A New Technique for Studying Vapour–liquid Equilibria of Multi-Component Systems

A Fourier transform infrared gas-phase method is described herein and capable of deriving the vapour pressure of each pure component of a poorly volatile mixture and determining the relative vapour phase composition for each system. The performance of the present method has been validated using two standards (naphthalene and ferrocene), and a Raoult’s plot surface of a ternary system is reported as proof-of-principle. This technique is ideal for studying solutions comprising two, three, or more organic compounds dissolved in ionic liquids as they have no measurable vapour pressures.

Sjuksköterskans stöd till personer med psykiska funktionsnedsättningar i utövandet av fysisk aktivitet och dess hälsoeffekter Litteraturstudie

Det har forskats mycket om fysisk aktivitets positiva effekter på människokroppen rent fysiskt. Tidigare har det inte varit en naturlig del av behandlingen inom psykiatrin vilket gjorde författarna nyfikna på hur det kan lyftas fram i vården av personer med psykiska funktionsnedsättningar. Syfte: Syftet med litteraturstudien var att beskriva hälsoeffekterna av fysisk aktivitet för personer med psykiska funktionsnedsättningar och sjuksköterskans stöd genom handledning. Metod: Litteraturstudie. Resultat: Under sammanställningen av resultatet framkom att sjuksköterskor kan ge stöd genom Motiverande samtal (MI) som var av central betydelse. Då patienten själv hörsammas och bygger upp sina mål som ska vara mätbara tillsammans med utbildad vårdpersonal, men även genom stöd i patienternas egen utbildning och kunskap av den fysiska aktivitetens positiva inverkan på psykisk ohälsa. Slutsats: Sjuksköterskans metod att stödja och motivera personer med psykiska funktionsnedsättningar till att utöva fysisk aktivitet visade sig vara flera. Då det var viktigt med personcentrarad metod, var viktigt att de behärskade och kände till olika vägar att kunna motivera personer med psykiska funktionsnedsättningar. Andra betydelsefulla tillvägagångssätt var god vårdrelation, individualiserade träningsprogram, samt stöd och utbildning i de positiva hälsoeffekterna som fysisk aktivitet gav.

¿Neurodidáctica aplicada? : Una investigación sobre las aplicaciones de la neurodidáctica en la enseñanza de español y en concreto en el libro de texto Caminando 3.

This thesis analyzes the teaching material Caminando 3 from a neurodidactic perspective. The discipline of neurodidactics is young and controversial and the aim of this investigation is to present an understanding of the use of practical applications of neurodidactics in written material of education in Spanish as a second language. The methods applied are a quantitative and objective analysis of measurable aspects in Caminando 3 and a qualitative, subjective analysis which is interpreting fundamental understandings of language learning which Caminando 3 reflects in its structure and content. The results show that there are several aspects in Caminando 3 which are supported by the evidences and advices of the neurodidactic theories and simultaneously there are details in exercises and parts of the layup containing a level of repetition and prediction which are directly harmful to the process of acquisition, according to neurodidactic theories. The conclusion is that a more dynamic teaching book can be produced with guidelines that can be created using these results. Further investigations will have to measure the knowledge and success of the pupils to decide whether neurodidactics is a successful complement to traditional didactics of second language learning.

CURB-65 and Other Markers of Illness Severity in Community-Acquired Pneumonia Among HIV-Positive Patients

