new diagram with both grid and band diagrams for links in lens spaces are shown. A Wirtinger-type presentation for the group of the link and a diagrammatic method giving the first homology group are described. A class of twisted Alexander polynomials for links in lens spaces is computed, showing its correlation with Reidemeister torsion. One of the most important geometric invariants of links in lens spaces is the lift in 3-sphere of a link L in L(p,q), that is the counterimage of L under the universal covering of L(p,q). Starting from the disk diagram of the link, we obtain a diagram of the lift in the 3-sphere. Using this construction it is possible to find different knots and links in L(p,q) having equivalent lifts, hence we cannot distinguish different links in lens spaces only from their lift. The two final chapters investigate whether several existing invariants for links in lens spaces are essential, i.e. whether they may assume different values on links with equivalent lift. Namely, we consider the fundamental quandle, the group of the link, the twisted Alexander polynomials, the Kauffman Bracket Skein Module and an HOMFLY-PT-type invariant.

Governo, strutture e trasformazioni nel sistema universitario

L’elaborato costituisce la fase di approfondimento conclusivo del lavoro scientifico svolto negli anni precedenti. In quest’ottica, a circa tre anni dalla sua entrata in vigore, esso risulta prevalentemente incentrato sull’analisi delle principali innovazioni imposte dalla legge 30 dicembre 2010, n . 240, recante "Norme in materia di organizzazione delle università, di personale accademico e reclutamento, nonché delega al Governo per incentivare la qualità e l'efficienza del sistema universitario", nel tentativo di individuare quali soluzioni ,più o meno differenziate in base alle specificità delle diverse realtà, gli atenei italiani abbiano prefigurato mediante la revisione dei propri statuti, organi e strutture, al fine di rispettare ed attuare il dettato legislativo e non comprimere i propri spazi di autonomia. Contemporaneamente, esso approfondisce l’orientamento della giurisprudenza amministrativa in materia, la quale proprio nel corso di quest’anno ha avuto più di un’occasione di pronunciarsi in merito, per effetto dell’impugnazione ministeriale di molti dei nuovi statuti di autonomia. Infine, non viene tralasciata l’analisi dei profili e aspetti del sistema universitario italiano non intaccati dal cambiamento, ai fini del loro coordinamento con quelli riformati, cercando di percorrere parallelamente più strade: dalla ricognizione e lo studio dei più autorevoli contributi che la dottrina ha recentemente elaborato in materia, all’inquadramento delle scelte effettuate in sede di attuazione dai singoli atenei, anche alla luce dei decreti applicativi emanati. Il tutto al fine di individuare, anche grazie a studi di tipo comparato, con particolare riferimento all’ordinamento spagnolo, nuove soluzioni per il sistema universitario che, senza la pretesa di giungere a percorsi di cambiamento validamente applicabili per tutti gli atenei, possano risultare utili alla definizione di principi e modelli base, nel pieno rispetto del dettato costituzionale e dei parametri individuati a livello europeo con il processo di Bologna e la strategia di Lisbona.

Qualita' istituzionale e capitale sociale: Un'analisi regionale

Il capitale sociale e la qualità istituzionale sono due fenomeni che, da circa venti anni, hanno assunto il ruolo di protagonisti all’interno delle scienze sociali. Anche se per molto tempo sono stati analizzati separatamente, già dalla loro definizione è possibile intuire come essi rappresentino due facce della stessa medaglia. Questo lavoro ha l’obiettivo di comprendere quale è le relazione che lega il capitale sociale e la qualità istituzionale all’interno delle regioni dell’Unione Europea. Nonostante buona parte della letteratura si sia maggiormente dedicata all’analisi dei due fenomeni a livello nazionale, in questo elaborato si ritiene che la dimensione territoriale regionale sia l’unità di misura più idonea per analizzarli entrambi. La prima parte del lavoro analizza il capitale sociale sia da un punto di vista definitorio che da un punto di vista più prettamente empirico, suddividendolo in diversi elementi. Il capitale sociale è un fenomeno estremamente multidimensionale, analizzarne solo una parte condurrebbe ad un’analisi parziale ed approssimativa. All’interno del testo vengono individuate cinque dimensioni, utilizzate successivamente per la creazione di un nuovo indice di capitale sociale regionale. Nella seconda parte si affronta il tema delle istituzioni e della qualità istituzionale. Dopo aver definito le istituzioni, si provvede ad effettuare una rassegna degli indici più comunemente utilizzati per misurarne la qualità, selezionando l’European Quality of Government Index del Quality of Government Institute di Göteborg come il più appropriato, sia per la sua definizione di governance che per l’unità di analisi prescelta. Nella terza parte, infine, in seguito ad un’analisi di quella parte di letteratura che ritiene i due fenomeni indissolubilmente legati ed utilizzando l’indice di capitale sociale regionale sviluppato nel primo capitolo, si propone una risposta, sicuramente parziale e non definitiva, alla domanda che da vent’anni anima questo interessante filone di ricerca: che relazione sussiste tra qualità istituzionale e capitale sociale?

