I materiali ceramici trasparenti: preparazione, caratterizzazione e correlazione microstruttura-proprietà

This thesis focuses on the ceramic process for the production of optical grade transparent materials to be used as laser hosts. In order to be transparent a ceramic material must exhibit a very low concentration of defects. Defects are mainly represented by secondary or grain boundary phases and by residual pores. The strict control of the stoichiometry is mandatory to avoid the formation of secondary phases, whereas residual pores need to be below 150 ppm. In order to fulfill these requirements specific experimental conditions must be combined together. In addition powders need to be nanometric or at least sub-micrometric and extremely pure. On the other hand, nanometric powders aggregate easily and this leads to a poor, not homogeneous packing during shaping by pressing and to the formation of residual pores during sintering. Very fine powders are also difficult to handle and tend to absorb water on the surface. Finally, the powder manipulation (weighting operations, solvent removal, spray drying, shaping, etc), easily introduces impurities. All these features must be fully controlled in order to avoid the formation of defects that work as scattering sources thus decreasing the transparency of the material. The important role played by the processing on the transparency of ceramic materials is often underestimated. In the literature a high level of transparency has been reported by many authors but the description of the experimental process, in particular of the powder treatment and shaping, is seldom extensively described and important information that are necessary to reproduce the described results are often missing. The main goal of the present study therefore is to give additional information on the way the experimental features affect the microstructural evolution of YAG-based ceramics and thus the final properties, in particular transparency. Commercial powders are used to prepare YAG materials doped with Nd or Yb by reactive sintering under high vacuum. These dopants have been selected as the more appropriate for high energy and high peak power lasers. As far as it concerns the powder treatment, the thesis focuses on the influence of the solvent removal technique (rotavapor versus spray drying of suspensions in ethanol), the ball milling duration and speed, suspension concentration, solvent ratio, type and amount of dispersant. The influence of the powder type and process on the powder packing as well as the pressure conditions during shaping by pressing are also described. Finally calcination, sintering under high vacuum and in clean atmosphere, and post sintering cycles are studied and related to the final microstructure analyzed by SEM-EDS and HR-TEM, and to the optical and laser properties.

Topics in financial econometrics

In the first chapter, we consider the joint estimation of objective and risk-neutral parameters for SV option pricing models. We propose a strategy which exploits the information contained in large heterogeneous panels of options, and we apply it to S&P 500 index and index call options data. Our approach breaks the stochastic singularity between contemporaneous option prices by assuming that every observation is affected by measurement error. We evaluate the likelihood function by using a MC-IS strategy combined with a Particle Filter algorithm. The second chapter examines the impact of different categories of traders on market transactions. We estimate a model which takes into account traders’ identities at the transaction level, and we find that the stock prices follow the direction of institutional trading. These results are carried out with data from an anonymous market. To explain our estimates, we examine the informativeness of a wide set of market variables and we find that most of them are unambiguously significant to infer the identity of traders. The third chapter investigates the relationship between the categories of market traders and three definitions of financial durations. We consider trade, price and volume durations, and we adopt a Log-ACD model where we include information on traders at the transaction level. As to trade durations, we observe an increase of the trading frequency when informed traders and the liquidity provider intensify their presence in the market. For price and volume durations, we find the same effect to depend on the state of the market activity. The fourth chapter proposes a strategy to express order aggressiveness in quantitative terms. We consider a simultaneous equation model to examine price and volume aggressiveness at Euronext Paris, and we analyse the impact of a wide set of order book variables on the price-quantity decision.

Urban water demand model: the case study of Emilia Romagna (Italy)

Water is the driving force in nature. We use water for washing cars, doing laundry, cooking, taking a shower, but also to generate energy and electricity. Therefore water is a necessary product in our daily lives (USGS. Howard Perlman, 2013). The model that we created is based on the urban water demand computer model from the Pacific Institute (California). With this model we will forecast the future urban water use of Emilia Romagna up to the year of 2030. We will analyze the urban water demand in Emilia Romagna that includes the 9 provinces: Bologna, Ferrara, Forli-Cesena, Modena, Parma, Piacenza, Ravenna, Reggio Emilia and Rimini. The term urban water refers to the water used in cities and suburbs and in homes in the rural areas. This will include the residential, commercial, institutional and the industrial use. In this research, we will cover the water saving technologies that can help to save water for daily use. We will project what influence these technologies have to the urban water demand, and what it can mean for future urban water demands. The ongoing climate change can reduce the snowpack, and extreme floods or droughts in Italy. The changing climate and development patterns are expected to have a significant impact on water demand in the future. We will do this by conducting different scenario analyses, by combining different population projections, climate influence and water saving technologies. In addition, we will also conduct a sensitivity analyses. The several analyses will show us how future urban water demand is likely respond to changes in water conservation technologies, population, climate, water price and consumption. I hope the research can contribute to the insight of the reader’s thoughts and opinion.