As the relative burden of community-acquired bacterial pneumonia among HIV-positive patients increases, adequate prediction of case severity on presentation is crucial. We sought to determine what characteristics measurable on presentation are predictive of worse outcomes. We studied all admissions for community-acquired bacterial pneumonia over one year at a tertiary centre. Patient demographics, comorbidities, HIV-specific markers and CURB-65 scores on Emergency Department presentation were reviewed. Outcomes of interest included mortality, bacteraemia, intensive care unit admission and orotracheal intubation. A total of 396 patients were included: 49 HIV-positive and 347 HIV-negative. Mean CURB-65 score was 1.3 for HIV-positive and 2.2 for HIV-negative patients (p < 0.0001), its predictive value for mortality being maintained in both groups (p = 0.03 and p < 0.001, respectively). Adjusting for CURB-65 scores, HIV infection by itself was only associated with bacteraemia (adjusted odds ratio [AOR] 7.1, 95% CI [2.6-19.5]). Patients with < 200 CD4 cells/µL presented similar CURB-65 adjusted mortality (aOR 1.7, 95% CI [0.2-15.2]), but higher risk of intensive care unit admission (aOR 5.7, 95% CI [1.5-22.0]) and orotracheal intubation (aOR 9.1, 95% CI [2.2-37.1]), compared to HIV-negative patients. These two associations were not observed in the > 200 CD4 cells/µL subgroup (aOR 2.2, 95% CI [0.7-7.6] and aOR 0.8, 95% CI [0.1-6.5], respectively). Antiretroviral therapy and viral load suppression were not associated with different outcomes (p > 0.05). High CURB-65 scores and CD4 counts < 200 cells/µL were both associated with worse outcomes. Severity assessment scales and CD4 counts may both be helpful in predicting severity in HIV-positive patients presenting with community-acquired bacterial pneumonia.

Kultur ist mehr als Currywurst Ältere Literatur im Deutschunterricht : Eine Literaturstudie

With regards to the teaching of German in Sweden this literature study looks into the Swedish curriculum and the CEFR (Common European Framework of Reference for Languages) to compare today’s common interpretation of the goals in language learning to the educational goals in the documents. Critics mean that the CEFR and in extension the curricula in the associated countries focus mainly on measurable practical language skills. This leads to impoverishment of the concept of language learning, which should include broad cultural aspects, encourage the students to develop their personalities and curiosity and foster a livelong desire to study. This work will try to show that blaming the CEFR for the kind of lopsided development towards practical, measurable skills in language teaching does not origin in the document or in the national curriculum. It appears to be the interpretation of the documents that oversees some essential requirements, not only for successful language teaching but also for the use of German as a tool for conversation and understanding. The real understanding of a language is, according to the research referred to in this work, connected to the understanding of culture. This literature study will show that reading older literature in language classes will favour the students´ understanding of culture. Furthermore, this work will try to point out other educational benefits besides the gain of cultural knowledge in working with literature. Students learn to argue and gain understanding of their own world by comparing to the new reality they meet in the literature. In addition, students will, with the help of the text, acquire new vocabulary and get an understanding of the structure of the language. In essence the use of literature in teaching German on one hand meets and fulfils the requirements in the curriculum and on the other hand supports the development of language skills and personals skills.

Failure Mechanisms and Local Scour at Coastal Structures induced by Tsunamis

On March 11 2011, an exceptionally large tsunami event was triggered by a massive earthquake offshore, the northeast coast of Japan, which affected coastal infrastructure such as seawalls, coastal dikes and breakwaters in the Tohoku region. Such infrastructure was built to protect against the Level 1 tsunamis that previously hit the region, but not for events as significant as the 2011 Tohoku tsunami, which was categorized as a Level 2 tsunami [Shibayama et al. 2013]. The failure mechanisms of concrete-armoured dikes, breakwaters and seawalls due to Level 2 tsunamis are still not fully understood by researchers and engineers. This paper investigates the failure modes and mechanisms of damaged coastal structures in Miyagi and Fukushima Prefectures, following the authors' post-disaster field surveys carried out between 2011 and 2013. Six significant failure mechanisms were identified for the coastal dikes and seawalls affected by this tsunami: 1) Leeward toe scour failure, 2) Crown armour failure, 3) Leeward slope armour failure, 4) Seaward toe and armour failure, 5) Overturning failure, and 6) Parapet wall failure, in which leeward toe scour being recognized as the major failure mechanism in most surveyed locations. The authors also propose a simple practical mathematical model for predicting the scour depth at the leeward toe of the coastal dikes, by considering the effects of the tsunami hydrodynamics, the soil properties and the type of structure. The key advantage of this model is that it depends entirely on quantities that are measurable in the field. Furthermore this model was further refined by conducting a series of hydraulic model experiments aimed to understand the governing factors of the leeward toe scour failure. Finally, based on the results obtained, key recommendations are given for the design of resilient coastal defence structures that can survive a level 2 tsunami event.

