Healthcare facilities are dynamic, long-term investments that must be able to respond to change in order to avoid obsolescence. Flexibility is a response used in healthcare facility design and construction to counter uncertainties, such as changing medical technologies, medical science and regulations. Flexible infrastructure design offers healthcare facilities the opportunity to combat obsolescence stemming from uncertainties. Interstitial Building Space (IBS) is one of many flexible infrastructure design options that assists with both mid-range and long-term flexibility. IBS is an unfinished and unoccupied horizontal space between a building's floors, fully accessible to people for the purpose of service and maintenance. The advent of Evidence Based Design (EBD) introduced a new dimension to the already dynamic healthcare facility. "EBD represents a body of science that links elements of the built environment with patient, staff and resource outcomes" (Malone et al. 2007 p.5). The incorporation of EBD increases the complexity for the design and construction of healthcare facilities. A framework was developed that articulates the dependent relationships between flexibility, IBS and EBD. The framework is comprised of three key elements: 1) a comprehensive "IBS Spectrum of Benefits" matrix resulting from a systematic literature review 2) a "Flexibility-EBD Conceptual Model" illustrating the relationship between flexibility and EBD, while identifying a continuum of flexibility enabled by this relationship; and 3) a "IBS-EBD Component Mapping Framework" articulating direct matches between the "IBS Spectrum of Benefits" and EBD components. The framework and the key elements within provide a foundational resource for stakeholders and researchers alike, navigating the interrelated intricacies associated with flexibility, EBD and IBS. / Master of Science / Healthcare facilities are dynamic, long-term investments that must be able to respond to change in order to avoid obsolescence. Flexibility is one response which enables facilities to combat changes and/ or uncertainties. This thesis explores the relationships between flexibility, Interstitial Building Space and Evidence Based Design, documents each relationship, and depicts their interrelated nature with the establishment of an overarching framework.

Heterogeneous catalysis is a key industrial process involved in the synthesis of nearly all chemicals currently produced. The environmental impact of these processes is huge so improvements must be made to current catalysts. Should a new material provide better yields at lower energy cost the benefits to both the industry and the planet are significant. There are many ways to change the behaviour of a catalyst, the addition of dopants, the selective blocking of active sites, and changing the strength of the support interaction to name a few. One technique that has become increasingly investigated is interstitial modification, the insertion of a light element into a metal lattice to change the metal's catalytic properties. The work presented in this thesis devises greener synthetic routes to the known Pd-^interstitialB/C catalyst and investigates potential routes to a novel interstitial material, Pd-^interstitialLi/C. Initially, successful verification of interstitial modification comes from the characteristic increase in palladium lattice parameter from 3.89 to 4.00 Å and the blocking of the β-hydride formation. Initial catalytic screening determines the synthetic route which yields the most active catalyst which subsequently undergoes thorough characterisation. The wealth of evidence generated confirms the interstitial location of lithium within the palladium lattice, as well as adding to the current understanding of the Pd-^interstitialB/C material. EELS analysis on Pd-^interstitialB is the closest to direct observation of boron within the palladium lattice to date. PDF on Pd-^interstitialLi shows 13.7 % of the palladium octahedral interstitial sites are occupied by lithium. This is the first report of interstitial lithium within palladium to date. The effect of the interstitial modification on catalytic hydrogenation by two elements that have opposite effects on the surface electronics of the host palladium gives intriguing results. The effect on catalysis varies depending on the conditions investigated. This bank of hydrogenation data allows an informed choice as to which interstitial material would be best suited to the gas or liquid phase catalytic hydrogenation under investigation.

