Impact of fractionation on out-of-field survival and DNA damage responses following exposure to intensity modulated radiation fields

To limit toxicity to normal tissues adjacent to the target tumour volume, radiotherapy is delivered using fractionated regimes whereby the total prescribed dose is given as a series of sequential smaller doses separated by specific time intervals. The impact of fractionation on out-of-field survival and DNA damage responses was determined in AGO-1522 primary human fibroblasts and MCF-7 breast tumour cells using uniform and modulated exposures delivered using a 225 kVp x-ray source. Responses to fractionated schedules (two equal fractions delivered with time intervals from 4 h to 48 h) were compared to those following acute exposures. Cell survival and DNA damage repair measurements indicate that cellular responses to fractionated non-uniform exposures differ from those seen in uniform exposures for the investigated cell lines. Specifically, there is a consistent lack of repair observed in the out-of-field populations during intervals between fractions, confirming the importance of cell signalling to out-of-field responses in a fractionated radiation schedule, and this needs to be confirmed for a wider range of cell lines and conditions.

A box in the field: modernity and the barn in twentieth-century Ireland

This paper argues that the modern barn in Ireland is a complex social and architectural phenomena that is without, or has yet to find, a satisfactory discourse. Emerging in the middle third of the twentieth century, the modern barn – replete with corrugated iron and I-sections – continues to represent a presence in the Irish landscape whose ubiquity is as emphatic as its flexibility. It is, however, its universal properties that begin to suggest connections with wider narratives. The modernising aspects of the barn that appear in the 1920s and 30s begin to conflate with a rhetoric of architectural modernism which was simultaneously appearing across Europe. But while the relationship between high modernism’s critique of what it divined as the inspirational qualities of utilitarian buildings – Walter Gropius on grain silos, Le Corbusier on aircraft hangers etc. – has been well-documented, in Ireland this relationship perhaps contains another layer of complexity.
The barn’s consolidation as a modern type coincided with the search for a nation’s cultural identity after centuries of colonial rule. This tended to be an introspective vision that prioritised rural space over urban space, agriculture over industry, and imagined the small farm as a central tenet in the construction of a new State. This paper suggests that the twentieth-century barn – as a product of the mechanisation of agriculture promoted by the new administrations – is an iconic structure, emblematic of attempts to reconcile the contradictory forces and imagery of modernity with the mores of a traditional society. Moreover, given a cultural purview that was often ambivalent or even hostile to the ideologies and forms of modernity, the barn in Ireland is, perhaps, not so much the inspiration but the realisation of an architectural modernism in that country at its most pervasive, enduring and unself-conscious.

Geographical variation in inorganic arsenic in paddy field samples and commercial rice from the Iberian Peninsula

This study investigated total arsenic and arsenic speciation in rice using ion chromatography with mass spectrometric detection (IC-ICP-MS), covering the main rice-growing regions of the Iberian Peninsula in Europe. The main arsenic species found were inorganic and dimethylarsinic acid. Samples surveyed were soil, shoots and field-collected rice grain. From this information soil to plant arsenic transfer was investigated plus the distribution of arsenic in rice across the geographical regions of Spain and Portugal. Commercial polished rice was also obtained from each region and tested for arsenic speciation, showing a positive correlation with field-obtained rice grain. Commercial polished rice had the lowest i-As content in Andalucia, Murcia and Valencia while Extremadura had the highest concentrations. About 26% of commercial rice samples exceeded the permissible concentration
for infant food production as governed by the European Commission. Some cadmium data is also presented, available with ICP-MS analyses, and show low concentration in rice samples.

Perceptual user interface framework for immersive information retrieval environments (An experimental framework for testing and rapid iteration)

The use of perceptual inputs is an emerging area within HCI that suggests a developing Perceptual User Interface (PUI) that may prove advantageous for those involved in mobile serious games and immersive social network environments. Since there are a large variety of input devices, software platforms, possible interactions, and myriad ways to combine all of the above elements in pursuit of a PUI, we propose in this paper a basic experimental framework that will be able to standardize study of the wide range of interactive applications for testing efficacy in learning or information retrieval and also suggest improvements to emerging PUIs by enabling quick iteration. This rapid iteration will start to define a targeted range of interactions that will be intuitive and comfortable as perceptual inputs, and enhance learning and information retention in comparison to traditional GUI systems. The work focuses on the planning of the technical development of two scenarios, and the first steps in developing a framework to evaluate these and other PUIs for efficacy and pedagogy.