Princípios Lean aplicados à gestão da informação: um caso prático no departamento de custeio da ECCO

O pensamento lean, assim como os conceitos e práticas que lhe estão associados, são, hoje em dia, vistos pelas organizações como meios que promovem a busca pela excelência empresarial. A aplicação dos princípios lean ultrapassou já a barreira do domínio produtivo, conhecendo-se, cada vez mais, outros ramos de utilização, como é o caso do setor dos serviços, que tem demonstrado um potencial enorme no que diz respeito à exploração desta filosofia. No entanto, as experiências de aplicação destes princípios a outras áreas, que não a indústria de transformação, têm ainda poucos resultados concretos espelhados na literatura. Este projeto surge no sentido de contribuir para alcançar processos mais eficientes, aplicando ferramentas e metodologias da filosofia lean a processos de gestão da informação, tendo o caso prático decorrido no recém-criado Departamento de Custeio Global da ECCO. Por se tratar de um novo departamento, ergue-se a necessidade de construir e modificar ferramentas e práticas em toda a estrutura da empresa. Deste modo, o lean será utilizado como um possível caminho para promover a melhoria contínua dos vários processos, tendo em vista a obtenção de uma melhor relação entre os resultados obtidos e os recursos despendidos. Assim, serão apresentadas várias propostas de melhoria para o departamento em causa, no âmbito da gestão da informação e que, partindo de uma análise inicial baseada nos princípios lean, pretendem agregar mais valor aos processos, minimizando os desperdícios que lhes estão associados e, consequentemente, promovendo o seu melhoramento contínuo.

Évaluation de la performance des drains et des matériaux filtrants à ralentir le colmatage et l’ensablement en sol sableux et ferreux

Au Québec, les drains installés dans les sols sableux-limoneux sont sensibles au colmatage par ensablement et/ou par ocre de fer. Dans le passé, les drains avec des pertuis inférieurs à 2 mm étaient utilisés au Québec avec un filtre tissé de 110 microns ou un filtre tricoté de 450 microns. Récemment, des drains avec des pertuis supérieurs à 2 mm ainsi qu’un filtre de 250 microns ont été introduits sur le marché mais n’ont jamais été testés. Le projet avait pour objectif de déterminer les vitesses auxquelles se feront l’ensablement et le colmatage ferrique pour différentes combinaisons de drains (pertuis de 1,8 mm et de 3 mm) et de filtres (110 μm, 250 μm et 450 μm) dans un sol sableux à Bécancour. Un dispositif expérimental en blocs complets (3) aléatoires a été utilisé. Les débits ont été mesurés à la sortie des drains de chaque parcelle et les hauteurs des nappes ont été mesurées avec un bulleur dans des puits d’observation. Le suivi du pH, du potentiel d’oxydoréduction et du contenu en Fe2+ a été réalisé dans l’eau de la nappe et celle des drains. Les drains excavés 13 mois après leur installation ne montrent que des traces de sédiments et de colmatage ferrique. Les niveaux de Fe2+ sont significativement plus faibles dans l’eau à la sortie des drains que dans l’eau de la nappe. Le processus de colmatage ferrique ne semble que commencer et son impact n’est pas mesurable au niveau des débits unitaires à la sortie des drains.

Relating Innovative 2D Ideas into 3D Garments in Terms of Structure, Using ‘Sculptural Form Giving’ as an Intermediate Step in Creation.

This research focuses on finding a fashion design methodology to reliably translate innovative two-dimensional ideas on paper, via a structural design sculpture, into an intermediate model. The author, both as a fashion designer and a researcher, has witnessed the issues which arise, regarding the loss of some of the initial ideas and distortion during the two-dimensional creative sketch to three-dimensional garment transfer process. Therefore, this research is concerned with fashion designers engaged in transferring a two-dimensional sketch through the method ‘sculptural form giving’. This research method applies the ideal model of conceptual sculpture, in the fashion design process, akin to those used in the disciplines of architecture. These parallel design disciplines share similar processes for realizing design ideas. Moreover, this research investigates and formalizes the processes that utilize the measurable space between the garment and the body, to help transfer garment variation and scale. In summation, this research proposition focuses on helping fashion designers to produce a creative method that helps the designer transfer their imaginative concept through intermediate modeling.