Efficacia delle griglie in titanio con osso particolato nella ricostruzione dei difetti alveolari tridimensionali dei mascellari

Questa tesi valuta l’efficacia della tecnica delle griglie in titanio con osso particolato nella ricostruzione dei difetti alveolari tridimensionali ai fini della riabilitazione dentale implanto-protesica. Il primo studio ha considerato la metodica in termini di complicanze post-operatorie e di risultati implanto-protesici. Sono stati considerati 24 pazienti con difetti tridimensionali trattati con l’applicazione di 34 griglie di titanio e osso particolato e riabilitati protesicamente dopo circa 8-9 mesi. 4 su 34 griglie sono state rimosse prima dell’inserimento implantare (11.76% di fallimento totale); 20 su 34 griglie si sono esposte per deiscenza dei tessuti molli (58.82% di complicanze): 4 (11.77%) prima e 16 (47.05%) dopo le prime 4-6 settimane dall’intervento; in nessun caso il piano di trattamento implanto-protesico ha subito variazioni. Dopo un follow-up medio di 20 (3-48) mesi dal carico protesico, nessuno degli 88 impianti ha perso la propria osteo-integrazione (100% di sopravvivenza implantare), con un valore complessivo di successo implantare di 82.9%. Il secondo studio ha calcolato in termini volumetrici la ricostruzione ossea ottenuta con griglie e la sua corre-lazione con l’estensione dell’esposizione e la tempistica del suo verificarsi. Sono stati valutati 12 pazienti con 15 difetti alveolari. Per ciascun sito sono state studiate le immagini TC con un software dedicato per misurare i volumi in tre dimensioni: il volume di osso non formatosi rispetto a quanto pianificato, lacking bone volume (LBV), è stato calcolato sottraendo il volume di osso ricostruito, reconstructed bone volume (RBV) in fase di ri-entro chirurgico dal volume di osso pianificato pre-operativamente, planned bone volume (PBV). LBV è risultato direttamente proporzionale all’area di esposizione della griglia, con un valore del 16.3% di LBV per ogni cm2 di griglia esposta. Si sono evidenziate, inoltre, correlazioni positive tra LBV , la tempistica precoce di esposizione e il valore di PBV.

Untersuchungen zur Lebensweise und zur Populationskontrolle des Gemeinen Ohrwurms Forficula auricularia L. (Insecta, Dermaptera) in Rebanlagen