Building 3D City Models: Testing and Comparing Laser Scanning and Low-Cost UAV Data Using FOSS Technologies

Contém resumo

NEW METHODS FOR DETECTION, SUSCEPTIBILITY TESTING AND BIOFILM ERADICATION OF DIFFICULT ORGANISMS

Aujourd'hui, les problèmes des maladies infectieuses concernent l'émergence d'infections difficiles à traiter, telles que les infections associées aux implants et les infections fongiques invasives chez les patients immunodéprimés. L'objectif de cette thèse était de développer des stratégies pour l'éradication des biofilms bactériens (partie 1), ainsi que d'étudier des méthodes innovantes pour la détection microbienne, pour l'établissement de nouveaux tests de sensibilité (partie 2). Le traitement des infections associées aux implants est difficile car les biofilms bactériens peuvent résister à des niveaux élevés d'antibiotiques. A ce jour, il n'y a pas de traitement optimal défini contre des infections causées par des bactéries de prévalence moindre telles que Enterococcus faecalis ou Propionibacterium acnés. Dans un premier temps, nous avons démontré une excellente activité in vitro de la gentamicine sur une souche de E. faecalis en phase stationnaire de croissance Nous avons ensuite confirmé l'activité de la gentamicine sur un biofilm précoce en modèle expérimental animal à corps étranger avec un taux de guérison de 50%. De plus, les courbes de bactéricidie ainsi que les résultats de calorimétrie ont prouvé que l'ajout de gentamicine améliorait l'activité in vitro de la daptomycine, ainsi que celle de la vancomycine. In vivo, le schéma thérapeutique le plus efficace était l'association daptomycine/gentamicine avec un taux de guérison de 55%. En établissant une nouvelle méthode pour l'évaluation de l'activité des antimicrobiens vis-à-vis de micro-organismes en biofilm, nous avons démontré que le meilleur antibiotique actif sur les biofilms à P. acnés était la rifampicine, suivi par la penicilline G, la daptomycine et la ceftriaxone. Les études conduites en modèle expérimental animal ont confirmé l'activité de la rifampicine seule avec un taux de guérison 36%. Le meilleur schéma thérapeutique était au final l'association rifampicine/daptomycine avec un taux de guérison 63%. Les associations de rifampicine avec la vancomycine ou la levofloxacine présentaient des taux de guérisons respectivement de 46% et 25%. Nous avons ensuite étudié l'émergence in vitro de la résistance à la rifampicine chez P. acnés. Nous avons observé un taux de mutations de 10"9. La caractérisation moléculaire de la résistance chez les mutant-résistants a mis en évidence l'implication de 5 mutations ponctuelles dans les domaines I et II du gène rpoB. Ce type de mutations a déjà été décrit au préalable chez d'autres espèces bactériennes, corroborant ainsi la validité de nos résultats. La deuxième partie de cette thèse décrit une nouvelle méthode d'évaluation de l'efficacité des antifongiques basée sur des mesures de microcalorimétrie isotherme. En utilisant un microcalorimètre, la chaleur produite par la croissance microbienne peut être-mesurée en temps réel, très précisément. Nous avons évalué l'activité de l'amphotéricine B, des triazolés et des échinocandines sur différentes souches de Aspergillus spp. par microcalorimétrie. La présence d'amphotéricine Β ou de triazole retardait la production de chaleur de manière concentration-dépendante. En revanche, pour les échinochandines, seule une diminution le pic de « flux de chaleur » a été observé. La concordance entre la concentration minimale inhibitrice de chaleur (CMIC) et la CMI ou CEM (définie par CLSI M38A), avec une marge de 2 dilutions, était de 90% pour l'amphotéricine B, 100% pour le voriconazole, 90% pour le pozoconazole et 70% pour la caspofongine. La méthode a été utilisée pour définir la sensibilité aux antifongiques pour d'autres types de champignons filamenteux. Par détermination microcalorimétrique, l'amphotéricine B s'est avéré être l'agent le plus actif contre les Mucorales et les Fusarium spp.. et le voriconazole le plus actif contre les Scedosporium spp. Finalement, nous avons évalué l'activité d'associations d'antifongiques vis-à-vis de Aspergillus spp. Une meilleure activité antifongique était retrouvée avec l'amphotéricine B ou le voriconazole lorsque ces derniers étaient associés aux échinocandines vis-à-vis de A. fumigatus. L'association échinocandine/amphotéricine B a démontré une activité antifongique synergique vis-à-vis de A. terreus, contrairement à