Käytettävyyssuunnittelun teoria ja käytäntö: Tapaustutkimus huonekalujen verkkokaupasta

Käytettävien ohjelmistojen suunnittelu tuo hyötyjä loppukäyttäjälle sekä muille sidosryhmille. Verkkokaupassa käytettävyys on elintärkeää, koska asiakkaat vaihtavat helposti seuraavalle sivustolle, mikäli he eivät löydä etsimäänsä. Tutkimusten mukaan käytettävyys vaikuttaa ostopäätöksen tekemiseen. Lisäksi käytettävyydellä on merkitystä asiakastyytyväisyyteen, joka taas vaikuttaa asiakasuskollisuuteen. Tässä tutkielmassa tutkittiin, miten käytettävyyttä suunnitellaan käytännössä verrattuna teoreettisiin suosituksiin. Tapaustutkimuksen kohteena oli huonekaluja myyvän kansainvälisen yrityksen verkkokaupan uudistamiseen tähtäävä projekti. Uudistamistarve nousi aikaisemman verkkokauppaversion puutteellisesta käytettävyydestä. Projekti toteutettiin ketterällä Scrum-menetelmällä. Empiirinen aineisto kerättiin puolistrukturoitujen haastattelujen avulla. Haastateltavat olivat käyttökokemuksen suunnitteluun osallistuvia henkilöitä. Haastattelujen teemat laadittiin teoreettisen aineiston pohjalta. Teoreettisessa osuudessa tutkittiin käytettävyyden suunnitteluun liittyviä periaatteita, prosessia ja menetelmiä. Aikaisemmasta tutkimuksesta löydettiin 12 periaatetta, jotka tukevat ja luonnehtivat käyttäjäkeskeistä suunnittelua. Käytettävyyttä suunnitellaan käyttäjäkeskeisen prosessin avulla. Eri prosessimallit pitivät keskeisinä asioina käyttökontekstin määrittelyä ja ymmärtämistä, mitattavia käytettävyysvaatimuksia, suunnitteluratkaisujen empiiristä arviointia sekä suunnitteluprosessin iteratiivisuutta. Lisäksi tarkasteltiin, mitä suunnittelumenetelmiä tutkijat ehdottavat käytettävyyden suunnitteluun ja mitä kyselytutkimusten perusteella todellisuudessa käytetään. Verkkokauppaprojektissa käytettävyyden suunnittelu erosi osittain teoreettisista suosituksista. Käyttökontekstitietoa ei ollut kaikilla projektiin osallistuvilla, eikä käytettävyysvaatimuksia ollut asetettu teorian tarkoittamalla tavalla. Yhtäläisyyksiäkin löytyi. Verkkokauppaprojektissa suunnitteluratkaisuja arvioitiin empiirisesti todellisten käyttäjien edustajien avulla. Suunnitteluprosessi oli iteratiivinen eli suunnitteluratkaisuja oltiin valmiita muuttamaan arvioinnin tuloksena. Tutkimuksen perusteella suositellaan, että verkkokauppaprojektissa parannettaisiin kommunikointia, koska käyttökontekstitieto ei saavuttanut kaikkia projektissa työskenteleviä. Teorian tulisi entisestään korostaa kommunikoinnin tärkeyttä. Tutkimuksen perusteella esitetään myös, että teoria ohjaisi paremmin vaatimusmäärittelyjen tekemiseen käytännössä. Avainsanat: Käytettävyys, käyttäjäkeskeinen suunnittelu, käytettävyyden periaatteet, käytettävyyden suunnittelumenetelmät, ketterä ohjelmistokehitys, tapaustutkimus

Investigation on reproduction process in two species of crab Eriphia sebana and Ocypode saratan in the intertidal zone of Chabahar area