Der Gemeine Ohrwurm (Forficula auricularia LINNAEUS 1758) wurde bisher im Weinbau als natürlicher Gegenspieler verschiedener Rebschädlinge zu den Nützlingen gezählt. Etwa seit 2005 verursacht er aufgrund stark ansteigender Populationsdichten Schäden in pfälzischen Rebanlagen. Ohrwürmer halten sich massenhaft in den Trauben auf. Zusammen mit ihren Exkrementen geraten sie bei der Lese in großer Zahl ins Erntegut. Die Tiere werden von der weinbaulichen Praxis als sehr störend und qualitätsmindernd empfunden und ihre Einstufung als Nützling kritisch gesehen. Aufgrund dieser Problematik wurde im Mai 2007 ein durch den Forschungsring des Deutschen Weinbaus (FDW) finanziertes Forschungsprojekt am Dienstleistungszentrum Ländlicher Raum Rheinpfalz in Neustadt an der Weinstraße begonnen. Bis 2010 wurden offene Fragen zur Erfassung und Populationsbiologie des Gemeinen Ohrwurms in Rebanlagen bearbeitet, die von ihm verursachten Schäden beschrieben und Strategien zu seiner Befallsregulation entwickelt. Am Boden aktive Ohrwürmer wurden mit Bodenfallen nach BARBER (1931) aufgenommen. In der Laubwand des Rebstockes wurden die Ohrwürmer mit eigens konzipierten Bambusfallen erfasst. F. auricularia ist in pfälzischen Rebanlagen die dominierende Ohrwurm-Art. Im Projektverlauf wurde der univoltine Entwicklungszyklus des Gemeinen Ohrwurms in pfälzischen Rebanlagen vollständig aufgeklärt. In der Vegetationsperiode beeinflussten die Intensität der Bodenbewirtschaftung mit der resultierenden Flächenbegrünung, die Bodenart, die Lufttemperatur, die Luftfeuchtigkeit und die Niederschlagsmenge die Befallsdichten am Rebstock signifikant. Der Ohrwurm-Befall in den Trauben war signifikant von der Kompaktheit und vom Gewicht der Trauben sowie dem Fäulnisanteil pro Traube und von eingewachsenen Rebblättern in den Trauben abhängig. Das Überwinterungs- und Brutverhalten wurde durch die Art und Weise der Bodenbewirtschaftung beeinflusst beziehungsweise gestört.rnLabor- und Freilandversuche haben gezeigt, dass F. auricularia Pilzpathogene wie die Graufäule (Botrytis cinerea PERSOON 1794) und den Pinselschimmel (Penicillium crustosum THOM 1930) auf gesunde Trauben überträgt. Ferner haben Fraßversuche ergeben, dass der Ohrwurm nur faule und vorgeschädigte Beeren anfressen kann und keine intakten Beeren verletzt. Durch analytische und sensorische Untersuchungen wurde festgestellt, dass Ohrwurm-Kot sensorische Fehltöne im Wein verursachen kann. Diese werden durch das im Kot enthaltene 2-Methyl-1,4-benzochinon hervorgerufen, das eine Komponente des arteigenen Abwehrsekrets ist. Da sich der Ohrwurm jahreszeitlich bedingt entweder im Boden oder am Rebstock aufhält, wurden befallsregulierende Maßnahmen im Boden- und Laubwandbereich der Rebanlage durchgeführt. Durch Tiefengrubbern mit Umbruch der Begrünung im Herbst und Frühjahr wurden die überwinternden Imagines und die Gelege geschädigt, so dass in der darauf folgenden Vegetationsperiode die Befallsdichten in der Laubwand geringfügig aber nicht signifikant abnahmen. Die während der Aufwanderungsphase der Ohrwürmer Ende Juni durchgeführte mechanische Störung der Begrünung reduzierte den Ohrwurm-Befall am Rebstock bis zu drei Wochen nach der Maßnahme signifikant. In der Laubwand der Rebstöcke wurden die Befallsdichten durch die Insektizide SpinTor (Wirkstoff Spinosad: 0,01%) und Steward® (Wirkstoff Indoxacarb: 0,0125 %) sowie sekundär durch partielles Entblättern der Laubwand dauerhaft bis zur Traubenlese reduziert. rn

Synthese 18 F-markierter Liganden zur Visualisierung der GABA-Bindungsstelle des GABA A-Rezeptors mittels PET