l'association échinocandine/voriconazole qui ne démontrait aucune amélioration significative de l'activité antifongique. - The diagnosis and treatment of infectious diseases are today increasingly challenged by the emergence of difficult-to-manage situations, such as infections associated with medical devices and invasive fungal infections, especially in immunocompromised patients. The aim of this thesis was to address these challenges by developing new strategies for eradication of biofilms of difficult-to-treat microorganisms (treatment, part 1) and investigating innovative methods for microbial detection and antimicrobial susceptibility testing (diagnosis, part 2). The first part of the thesis investigates antimicrobial treatment strategies for infections caused by two less investigated microorganisms, Enterococcus faecalis and Propionibacterium acnes, which are important pathogens causing implant-associated infections. The treatment of implant-associated infections is difficult in general due to reduced susceptibility of bacteria when present in biofilms. We demonstrated an excellent in vitro activity of gentamicin against E. faecalis in stationary growth- phase and were able to confirm the activity against "young" biofilms (3 hours) in an experimental foreign-body infection model (cure rate 50%). The addition of gentamicin improved the activity of daptomycin and vancomycin in vitro, as determined by time-kill curves and microcalorimetry. In vivo, the most efficient combination regimen was daptomycin plus gentamicin (cure rate 55%). Despite a short duration of infection, the cure rates were low, highlighting that enterococcal biofilms remain difficult to treat despite administration of newer antibiotics, such as daptomycin. By establishing a novel in vitro assay for evaluation of anti-biofilm activity (microcalorimetry), we demonstrated that rifampin was the most active antimicrobial against P. acnes biofilms, followed by penicillin G, daptomycin and ceftriaxone. In animal studies we confirmed the anti-biofilm activity of rifampin (cure rate 36% when administered alone), as well as in combination with daptomycin (cure rate 63%), whereas in combination with vancomycin or levofloxacin it showed lower cure rates (46% and 25%, respectively). We further investigated the emergence of rifampin resistance in P. acnes in vitro. Rifampin resistance progressively emerged during exposure to rifampin, if the bacterial concentration was high (108 cfu/ml) with a mutation rate of 10"9. In resistant isolates, five point mutations of the rpoB gene were found in cluster I and II, as previously described for staphylococci and other bacterial species. The second part of the thesis describes a novel real-time method for evaluation of antifungals against molds, based on measurements of the growth-related heat production by isothermal microcalorimetry. Current methods for evaluation of antifungal agents against molds, have several limitations, especially when combinations of antifungals are investigated. We evaluated the activity of amphotericin B, triazoles (voriconazole, posaconazole) and echinocandins (caspofungin and anidulafungin) against Aspergillus spp. by microcalorimetry. The presence of amphotericin Β or a triazole delayed the heat production in a concentration-dependent manner and the minimal heat inhibition concentration (MHIC) was determined as the lowest concentration inhibiting 50% of the heat produced at 48 h. Due to the different mechanism of action echinocandins, the MHIC for this antifungal class was determined as the lowest concentration lowering the heat-flow peak with 50%. Agreement within two 2-fold dilutions between MHIC and MIC or MEC (determined by CLSI M38A) was 90% for amphotericin B, 100% for voriconazole, 90% for posaconazole and 70% for caspofungin. We further evaluated our assay for antifungal susceptibility testing of non-Aspergillus molds. As determined by microcalorimetry, amphotericin Β was the most active agent against Mucorales and Fusarium spp., whereas voriconazole was the most active agent against Scedosporium spp. Finally, we evaluated the activity of antifungal combinations against Aspergillus spp. Against A. jumigatus, an improved activity of amphotericin Β and voriconazole was observed when combined with an echinocandin. Against A. terreus, an echinocandin showed a synergistic activity with amphotericin B, whereas in combination with voriconazole, no considerable improved activity was observed.