The present study with headline investigation on reproduction in two species of Crab Eriphia sebana and Ocypode saratan was carried out in the intertidal zone of Chabahar in thirteen month from December 2004 to December 2005. Checked samplings have been taken, 45 number Crab monthly from any four stations by manual or use trap. During this study the following subjects were measured: Temperature range and salinity, Measurable coast granule, Determination of sex ratio, Relations carapace width with carapace length, Carapace width with total body weight, Gonad weight, gonadosomatic index, condition factor, gastrosomatic index, investigation content in stomach, LM50, Growth parameters, plenty distribution length and width and gonad weight and total body weight. Studied on measurable coast granule were expressed that Ocypode saratan in Desalination station, were nest in soils equable sand and this quantity were confirmed in Pozm station. Sex ratio were assign in desalination area and Pozm M: F 0/44:0/56 and in Tiss and Chabahar M: F 0/45:0/55. Carapace length and carapace width (cm) and body weight (g) Furthest were designated in Ocypode saratan within carapace width sequential: female: 5/42-6/15-105/13 and male: 5/53-6/25-108/91 and in Eriphia sebana within Tiss area sequential: female: 5/12-5/94-110/21 and male 5/14-60/01-114/37. Have been linear relationship between carapace length and carapace width and equaled CW = a CL + b. Weight growth in two species were be modal and equaled BW= aCLb and increased Crab weight by built up carapace width. Maximum gonad weight in Ocypode saratan within desalination area in female have been outcome 3/39 and in male 0/84g and in Eriphia sebana extreme within Tiss during may in female were be 4/18 and in male 1/1g. Stomach content in Eriphia sebana were involved a black until half-purplish liquid and yellowish in Ocypode saratan. Stomach contents identifiable were being in four groups: Molluscoid, Crustacean, Plankton and Fish. Carapace width during the first year of maturation have been LM50:3/77 in Desalination area and LM50:3/92 in Pozm for Ocypode saratan and LM50:4/26 in Tiss and LM50:4/62 in Chabahar. Ability spawning in Eriphia sebana within Tiss has been CW=4/17cm and in Ocypode saratan within Desalination area CW=4/23cm. Maximun value of Loo for Eriphia sebana was equal 59/67 and growth factor K=0/68 within Tiss and Loo =61/64 , K=0/65 for Ocypode saratan within Desalination area. Maximun GSI and GI have been within Desalination area and Tiss and minimum within Pozm and Chabahar. The maturity stages of two species were classifed into six stages. Review on GSI, CF have been showed that relation with temperature and salinity and definer in two species have been spawned in two period that Maximun in spring premier than autumn.