γ-Aminobuttersäure (GABA) ist der wichtigste inhibitorische Neurotransmitter im zentralen Nervensystem und bindet vorrangig an ionotrope GABAA-Rezeptoren. Diese sind an fast allen neuronalen Prozessen beteiligt und werden darüber hinaus mit neurologischen Erkrankungen wie Epilepsie, Angstzuständen, Schlafstörungen und Schizophrenie in Verbindung gebracht. Die PET bietet als molekulares bildgebendes Verfahren die Möglichkeit einzelne Stoffwechselvorgänge des GABAergen Systems zu visualisieren und zu quantifizieren. Durch den Einsatz eines 18F-markierten Radioliganden an die GABA-Bindungsstelle könnten so die Rezeptorverfügbarkeit des GABAA-Rezeptors gemessen und die Ausschüttung des Neurotransmitters GABA quantifiziert werden.rn4-(2-Naphthylmethyl)-5-(piperidin-4-yl)isothiazolole und -isoxazolole stellen aufgrund ihrer hohen Affinität gegenüber der GABA-Bindungsstelle und ihrer lipophilen Struktur vielversprechende Leitstrukturen für die Entwicklung eines PET-Tracers zur Visualisierung der GABA-Bindungsstelle dar. Daher wurden zunächst 19F-substituierte Referenzverbindungen synthetisiert, um diese hinsichtlich ihrer Eignung als Radioligand in in vitro-Studien zu evaluieren. Dazu wurde Fluor direkt sowie über eine Fluorethoxygruppe an Position 1 des Naphthalinrings eingeführt. Zusätzlich wurde ein Fluorethylether eines Isothiazolols als Referenz-verbindung synthetisiert. In anschließenden Verdrängungsstudien wurden die Affinitäten der synthetisierten Verbindungen mit [3H]Muscimol an Membranpräparaten aus Rattenhirnen, sowie transfizierten HEK293-Zellen bestimmt. Zusätzlich wurden die entsprechenden Log D-Werte bestimmt. Die Verbindung 5-(piperidin-4-yl)-4-(1-fluornaphth-2-ylmethyl)-isothiazol-3-ol VK5 zeigte in den in vitro-Studien die vielversprechendsten Ergebnisse (IC50 = 10 nM; Log D = 1,7) und wurde im Folgenden in einer dreistufigen Radiosynthese als 18F-Verbindung synthetisiert.rnZu diesem Zweck wurde ein geeigneter Markierungsvorläufer dargestellt und über eine n.c.a. SNAr-Markierung mit [18F]F- umgesetzt. Die Reaktionsparameter wurden hinsichtlich Reaktionszeit, -temperatur, Basenkonzentration und Lösungsmittel optimiert. Die zur Aktivierung einer SNAr ein-geführte Carbonylfunktion wurde in einem zweiten Schritt mit Triethylsilan/Trifluoressigsäure reduziert. Im finalen Schritt wurden zwei Schutzgruppen mit Bortrichlorid in DCM abgespaltet und [18F]VK5 als injektionsfertige Lösung in isotoner NaCl-Lösung erhalten. Es wurden radiochemische Ausbeuten von 0,7-1 % (EOS) nach einer durchschnittlichen Synthesedauer von 275 Minuten erhalten.rnDer Radioligand [18F]VK5 wurde anschließend in Autoradiographie-Versuchen an Hirnschnitten der Ratte hinsichtlich seiner Spezifität für die GABA-Bindungsstelle untersucht. Die unspezifische Bindung wurde durch die Zugabe von GABA bestimmt wonach kein signifikanter Unterschied festgestellt werden konnte. Die hohe unspezifische Bindung kann möglicherweise auf die niedrigen spezifischen Aktivitäten zurückgeführt werden. Diese lagen, bedingt durch die drei Schritte der Radiosynthese, in einem Bereich von 0,1-0,6 GBq/μmol. Die erhaltenen Ergebnisse lassen für zukünftige Versuche noch einige Optimierungsmöglichkeiten offen. Aufgrund der bisher erhaltenen Daten lässt sich daher keine definitive Aussage über die Eignung des Liganden [18F]VK5 als PET-Tracer treffen.rn

Liquid crystalline cellulose derivatives for mirrorless lasing

In this thesis cholesteric films made of liquid crystalline cellulose derivatives with improved optical properties were prepared. The choice of the solvent, hydrogen bond influencing additives, the synthetic realization of a very high degree of substitution on the cellulosic polymer and the use of mechanical stirring at the upper concentration limit of the liquid crystalline range were the basis for an improved alignment of the applied cellulose tricarbamates. In combination with a tuned substrate treatment and film preparation method, cholesteric films were obtained, with optical properties that were theoretically predicted and only known from low molecular weight liquid crystals so far. Subsequent polymerization allowed a permanent fixing of the alignment and the fabrication of free standing and insensitive films.rnThe incorporation of inorganic nanorods into the cholesteric host material was mediated with tailored block copolymers, available via controlled radical polymerization methods. In addition to the shape match between the rodlike mesogens of the host and the nanorods it was possible to increase the miscibility of both materials. Nevertheless, the size of the nanorods, in comparison to the mesogens, in these densely packed liquid crystalline phases as well as their long equilibration times were the reasons for phase separation. Nanorods are, in principle, valuable substitutes for organics, but their utilization in cellulosic CLC was not to be combined with a high quality alignment of the cholesteric structure.rnA swelling process of polymerized films in a dye solution or dissolving dyes in non-polymerized CLC was used for incorporation of the organic chromophores. With the first method the CLC could be aligned and polymerized without any disturbance due to dye molecules. The optical properties of dye and CLC were matched, with regard to mirrorless lasing devices. The dye was optically excited and laser emission supported by the cholesteric cavity was obtained. The polarization and wavelength of the emitted radiation as well as its bandwidth, the obtained interference pattern and threshold behavior of the emission proofed the feedback mechanism that was not believed to be realizable in liquid crystalline polymers. rnUtilization of a microfluidic co-flow injection device enabled us to transfer the properties of cellulosic CLC from the planar film shape to spherical micrometer sized particles. The pure material yielded particles with distorted mesogen alignment similar to films prepared by capillary flow. Dilution of the CLC with a solvent that migrated into the carrier phase during particle preparation provided the basis for particles with well ordered areas. rnAlthough cellulose derivatives were known for their liquid crystalline behavior for decades and synthesized in mass production, their application as feedback material was affected by bad optical properties. In comparison to low molar mass compounds, the low degree of order in the CLC phase was the cause. With the improved material, defined lasing emission was shown and characterized. Derivatives of cellulose are desirable materials, because, as a renewable resource, they are available in large amounts for a low price and need only simple derivatization reactions. The fabrication of CLC films with tunable lasing emission, for which this thesis can provide a starting point, is in good agreement with today's requirements of modern technology and its miniaturization.rn