Increased efficacy of light and laser applications in medicine is achieved by accurate light dosimetry. A minimally invasive technique for the determination of the optical coefficients of tissue involves interstitial measurements of the local fluence rate at two or more points in the tissue using isotropic, fibre optic detectors and application of a diffusion model of light propagation. The diffusion models assume simple, homogeneous tissue geometries, possibly oversimplifying the effect of tissue heterogeneities and boundaries. The primary goals of this study were to investigate the influence of realistic finite geometries on the fluence rate distribution and to quantify the systematic errors in the derived optical properties. A Monte Carlo model was developed to predict the fluence rate distribution in any plane of interest in a medium and was verified by comparison with diffusion theory solutions for simple geometries. Fluence rate measurements were made in optically infinite and semi-infinite phantoms for a wide range of optical properties and it was determined that the optical coefficients were derived accurately for phantoms with ueff> 0.2 mm-1 and 2 < ut'<10 mm-1. Measurements were also made in finite spherical volumes with absorbing (Rd = 0.35) and diffuse reflecting (Rd =0.85) boundaries for three optical phantoms and comparisons of the experimental fluence rates with the predictions of the finite volume Monte Carlo model are presented. Boundary effects were observed to be significant within 4 transport mean free paths (mfp') of the boundary. The optical coefficients were derived by applying a diffusion solution for an infinite medium and it was determined that within 2 mfp' of the boundary, the derived ua was overestimated by 40% and underestimated by 20% for the absorbing and reflecting boundaries, respectively. / Thesis / Master of Science (MS)

Master of Science / Department of Clinical Sciences / Daniel U. Thomson / Acute Interstitial Pneumonia (AIP) is a costly issue that affects feedlot cattle, especially during hot and dry summers. Research has yet to elucidate the exact etiology of AIP; therefore this study was conducted to determine possible factors that contribute to AIP in feedlot cattle. During the summer of 2011 in a 55,000 head feedyard in southwest Kansas, animals exhibiting clinical signs of AIP were selected for ante-mortem examination and data collection. The animal population within the feedlot consisted of 75% heifers and 25% steers. Approximately 50% of the animal population was black hided animals. Ante-mortem data consisted of rumen gas cap measurement for NH3 and H2S, rumen pH, serum chemistry, rectal temperature, and body weight. Post-mortem cases with and without ante-mortem evaluations were also selected for an additional examination. Postmortem examination included similar data as ante-mortem examination with addition of visual and histological examination of lung tissue. There were 31 ante-mortem cases of clinical AIP with the following observations (mean ± SD): rectal temperature 105.3 ± 0.7 °F, weight 1098 ± 123 lbs., H2S 136 ± 133.3 ppm, and rumen pH 6.4 ± 0.5. Twenty-five healthy cohorts were selected from identical pens to serve as controls. Observations from control animals were: rectal temperature 103.7 ± 1.1 °F, weight 1113 ± 133.3lbs, H2S 269.8 ± 311.6 ppm and rumen pH 6.2 ± 0.6. A total of 61 post-mortem cases with a preliminary diagnosis of AIP were analyzed and displayed the following values: H2S 1279.7 ± 1569 ppm, and rumen pH 6.3 ± 0.36. Fifty-three of these postmortem cases had diffuse, focal and /or patchy AIP confirmed by histology.

Sarcoidosis is a multisystem inflammatory disorder of unknown aetiology. The immune pathology is characterised by dysregulated T cell (T_H1) activity, macrophage activation and granuloma formation, resulting in systemic inflammation, and organ dysfunction. I hypothesised that, as the systemic precursor to the macrophage, altered monocyte activity in sarcoidosis may contribute to the early immune pathology of the disease. In this thesis, I examined their phenotype, four key monocytic functions: cytokine production, suppression of T cell proliferation, phagocytosis and fusion (as a precursor to granulomagenesis); and their gene expression profile compared to monocytes from healthy controls. My data show that the expanded monocyte compartment comprise a greater proportion of the inflammatory (CD14⁺⁺CD16⁺) and patrolling (CD14⁺CD16⁺⁺) subsets, increased TNFα and IL-12 and decreased IL-10 and IL-4 production in sarcoidosis compared with healthy controls. The IL-10 deficit renders the monocytes less able to regulate T cell proliferation or their own fusion to multinucleate giant cells, potentially contributing to T cell expansion and granuloma formation respectively. Additionally, sarcoidosis monocytes are less able to phagocytose inert material. I also showed that previously reported deficiency in invariant NKT cells and low serum vitamin D levels in sarcoidosis may be linked to reduced IL-10 production by monocytes. Vitamin D treatment in vitro restored most of these deficiencies and provides a potential therapeutic method for manipulating monocyte function and disease genesis in sarcoidosis.