Effect of boiling on deposition of metallic colloids

In this study the relationship between heterogeneous nucleate boiling surfaces and deposition of suspended metallic colloidal particles, popularly known as crud or corrosion products in process industries, on those heterogeneous sites is investigated. Various researchers have reported that hematite is a major constituent of crud which makes it the primary material of interest; however the models developed in this work are irrespective of material choice. Qualitative hypotheses on the deposition process under boiling as proposed by previous researchers have been tested, which fail to provide explanations for several physical mechanisms observed and analyzed. In this study a quantitative model of deposition rate has been developed on the basis of bubble dynamics and colloid-surface interaction potential. Boiling from a heating surface aids in aggregation of the metallic particulates viz. nano-particles, crud particulate, etc. suspended in a liquid, which helps in transporting them to heating surfaces. Consequently, clusters of particles deposit onto the heating surfaces due to various interactive forces, resulting in formation of porous or impervious layers. The deposit layer grows or recedes depending upon variations in interparticle and surface forces, fluid shear, fluid chemistry, etc. This deposit layer in turn affects the rate of bubble generation, formation of porous chimneys, critical heat flux (CHF) of surfaces, activation and deactivation of nucleation sites on the heating surfaces. Several problems are posed due to the effect of boiling on colloidal deposition, which range from research initiatives involving nano-fluids as a heat transfer medium to industrial applications such as light water nuclear reactors. In this study, it is attempted to integrate colloid and surface science with vapor bubble dynamics, boiling heat transfer and evaporation rate. Pool boiling experiments with dilute metallic colloids have been conducted to investigate several parameters impacting the system. The experimental data available in the literature is obtained by flow experiments, which do not help in correlating boiling mechanism with the deposition amount or structure. With the help of experimental evidences and analysis, previously proposed hypothesis for particle transport to the contact line due to hydrophobicity has been challenged. The experimental observations suggest that deposition occurs around the bubble surface contact line and extends underneath area of the bubble microlayer as well. During the evaporation the concentration gradient of a non-volatile species is created, which induces osmotic pressure. The osmotic pressure developed inside the microlayer draws more particles inside the microlayer region or towards contact line. The colloidal escape time is slower than the evaporation time, which leads to the aggregation of particles in the evaporating micro-layer. These aggregated particles deposit onto or are removed from the heating surface, depending upon their total interaction potential. Interaction potential has been computed with the help of surface charge and van der Waals potential for the materials in aqueous solutions. Based upon the interaction-force boundary layer thickness, which is governed by debye radius (or ionic concentration and pH), a simplified quantitative model for the attachment kinetics is proposed. This attachment kinetics model gives reasonable results in predicting attachment rate against data reported by previous researchers. The attachment kinetics study has been done for different pH levels and particle sizes for hematite particles. Quantification of colloidal transport under boiling scenarios is done with the help of overall average evaporation rates because generally waiting times for bubbles at the same position is much larger than growth times. In other words, from a larger measurable scale perspective, frequency of bubbles dictates the rate of collection of particles rather than evaporation rate during micro-layer evaporation of one bubble. The combination of attachment kinetics and colloidal transport kinetics has been used to make a consolidated model for prediction of the amount of deposition and is validated with the help of high fidelity experimental data. In an attempt to understand and explain boiling characteristics, high speed visualization of bubble dynamics from a single artificial large cavity and multiple naturally occurring cavities is conducted. A bubble growth and departure dynamics model is developed for artificial active sites and is validated with the experimental data. The variation of bubble departure diameter with wall temperature is analyzed with experimental results and shows coherence with earlier studies. However, deposit traces after boiling experiments show that bubble contact diameter is essential to predict bubble departure dynamics, which has been ignored previously by various researchers. The relationship between porosity of colloid deposits and bubbles under the influence of Jakob number, sub-cooling and particle size has been developed. This also can be further utilized in variational wettability of the surface. Designing porous surfaces can having vast range of applications varying from high wettability, such as high critical heat flux boilers, to low wettability, such as efficient condensers.