Untersuchung der Auswirkungen verschiedener Variationsbereiche des differenziellen Lernens und Lehrens im weiten Sinn auf ausgewählte technische Grundfertigkeiten im Hallenhockey

Die Frage wie großmotorische Bewegungen gelernt werden beschäftigt nicht nur Sportler, Trainer und Sportlehrer sondern auch Ärzte und Physiotherapeuten. Die sportwissenschaftlichen Teildisziplinen Bewegungs- und Trainingswissenschaft versuchen diese Frage sowohl im Sinne der Grundlagenforschung (Wie funktioniert Bewegungslernen?) als auch hinsichtlich der praktischen Konsequenzen (Wie lehrt man Bewegungen?) zu beantworten. Innerhalb dieser Themenfelder existieren Modelle, die Bewegungslernen als gezielte und extern unterstützte Ausbildung zentralnervöser Bewegungsprogramme verstehen und solche, die Lernen als Selbstorganisationsprozess interpretieren. Letzteren ist das Differenzielle Lernen und Lehren (Schöllhorn, 1999) zuzuordnen, das die Notwendigkeit betont, Bewegungen durch die Steigerung der Variationen während der Aneignungsphase zu lernen und zu lehren. Durch eine Vielzahl an Variationen, so die Modellannahme, findet der Lernende ohne externe Vorgaben selbstorganisiert ein individuelles situatives Optimum. Die vorliegende Arbeit untersucht, welchen Einfluss Variationen verschiedener Art und Größe auf die Lern- und Aneignungsleistung großmotorischer Bewegungen haben und in wie fern personenübergreifende Optima existieren. In zwei Experimenten wird der Einfluss von räumlichen (Bewegungsausführung, Bewegungsergebnis) und zeitlichen Variationen (zeitliche Verteilung der Trainingsreize) auf die Aneignungs- und Lernleistung großmotorischer sportlicher Bewegungen am Beispiel zweier technischer Grundfertigkeiten des Hallenhockeys untersucht. Die Ergebnisse der Experimente stützen die bisherige Befundlage zum Differenziellen Lernen und Lehren, wonach eine Zunahme an Variation in der Aneignungsphase zu größeren Aneignungs- und Lernleistungen führt. Zusätzlich wird die Annahme bestätigt, dass ein Zusammenhang von Variationsbereich und Lernrate in Form eines Optimaltrends vorliegt. Neu sind die Hinweise auf die Dynamik von motorischen Lernprozessen (Experiment 1). Hier scheinen individuelle Faktoren (z. B. die Lernbiografie) als auch die Phase im Lernprozess (Aneignung, Lernen) Einfluss zu haben auf den Umfang und die Struktur eines für die optimale Adaptation notwendigen Variationsbereichs. Darüber hinaus weisen die Befunde auf verschiedene Aneignungs- und Lerneffekte aufgrund alleiniger Variation der zeitlichen Verteilung bei ansonsten gleichen Trainingsreizen hin (Experiment 2). Für zukünftige Forschungsarbeiten zum Erlernen großmotorischer Bewegungen und für die sportliche Praxis dürfte es daher erkenntnisreich sein, die Historie der intrinsischen Dynamik der lernenden Systeme stärker zu berücksichtigen. Neben Fragestellungen für die Grundlagenforschung zum (Bewegungs-)Lernen ließen sich hieraus unmittelbar praxisrelevante Erkenntnisse darüber ableiten, wie Bewegungslernprozesse mittels verschiedener Variationsbereiche strukturiert und gesteuert werden könnten.