Modelling and simulating in systems biology: an approach based on multi-agent systems

Systems Biology is an innovative way of doing biology recently raised in bio-informatics contexts, characterised by the study of biological systems as complex systems with a strong focus on the system level and on the interaction dimension. In other words, the objective is to understand biological systems as a whole, putting on the foreground not only the study of the individual parts as standalone parts, but also of their interaction and of the global properties that emerge at the system level by means of the interaction among the parts. This thesis focuses on the adoption of multi-agent systems (MAS) as a suitable paradigm for Systems Biology, for developing models and simulation of complex biological systems. Multi-agent system have been recently introduced in informatics context as a suitabe paradigm for modelling and engineering complex systems. Roughly speaking, a MAS can be conceived as a set of autonomous and interacting entities, called agents, situated in some kind of nvironment, where they fruitfully interact and coordinate so as to obtain a coherent global system behaviour. The claim of this work is that the general properties of MAS make them an effective approach for modelling and building simulations of complex biological systems, following the methodological principles identified by Systems Biology. In particular, the thesis focuses on cell populations as biological systems. In order to support the claim, the thesis introduces and describes (i) a MAS-based model conceived for modelling the dynamics of systems of cells interacting inside cell environment called niches. (ii) a computational tool, developed for implementing the models and executing the simulations. The tool is meant to work as a kind of virtual laboratory, on top of which kinds of virtual experiments can be performed, characterised by the definition and execution of specific models implemented as MASs, so as to support the validation, falsification and improvement of the models through the observation and analysis of the simulations. A hematopoietic stem cell system is taken as reference case study for formulating a specific model and executing virtual experiments.