Soft tissue sarcoma: biology and therapeutic correlates

Soft tissue sarcomas (STS) comprise a heterogenenous group of greater than 50 malignancies of putative mesenchymal cell origin and as such they may arise in diverse tissue types in various anatomical locations throughout the whole body. Collectively they account for approximately 1% of all human malignancies yet have a spectrum of aggressive behaviours amongst their subtypes. They thus pose a particular challenge to manage and remain an under investigated group of cancers with no generally applicable new therapies in the past 40 years and an overall 5-year survival rate that remains stagnant at around 50%. From September 2000 to July 2006 I undertook a full time post-doctoral level research fellowship at the MD Anderson Cancer Center, Houston, Texas, USA in the department of Surgical Oncology to investigate the biology of soft tissue sarcoma and test novel anti- sarcoma adenovirus-based therapy in the preclinical nude rat model of isolated limb perfusion against human sarcoma xenografts. This work, in collaboration with colleagues as indicated herein, led to a number of publications in the scientific literature furthering our understanding of the malignant phenotype of sarcoma and reported preclinical studies with wild-type p53, in a replication deficient adenovirus vector, and oncolytic adenoviruses administered by isolated limb perfusion. Additional collaborative and pioneering preclinical studies reported the molecular imaging of sarcoma response to systemically delivered therapeutic phage RGD-4c AAVP. Doxorubicin chemotherapy is the single most active broadly applicable anti-sarcoma chemotherapeutic yet only has an approximate 30% overall response rate with additional breakthrough tumour progression and recurrence after initial chemo-responsiveness further problematic features in STS management. Doxorubicin is a substrate for the multi- drug resistance (mdr) gene product p-glycoprotein drug efflux pump and exerts its main mode of action by induction of DNA double-strand breaks during the S-phase of the cell cycle. Two papers in my thesis characterise different aspects of chemoresistance in sarcoma. The first shows that wild-type p53 suppresses Protein Kinase Calpha (PKCα) phosphorylation (and activation) of p-glycoprotein by transcriptional repression of PKCα through a Sp-1 transcription factor binding site in its -244/-234 promoter region. The second paper demonstrates that Rad51 (a central mediator of homologous recombination repair of double strand breaks) has elevated levels in sarcoma and particularly in the S- G2 phase of the cell cycle. Suppression of Rad51 with small interfering RNA in sarcoma cell culture led to doxorubicin chemosensitisation. Reintroduction of wild-type p53 into STS cell lines resulted in decreased Rad51 protein and mRNA expression via transcriptional repression of the Rad51 promoter through increased AP-2 binding. In light of poor response rates to chemotherapy, escape from local control portends a poor prognosis for patients with sarcoma. Two papers in my thesis characterise aspects of sarcoma angiogenesis, invasion and metastasis. Human sarcoma samples were found to have high levels of matrix metalloproteinase-9 (MMP-9) with expression levels that correlated with p53 mutational status. MMP-9 is known to degrade extracellular collagen, contribute to the control of the angiogenic switch necessary in primary tumour progression and facilitate invasion and metastasis. Reconstitution of wild-type p53 function led to decreased levels of MMP-9 protein and mRNA as well as zymography-assessed MMP-9 proteolytic activity and decreased tumour cell invasiveness. Reintroduction of wild-type p53 into human sarcoma xenografts in-vivo decreased tumour growth and MMP-9 protein expression. Wild-type p53 was found to suppress mmp-9 transcription via decreased binding of NF-κB to its -607/-595 mmp-9 promoter element. Studies on the role of the VEGF165 in sarcoma found that sarcoma cells stably transfected with VEGF165 formed more aggressive xenografted tumours with increased vascularity, growth rate, metastasis, and resistance to chemotherapy. Use of the anti-VEGFR2 antibody DC101 enhanced doxorubicin sensitivity at sub-conventional dosing, inhibited tumour growth, decreased development of metastases, and reduced tumour micro-vessel density while increasing the vessel maturation index. These effects were explained primarily through effects on endothelial cells (e.c.s), rather than the tumour cells per se, where DC101 induced e.c. sensitivity to doxorubicin and suppressed e.c. production of MMPs. The p53 tumour suppressor pathway is the most frequently mutated pathway in sarcoma. Recapitulation of wild-type p53 function in sarcoma exerts a number of anti-cancer outcomes such as growth arrest, resensitisation to chemotherapy, suppression of invasion, and attenuation of angiogenesis. Using a modified nude rat-human sarcoma xenograft model for isolated limb perfusion (ILP) delivery of wild-type p53 in a replication deficient adenovirus vector I showed that functionally competent wild-type p53 could be delivered to and detected in human leiomyosarcoma xenografts confirming preclinical feasibility - although not efficacious due to low transgene expression. Viral fibre modification to express the RGD tripeptide motif led to greater viral uptake by sarcoma cells in vitro (transductional targeting) and changing the transgene promoter to a response element active in cells with active telomerase expression restricted the transgene expression to the tumour intracellular environment (transcriptional targeting). Delivery of the fibre-modified, selectively replication proficient oncolytic adenovirus Ad.hTC.GFP/ E1a.RGD by ILP demonstrated a more robust, and tumour-restricted, transgene expression with evidence of anti-sarcoma effect confirmed microscopically. Collaborative studies using the fibre modified phage RGD-4C AAVP confirmed that systemic delivery specifically, efficiently, and repeatedly targets human sarcoma xenografts, binds to αv integrins in tumours, and demonstrates a durable, though heterogeneous, transgene expression of 1-4 weeks. Incorporation of the Herpes Simplex Virus thymidine kinase (HSVtk) transgene into RGD-4C AAVP permitted CT-PET spatial and temporal molecular imaging in vivo of transgene expression and allowed quantification of tumour metabolic activity both before and after interval administration of a systemic cytotoxic with predictable and measurable response to treatment before becoming apparent clinically. These papers further the medical and scientific community’s understanding of the biology of soft tissue sarcoma and report preclinical studies with novel and promising anti- sarcoma therapeutics.

Volunteering for the Commonwealth Games: what can realist synthesis contribute to health policy making?