Selective photo-oxidation of glucose

Biomass transformation into high-value chemicals has attracted attention according to the “green chemistry” principles. Low price and high availability make biomass one of the most interesting renewable resources as it provides the means to create sustainable alternatives to the oil-derived building blocks of the chemical industry In recent year, the need for alternative environmentally friendly routes to drive chemical reactions has in photocatalytic processes an interesting way to obtain valuable chemicals from various sources using the solar light as energy source. The purpose of this work was to use supported noble metal nanoparticles in the selective photo-oxidation of glucose through using visible light. Glucose was chosen as model molecule because it is the cheapest and the most common monosaccharide. Few studies about glucose photo oxidation have been conducted so far, and reaction mechanism is still not totally explained. The aim of this work was to systematically analyze and assess the impact of several parameters (eg. catalyst/substrate ratio, reaction time, effect of the solvent and light source) on the reaction pathway and to monitor the product distribution in order to draw a general reaction scheme for the photo oxidation of glucose under visible light. This study regards the reaction mechanism and the influence of several parameters, such as solvent, light power and substrate concentration. Furthermore, the work focuses on the influence of gold and silver nanoparticles and on the influence of metal loading. The glucose oxidation was monitored through the mass balance and the products selectivity. Reactions were evaluated in terms of glucose conversion, mass balance and selectivities towards arabinose and gluconic acid. In conclusion, this study is able to demonstrate that the photo oxidation of glucose under visible light is feasible; the full identification of the main products allows, for the first time, a comprehensive reaction mechanism scheme.

Suitability of low-dosage oxytocin treatment to induce milk ejection in dairy cows

Chronic use of high oxytocin (OT) dosages can cause a reduced response to endogenous OT. In this study the OT dosages used in the milking practice of 82 dairy cow farms were recorded. The OT dosages per cow used were high, especially when injected i.m. (23+/-2 IU) compared with i.v. (7+/-1 IU). In addition, the minimum OT dosages needed to obtain normal milk removal in cows with disturbed milk ejection were investigated. Seventeen cows routinely treated with OT during milking (group T) and 17 cows without previous OT treatment were used (group C). After cessation of spontaneous milk flow, both T and C groups were injected i.v. with a low dosage of OT (0.2 or 0.5 IU/cow). The time from injection until cessation of the OT-induced milk flow was recorded (response phase). The response phase and the amounts of removed milk by effect of the OT injection increased with increasing OT dosage. Values for 0.2 and 0.5 IU/cow of OT injected i.v. were (response phase and amount of milk removed) 198+/-27 and 302+/-18s and 3.4+/-0.7 kg and 6.5+/-1.3 kg, respectively, for the C group, and 157+/-15 and 221+/-16s and 3.2+/-0.5 and 5.5+/-1.0 kg, respectively, for the T group. Within 20 min of the OT injection, plasma concentrations returned to basal levels. The threshold OT concentration at cessation of milk flow after injection of 0.2 or 0.5 IU/cow of OT was calculated based on the OT plasma half-life. The threshold increased with increasing dosages of OT and was higher in group T (8+/-1 and 14+/-1 pg/mL for 0.2 and 0.5 IU/cow, respectively) than in group C (7+/-1 and 11+/-1 pg/mL for 0.2 and 0.5 IU/cow, respectively). In conclusion, desensitization of the udder toward OT occurs when the udder is exposed to elevated OT plasma concentrations, both short-term during the actual milking and long-term due to chronic high-dosage OT treatment. However, low-dosage OT treatments to induce normal milk removal can minimize the observed side effects.

CD4-guided scheduled treatment interruptions compared with continuous therapy for patients infected with HIV-1: results of the Staccato randomised trial

BACKGROUND: Stopping antiretroviral therapy in patients with HIV-1 infection can reduce costs and side-effects, but carries the risk of increased immune suppression and emergence of resistance. METHODS: 430 patients with CD4-positive T-lymphocyte (CD4) counts greater than 350 cells per muL, and viral load less than 50 copies per mL were randomised to continued therapy (n=146) or scheduled treatment interruptions (n=284). Median time on randomised treatment was 21.9 months (range 16.4-25.3). Primary endpoints were proportion of patients with viral load less than 50 copies per mL at the end of the trial, and amount of drugs used. Analysis was intention-to-treat. This study is registered at ClinicalTrials.gov with the identifier NCT00113126. FINDINGS: Drug savings in the scheduled treatment interruption group, compared with continuous treatment, amounted to 61.5%. 257 of 284 (90.5%) patients in the scheduled treatment interruption group reached a viral load less than 50 copies per mL, compared with 134 of 146 (91.8%) in the continued treatment group (difference 1.3%, 95% CI-4.3 to 6.9, p=0.90). No AIDS-defining events occurred. Diarrhoea and neuropathy were more frequent with continuous treatment; candidiasis was more frequent with scheduled treatment interruption. Ten patients (2.3%) had resistance mutations, with no significant differences between groups. INTERPRETATION: Drug savings with scheduled treatment interruption were substantial, and no evidence of increased treatment resistance emerged. Treatment-related adverse events were more frequent with continuous treatment, but low CD4 counts and minor manifestations of HIV infection were more frequent with scheduled treatment interruption.