Funktionelle Analyse der onkologisch relevanten Protease Threonin-Aspartase 1

Krebs stellt eine der häufigsten Todesursachen in Europa dar. Grundlage für eine langfristige Verbesserung des Behandlungserfolgs ist ein molekulares Verständnis der Mechanismen, welche zur Krankheitsentstehung beitragen. In diesem Zusammenhang spielen Proteasen nicht nur eine wichtige Rolle, sondern stellen auch bei vielerlei Erkrankungen bereits anerkannte Zielstrukturen derzeitiger Behandlungsstrategien dar. Die Protease Threonin Aspartase 1 (Taspase1) spielt eine entscheidende Rolle bei der Aktivierung von Mixed Lineage Leukemia (MLL)-Fusionsproteinen und somit bei der Entstehung aggressiver Leukämien. Aktuelle Arbeiten unterstreichen zudem die onkologische Relevanz von Taspase1 auch für solide Tumore. Die Kenntnisse über die molekularen Mechanismen und Signalnetzwerke, welche für die (patho)biologischen Funktionen von Taspase1 verantwortlich sind, stellen sich allerdings noch immer als bruchstückhaft dar. Um diese bestehenden Wissenslücken zu schließen, sollten im Rahmen der Arbeit neue Strategien zur Inhibition von Taspase1 erarbeitet und bewertet werden. Zusätzlich sollten neue Einsichten in evolutionären Funktionsmechanismen sowie eine weitergehende Feinregulation von Taspase1 erlangt werden. Zum einen erlaubte die Etablierung und Anwendung eines zellbasierten Taspase1-Testsystem, chemische Verbindungen auf deren inhibitorische Aktivität zu testen. Überraschenderweise belegten solch zelluläre Analysen in Kombination mit in silico-Modellierungen eindeutig, dass ein in der Literatur postulierter Inhibitor in lebenden Tumorzellen keine spezifische Wirksamkeit gegenüber Taspase1 zeigte. Als mögliche Alternative wurden darüber hinaus Ansätze zur genetischen Inhibition evaluiert. Obwohl publizierte Studien Taspase1 als ααββ-Heterodimer beschreiben, konnte durch Überexpression katalytisch inaktiver Mutanten kein trans-dominant negativer Effekt und damit auch keine Inhibition des wildtypischen Enzyms beobachtet werden. Weiterführende zellbiologische und biochemische Analysen belegten erstmalig, dass Taspase1 in lebenden Zellen in der Tat hauptsächlich als Monomer und nicht als Dimer vorliegt. Die Identifizierung evolutionär konservierter bzw. divergenter Funktionsmechanismen lieferte bereits in der Vergangenheit wichtige Hinweise zur Inhibition verschiedenster krebsrelevanter Proteine. Da in Drosophila melanogaster die Existenz und funktionelle Konservierung eines Taspase1-Homologs postuliert wurde, wurde in einem weiteren Teil der vorliegenden Arbeit die evolutionäre Entwicklung der Drosophila Taspase1 (dTaspase1) untersucht. Obwohl Taspase1 als eine evolutionär stark konservierte Protease gilt, konnten wichtige Unterschiede zwischen beiden Orthologen festgestellt werden. Neben einem konservierten autokatalytischen Aktivierungsmechanismus besitzt dTaspase1 verglichen mit dem humanen Enzym eine flexiblere Substraterkennungs-sequenz, was zu einer Vergrößerung des Drosophila-spezifischen Degradoms führt. Diese Ergebnisse zeigen des Weiteren, dass zur Definition und Vorhersage des Degradoms nicht nur proteomische sondern auch zellbiologische und bioinformatische Untersuchungen geeignet und notwendig sind. Interessanterweise ist die differentielle Regulation der dTaspase1-Aktivität zudem auf eine veränderte intrazelluläre Lokalisation zurückzuführen. Das Fehlen von in Vertebraten hochkonservierten aktiven Kernimport- und nukleolären Lokalisationssignalen erklärt, weshalb dTaspase1 weniger effizient nukleäre Substrate prozessiert. Somit scheint die für die humane Taspase1 beschriebene Regulation von Lokalisation und Aktivität über eine Importin-α/NPM1-Achse erst im Laufe der Entwicklung der Vertebraten entstanden zu sein. Es konnte also ein bislang unbekanntes evolutionäres Prinzip identifiziert werden, über welches eine Protease einen Transport- bzw. Lokalisations-basierten Mechanismus zur Feinregulation ihrer Aktivität „von der Fliege zum Menschen“ nutzt. Eine weitere Möglichkeit zur dynamischen Funktionsmodulation bieten post-translationale Modifikationen (PTMs) der Proteinsequenz, zu welcher Phosphorylierung und Acetylierung zählen. Interessanterweise konnte für die humane Taspase1 über den Einsatz unabhängiger Methoden einschließlich massenspektrometrischer Analysen eine Acetylierung durch verschiedene Histon-Acetyltransferasen (HATs) nachgewiesen werden. Diese Modifikation erfolgt reversibel, wobei vor allem die Histon-Deacetylase HDAC1 durch Interaktion mit Taspase1 die Deacetylierung der Protease katalysiert. Während Taspase1 in ihrer aktiven Konformation acetyliert vorliegt, kommt es nach Deacetylierung zu einer Reduktion ihrer enzymatischen Aktivität. Somit scheint die Modulation der Taspase1-Aktivität nicht allein über intra-proteolytische Autoaktivierung, Transport- und Interaktionsmechanismen, sondern zudem durch post-translationale Modifikationen gesteuert zu werden. Zusammenfassend konnten im Rahmen dieser Arbeit entscheidende neue Einblicke in die (patho)biologische Funktion und Feinregulation der Taspase1 gewonnen werden. Diese Ergebnisse stellen nicht nur einen wichtigen Schritt in Richtung eines verbesserten Verständnis der „Taspase1-Biologie“, sondern auch zur erfolgreichen Inhibition und Bewertung der krebsrelevanten Funktion dieser Protease dar.