The aim of this thesis was to investigate, using the real-time test case of the 2014 Commonwealth Games, whether the realist synthesis methodology could contribute to the making of health policy in a meaningful way. This was done by looking at two distinct research questions: first, whether realist synthesis could contribute new insights to the health policymaking process, and second, whether the 2014 Commonwealth Games volunteer programme was likely to have any significant, measurable, impact on health inequalities experienced by large sections of the host population. The 2014 Commonwealth Games legacy laid out ambitious plans for the event, in which it was anticipated that it would provide explicit opportunities to impact positively on health inequalities. By using realist synthesis to unpick the theories underpinning the volunteer programme, the review identifies the population subgroups for whom the programme was likely to be successful, how this could be achieved and in what contexts. In answer to the first research question, the review found that while realist methods were able to provide a more nuanced exposition of the impacts of the Games volunteer programme on health inequalities than previous traditional reviews had been able to provide, there were several drawbacks to using the method. It was found to be resource-intensive and complex, encouraging the exploration of a much wider set of literatures at the expense of an in-depth grasp of the complexities of those literatures. In answer to the second research question, the review found that the Games were, if anything, likely to exacerbate health inequalities because the programme was designed in such a way that individuals recruited to it were most likely to be those in least need of the additional mental and physical health benefits that Games volunteering was designed to provide. The following thesis details the approach taken to investigate both the realist approach to evidence synthesis and the likelihood that the 2014 Games volunteer programme would yield the expected results.

Post-shock thermochemistry in hypervelocity CO2 and air flow

This work represents ongoing efforts to study high-enthalpy carbon dioxide flows in anticipation of the upcoming Mars Science Laboratory (MSL) and future missions to the red planet. The work is motivated by observed anomalies between experimental and numerical studies in hypervelocity impulse facilities for high enthalpy carbon dioxide flows. In this work, experiments are conducted in the Hypervelocity Expansion Tube (HET) which, by virtue of its flow acceleration process, exhibits minimal freestream dissociation in comparison to reflected shock tunnels. This simplifies the comparison with computational result as freestream dissociation and considerable thermochemical excitation can be neglected. Shock shapes of the MSL aeroshell and spherical geometries are compared with numerical simulations incorporating detailed CO2 thermochemical modeling. The shock stand-off distance has been identified in the past as sensitive to the thermochemical state and as such, is used here as an experimental measurable for comparison with CFD and two different theoretical models. It is seen that models based upon binary scaling assumptions are not applicable for the low-density, small-scale conditions of the current work. Mars Science Laboratory shock shapes at zero angle of attack are also in good agreement with available data from the LENS X expansion tunnel facility, confi rming results are facility-independent for the same type of flow acceleration, and indicating that the flow velocity is a suitable first-order matching parameter for comparative testing. In an e ffort to address surface chemistry issues arising from high-enthalpy carbon dioxide ground-test based experiments, spherical stagnation point and aeroshell heat transfer distributions are also compared with simulation. Very good agreement between experiment and CFD is seen for all shock shapes and heat transfer distributions fall within the non-catalytic and super-catalytic solutions. We also examine spatial temperature profiles in the non-equilibrium relaxation region behind a stationary shock wave in a hypervelocity air Mach 7.42 freestream. The normal shock wave is established through a Mach reflection from an opposing wedge arrangement. Schlieren images confirm that the shock con guration is steady and the location is repeatable. Emission spectroscopy is used to identify dissociated species and to make vibrational temperature measurements using both the nitric oxide and the hydroxyl radical A-X band sequences. Temperature measurements are presented at selected locations behind the normal shock. LIFBASE is used as the simulation spectrum software for OH temperature-fitting, however the need to access higher vibrational and rotational levels for NO leads to the use of an in-house developed algorithm. For NO, results demonstrate the contribution of higher vibrational and rotational levels to the spectra at the conditions of this study. Very good agreement is achieved between the experimentally measured NO vibrational temperatures and calculations performed using an existing state-resolved, three-dimensional forced harmonic oscillator thermochemical model. The measured NO A-X vibrational temperatures are significantly higher than the OH A-X temperatures.