Characterization of retinal damage in the episcleral vein cauterization rat glaucoma model

Episcleral vein cauterization (EVC) is used in rats to generate a glaucoma model with high intraocular pressure (IOP). The long-term retinal damage in this glaucoma model, however, has not been accurately quantified. We report the location and amount of retinal ganglion cell (RGC) damage caused by (EVC) induced IOP elevation in two rat strains. IOP was raised in one eye of Wistar (N = 5) and Brown-Norway(B-N)(N = 7) rats by EVC and monitored monthly until IOP in contralateral eyes equalized at 5 months post-surgery. Animals were maintained for 3.5-4.5 additional months. B-N rats (N = 7) that had no EVC served as controls for this strain. Scotopic flash ERGs were recorded at baseline and just prior to euthanasia. Automated counts of all retrogradely labeled RGCs in retinal flat-mounts were determined and compared between contralateral eyes. RGC density maps were constructed and RGC size distribution was determined. Oscillatory potentials in the group of eyes which had elevated IOP were decreased at the time of euthanasia, when IOP had returned to normal. The group of normal B-N rats had similar RGC counts between contralateral eyes. In the experimental group the mean number of RGCs was not significantly different between control and experimental eyes, but 1 of 5 Wistar and 2 of 7 B-N experimental eyes had at least 30% fewer RGCs than contralateral control eyes. Total retinal area in B-N experimental eyes was higher compared to contralateral eyes. Cumulative IOP exposure of the experimental eyes was modestly correlated with RGC loss while oscillatory potentials appeared to be inversely related to RGC loss. In retinas with extensive (> 30% RGC loss) but not complete damage, smaller cells were preserved better than larger ones. The above results indicate that RGC loss in both Wistar and B-N strains is variable after a prolonged elevation of IOP via EVC. Such variability despite equivalent IOP levels and ERG abnormalities, suggests unknown factors that can protect IOP-stressed RGCs. Identification and enhancement of such factors could prove useful for glaucoma therapy.

Comparison of analgesic efficacy of preoperative or postoperative carprofen with or without preincisional mepivacaine epidural anesthesia in canine pelvic or femoral fracture repair

OBJECTIVE: To compare analgesic efficacy of preoperative versus postoperative administration of carprofen and to determine, if preincisional mepivacaine epidural anesthesia improves postoperative analgesia in dogs treated with carprofen. STUDY DESIGN: Blind, randomized clinical study. ANIMALS: Dogs with femoral (n=18) or pelvic (27) fractures. METHODS: Dogs were grouped by restricted randomization into 4 groups: group 1 = carprofen (4 mg/kg subcutaneously) immediately before induction of anesthesia, no epidural anesthesia; group 2 = carprofen immediately after extubation, no epidural anesthesia; group 3 = carprofen immediately before induction, mepivacaine epidural block 15 minutes before surgical incision; and group 4 = mepivacaine epidural block 15 minutes before surgical incision, carprofen after extubation. All dogs were administered carprofen (4 mg/kg, subcutaneously, once daily) for 4 days after surgery. Physiologic variables, nociceptive threshold, lameness score, pain, and sedation (numerical rating scale [NRS], visual analog scale [VAS]), plasma glucose and cortisol concentration, renal function, and hemostatic variables were measured preoperatively and at various times after surgery. Dogs with VAS pain scores >30 were administered rescue analgesia. RESULTS: Group 3 and 4 dogs had significantly lower pain scores and amount of rescue analgesia compared with groups 1 and 2. VAS and NRS pain scores were not significantly different among groups 1 and 2 or among groups 3 and 4. There was no treatment effect on renal function and hemostatic variables. CONCLUSIONS: Preoperative carprofen combined with mepivacaine epidural anesthesia had superior postoperative analgesia compared with preoperative carprofen alone. When preoperative epidural anesthesia was performed, preoperative administration of carprofen did not improve postoperative analgesia compared with postoperative administration of carprofen. CLINICAL RELEVANCE: Preoperative administration of systemic opioid agonists in combination with regional anesthesia and postoperative administration of carprofen provides safe and effective pain relieve in canine fracture repair.