As comunidades da fauna de copépodes de águas intersticiais da zona hiporrêica de um igarapé da Amazônia Central e de um rio da mata atlântica da região Sudeste do Brasil são comparadas quanto à composição, diversidade, e distribuição dos organismos. A relação das espécies identificadas com os fatores abióticos é analisada, com o objetivo de se estabelecer quais são os fatores determinantes para a distribuição das mesmas. Os fatores abióticos mensurados são: temperatura, pH, oxigênio dissolvido e granulometria do sedimento. Na areia grossa, há dominância de copepoditos e do gênero Forficatocaris (uma espécie para a mata atlântica e duas novas para a Amazônia). Essas três espécies e os copepoditos exploram o mesmo tipo de micro-hábitat no substrato. Quando a areia média é o substrato predominante, há o aumento na presença dos outros gêneros, como Potamocaris (uma espécie para a mata atlântica e uma nova espécie para a Amazônia) e Parastenocaris (mata atlântica), além do declínio no número de copepoditos. Há uma relação direta entre a temperatura e a distribuição dos microcrustáceos, ocorrendo o predomínio destes animais em temperaturas mais baixas. Há diferenças significativas dos valores de pH quando comparadas localidades distintas (Amazônia e mata atlântica); no entanto, quando comparadas as estações seca e chuvosa de um mesmo local, essa diferença não aparece. Sugere-se que o pH influencie na composição das espécies, e não em sua distribuição. Há um número similar de espécies ocupando os dois ambientes e um padrão de distribuição da fauna hiporrêica. Estas semelhanças apontam para a existência de padrões na estrutura e funcionamento destas comunidades naturais de microcrustáceos intersticiais, moldadas por pressões seletivas parecidas. / The assemblages of the copepod fauna from interstitial waters in the hyporheic zones from a stream in Central Amazon and a stream in the Atlantic rainforest of southeastern Brazil were compared in terms of composition, diversity and organism distribution. The relation of the identified species with abiotic factors was analyzed, aiming at establishing which factors were determinant for their distribution. The abiotic factors analyzed were: temperature, pH, dissolved oxygen, and sediment granulometry. In thick sand, there is predominance of copepodites and of the genus Forficatocaris (one species found in the Atlantic rainforest and two new species in the Amazon). These three species of Forficatocaris and the copepodites explore the same kind of microhabitat in the sediment. When medium size of sand grains prevail, there is an increase in the presence of other genera, such as Potamocaris (one species for the Atlantic rainforest and one new species for the Amazon) and Parastenocaris (Atlantic rainforest), besides a decline in number of copepodites. There is a direct ratio between the temperature and the distribution of microcrustaceans, with a predominance of these invertebrates in lower temperatures. There are significant differences in pH values when both localities (Amazon and Atlantic rainforest) are compared; however, comparisons between seasons (lower rainfall versus rainy periods) in a same location did not yield differences. It is suggested that the pH influences species composition, but not species distribution. There is a similar number of species inhabiting both environments and a distribution pattern for the hyporheic fauna. These similarities point at the existence of patterns in the structure and behavior in these natural communities of interstitial microcrustaceans, molded by similar selective pressures.