Planned complex suicide: Self-strangulation and plaster ingestion

The literature contains many case reports of planned and complex suicides, which combine various methods to commit suicide. In this article, we present the anomalous suicide of an adult male by strangulation with a belt and simultaneous ingestion of plaster. The specific circumstances of the case are described and relevant literature is briefly reviewed. This case vignette illustrates one example of the wide ranging methods employed in suicides and may represent the first reported case of a fatal complex suicide involving self-strangulation and plaster ingestion. Knowledge of varied and sometimes unusual suicide methods is important to the forensic investigator to prevent unnecessary criminal investigation and to reliably and confidently establish manner and cause of death.

Intravaginal practices, bacterial vaginosis, and HIV infection in women: individual participant data meta-analysis

Background Identifying modifiable factors that increase women's vulnerability to HIV is a critical step in developing effective female-initiated prevention interventions. The primary objective of this study was to pool individual participant data from prospective longitudinal studies to investigate the association between intravaginal practices and acquisition of HIV infection among women in sub-Saharan Africa. Secondary objectives were to investigate associations between intravaginal practices and disrupted vaginal flora; and between disrupted vaginal flora and HIV acquisition. Methods and Findings We conducted a meta-analysis of individual participant data from 13 prospective cohort studies involving 14,874 women, of whom 791 acquired HIV infection during 21,218 woman years of follow-up. Data were pooled using random-effects meta-analysis. The level of between-study heterogeneity was low in all analyses (I2 values 0.0%–16.1%). Intravaginal use of cloth or paper (pooled adjusted hazard ratio [aHR] 1.47, 95% confidence interval [CI] 1.18–1.83), insertion of products to dry or tighten the vagina (aHR 1.31, 95% CI 1.00–1.71), and intravaginal cleaning with soap (aHR 1.24, 95% CI 1.01–1.53) remained associated with HIV acquisition after controlling for age, marital status, and number of sex partners in the past 3 months. Intravaginal cleaning with soap was also associated with the development of intermediate vaginal flora and bacterial vaginosis in women with normal vaginal flora at baseline (pooled adjusted odds ratio [OR] 1.24, 95% CI 1.04–1.47). Use of cloth or paper was not associated with the development of disrupted vaginal flora. Intermediate vaginal flora and bacterial vaginosis were each associated with HIV acquisition in multivariable models when measured at baseline (aHR 1.54 and 1.69, p<0.001) or at the visit before the estimated date of HIV infection (aHR 1.41 and 1.53, p<0.001), respectively. Conclusions This study provides evidence to suggest that some intravaginal practices increase the risk of HIV acquisition but a direct causal pathway linking intravaginal cleaning with soap, disruption of vaginal flora, and HIV acquisition has not yet been demonstrated. More consistency in the definition and measurement of specific intravaginal practices is warranted so that the effects of specific intravaginal practices and products can be further elucidated.

Pacemakers and magnetic resonance imaging: Current status and survey in Switzerland

Electromagnetic fields arising from magnetic resonance imaging (MRI) can cause various clinically relevant functional disturbances in patients with cardiac pacemakers. Consequently, an implanted pacemaker is generally considered a contraindication for an MRI scan. With approximately 60 million MRI scans performed worldwide per year, MRI may be indicated for an estimated majority of pacemaker patients during the lifetime of their pacemakers. The availability of MR conditional pacemakers with CE labelling is of particular advantage since they allow the safe use of pacemakers in MRI. In this article the current state of knowledge on pacemakers and MR imaging is discussed. We present the results of a survey conducted among Swiss radiologists to assess current practice in patients with pacemakers.