Adequacy of an early arterial phase low-volume contrast protocol in 64-detector computed tomography angiography for aortoiliac aneurysms

PURPOSE: This retrospective study was conducted to determine whether a low-volume contrast medium protocol provides sufficient enhancement for 64-detector computed tomography angiography (CTA) in patients with aortoiliac aneurysms. METHODS: Evaluated were 45 consecutive patients (6 women; mean age, 72 +/- 6 years) who were referred for aortoiliac computed tomography angiography between October 2005 and January 2007. Group A (22 patients; creatinine clearance, 64.2 +/- 8.1 mL/min) received 50 mL of the contrast agent. Group B (23 patients; creatinine clearance, 89.4 +/- 7.3 mL/min) received 100 mL of the contrast agent. The injection rate was 3.5 mL/s, followed by 30 mL of saline at 3.5 mL/s. Studies were performed on the same 64-detector computed tomography scanner using a real-time bolus-tracking technique. Quantitative analysis was performed by determination of mean vascular attenuation at 10 regions of interest from the suprarenal aorta to the common femoral artery by one reader blinded to type and amount of contrast agent and compared using the Student t test. Image quality according to a 4-point scale was assessed in consensus by two readers blinded to type and amount of contrast medium and compared using the Mann-Whitney test. Multivariable adjustments were performed using ordinal regression analysis. RESULTS: Mean total attenuation did not differ significantly between both groups (196.5 +/- 33.0 Hounsfield unit [HU] in group A and 203.1 +/- 44.2 HU in group B; P = .57 by univariate and P > .05 by multivariable analysis). Accordingly, attenuation at each region of interest was not significantly different (P > .35). Image quality was excellent or good in all patients. No significant differences in visual assessment were found comparing both contrast medium protocols (P > .05 by univariate and by multivariable analysis). CONCLUSIONS: Aortoiliac aneurysm imaging can be performed with substantially reduced amounts of contrast medium using 64-detector computed tomography angiography technology.

Quantum modeling of bioconjugated nanomaterials

In recent years, the bio-conjugated nanostructured materials have emerged as a new class of materials for the bio-sensing and medical diagnostics applications. In spite of their multi-directional applications, interfacing nanomaterials with bio-molecules has been a challenge due to somewhat limited knowledge about the underlying physics and chemistry behind these interactions and also for the complexity of biomolecules. The main objective of this dissertation is to provide such a detailed knowledge on bioconjugated nanomaterials toward their applications in designing the next generation of sensing devices. Specifically, we investigate the changes in the electronic properties of a boron nitride nanotube (BNNT) due to the adsorption of different bio-molecules, ranging from neutral (DNA/RNA nucleobases) to polar (amino acid molecules). BNNT is a typical member of III-V compounds semiconductors with morphology similar to that of carbon nanotubes (CNTs) but with its own distinct properties. More specifically, the natural affinity of BNNTs toward living cells with no apparent toxicity instigates the applications of BNNTs in drug delivery and cell therapy. Our results predict that the adsorption of DNA/RNA nucleobases on BNNTs amounts to different degrees of modulation in the band gap of BNNTs, which can be exploited for distinguishing these nucleobases from each other. Interestingly, for the polar amino acid molecules, the nature of interaction appeared to vary ranging from Coulombic, van der Waals and covalent depending on the polarity of the individual molecules, each with a different binding strength and amount of charge transfer involved in the interaction. The strong binding of amino acid molecules on the BNNTs explains the observed protein wrapping onto BNNTs without any linkers, unlike carbon nanotubes (CNTs). Additionally, the widely varying binding energies corresponding to different amino acid molecules toward BNNTs indicate to the suitability of BNNTs for the biosensing applications, as compared to the metallic CNTs. The calculated I-V characteristics in these bioconjugated nanotubes predict notable changes in the conductivity of BNNTs due to the physisorption of DNA/RNA nucleobases. This is not the case with metallic CNTs whose transport properties remained unaltered in their conjugated systems with the nucleobases. Collectively, the bioconjugated BNNTs are found to be an excellent system for the next generation sensing devices.