Statistical hypothesis testing and common misinterpretations: should we abandon p-value in forensic science applications?

Many people regard the concept of hypothesis testing as fundamental to inferential statistics. Various schools of thought, in particular frequentist and Bayesian, have promoted radically different solutions for taking a decision about the plausibility of competing hypotheses. Comprehensive philosophical comparisons about their advantages and drawbacks are widely available and continue to span over large debates in the literature. More recently, controversial discussion was initiated by an editorial decision of a scientific journal [1] to refuse any paper submitted for publication containing null hypothesis testing procedures. Since the large majority of papers published in forensic journals propose the evaluation of statistical evidence based on the so called p-values, it is of interest to expose the discussion of this journal's decision within the forensic science community. This paper aims to provide forensic science researchers with a primer on the main concepts and their implications for making informed methodological choices.

Report from the annual meeting of the shareholders held on June 1, 1886 in which amendments and field rules and regulations were made

Report from the annual meeting of the shareholders held on June 1, 1886 in which amendments and field rules and regulations were made (copy of 1 handwritten page). This is signed by Louis N. Hayne, secretary, June 7, 1886.

Telling the truth about HIV? Testing and disclosure in a culture of stigma

Étude de cas / Case study

Spanning avalanches in the three-dimensional Gaussian random-field Ising model with metastable dynamics: Field dependence and geometrical properties

Spanning avalanches in the 3D Gaussian Random Field Ising Model (3D-GRFIM) with metastable dynamics at T=0 have been studied. Statistical analysis of the field values for which avalanches occur has enabled a Finite-Size Scaling (FSS) study of the avalanche density to be performed. Furthermore, a direct measurement of the geometrical properties of the avalanches has confirmed an earlier hypothesis that several types of spanning avalanches with two different fractal dimensions coexist at the critical point. We finally compare the phase diagram of the 3D-GRFIM with metastable dynamics with the same model in equilibrium at T=0.

Programming Principles: Testing and Debugging

In this session we look at the sorts of errors that occur in programs, and how we can use different testing and debugging strategies (such as unit testing and inspection) to track them down. We also look at error handling within the program and at how we can use Exceptions to manage errors in a more sophisticated way. These slides are based on Chapter 6 of the Book 'Objects First with BlueJ'

Development of chemical separation processes for the treatment and monitoring of metallic cations and oxoanions in polluted waters

The chemical contamination of natural waters is a global problem with a worldwide impact. Considering the relevance of this problem, this thesis is intended, on one hand, to develop different separation/preconcentration techniques based on membranes ability to permeate anions for the transport of toxic oxyanions of chromium(VI) and arsenic contained in aqueous matrices. In particular, we have investigated supported liquid membranes and polymer inclusion membranes, both of which contain the commercial quaternary ammonium salt Aliquat 336 as a carrier, as well as commercial anion exchange membranes. On the other hand, we have focused on the development of chemical sensors to facilitate the monitoring of several metals from different aqueous matrices. Thus, a selective optical sensor for Cr(VI) based on polymeric membranes containing Aliquat 336 as an ionophore has been designed. Additionally, mercury-based screen-printed electrodes have been evaluated for for cadmium, lead, copper and zinc detection.

Historical review of articulation testing and a recent revision of auditory test no. 9

This paper reviews the history of articulation testing and presents a revision of a standard articulation test.

A literature review of three common balance tests: Electronystagmography, Rotary Chair Testing, and Computerized Dynamic Posturography

This paper discusses the rationale, clinical applications, advantages and disadvantages of three common balance function tests: Electronystagmography (ENG), Rotational Chair Testing (RCT), and Computerized Dynamic Posturography (CDP).