According to statistics from the American Heart Association, valvular heart disease directly leads to about 20,000 deaths a year and contributes to an additional 50,000. While significant advancements have been made in the treatment options available for valvular heart disease, complications still occur. For this reason, the future of valvular heart disease treatment lies in understanding the physiology of the heart valve, and subsequently bioengineering a valve from one's own tissue to mimic native valve processes. Valvular interstitial cells (VICs) are the major cell type populating the valve matrix. In the inactive fibroblast-like state, these cells are responsible for extracellular matrix deposition. Activated VICs display a myofibroblast morphology characterized by the expression of alpha smooth muscle actin and are responsible for valve maintenance and repair. The activation of VICs is hypothesized to be stimulated by mechanical tension, which, in the presence of TGF-â1 allows the complete differentiation of VICs from the inactive to the active form. However, little is known about the potential for reversal or dedifferentiation from the active to inactive state. The purpose of this study was to determine whether substrate stiffness, the mechanical tension hypothesized to initiate VIC activation, modulates alpha smooth muscle actin expression in the presence and absence of TGF-â1. To mimic conditions found in vivo, substrates were varied from physiologic to pathological stiffness levels. Results showed that when freshly isolated VICs are cultured in the presence of serum, alpha smooth muscle actin expression increased on all substrate stiffnesses. In TGF-â-free medium, there was an apparent increase on all stiffness levels as well, but a statistical significance between groups could not be demonstrated. Immunoblots used to detect TGF-â1 showed that intracellular TGF-â1 was upregulated in VICs cultured in the presence of serum compared to those cultured in TGF-â-free medium. Taken together, these results suggest that freshly isolated VICs become activated, as indicated by increased expression of alpha smooth muscle actin, on all substrate levels in the presence of serum. It also appears as though unknown factors which are present in serum are required to stimulate significant autocrine production of TGF-â1. To determine whether VICs which had transitioned to the myofibroblast phenotype had the ability to dedifferentiate, cells were cultured on polystyrene for a minimum of four days then replated on substrates of varying stiffness. Analysis of alpha smooth muscle actin expression showed that, in the presence of serum and when replated on all of substrates used, alpha smooth muscle actin expression decreased, suggesting that these cells indeed have the potential to dedifferentiate. A change in cell morphology to a more rounded phenotype as well as the loss of visible stress fibers further supported this possibility. These studies represent a unique approach to studying phenotypic differentiation of valvular interstitial cells. Using acrylamide substrates of varying stiffness, and growth factor free media, we have shown that by altering substrate stiffness, changes in alpha smooth muscle actin expression consistent with differentiation and dedifferentiation can be induced. This potential for dedifferentiation suggests that in engineering the next generation of bioartificial valves, it may be possible to use the patient's own cells to seed the manufactured scaffold. This would avoid complications associated with current treatments, including immune rejections.

Introdução: a cistite intersticial é doença crônica do trato urinário inferior cujos sintomas são: aumento da freqüência urinária, nictúria, dor pélvica ou perineal que piora com a repleção vesical e melhora com a micção. A etiopatogenia não é totalmente conhecida, mas há indícios de que os glicosaminoglicanos e proteoglicanos que revestem o urotélio vesical possam participar da sua gênese. A perda destes componentes protetores facilitaria o contato de íons e solutos presentes na urina com as porções mais profundas do urotélio desencadeando e perpetuando um processo inflamatório local. Para tentar entender seu metabolismo, investigamos o comportamento dos glicosaminoglicanos na urina e no tecido (biópsia do urotélio vesical) de pacientes portadoras de cistite intersticial e de incontinência urinária de esforço genuína. Casuística e métodos: o perfil e expressão gênica de glicosaminoglicanos no tecido, e o perfil dos glicosaminoglicanos da urina de 11 pacientes com cistite intersticial foram comparados aos de 11 pacientes com incontinência urinária de esforço. A análise estatística foi feita através de teste T e Anova, considerando significativos valores p<0,05. Resultados: verificamos que pacientes com cistite intersticial excretam menor concentração de glicosaminoglicanos na urina do que as portadoras de incontinência urinária de esforço (0,45 ± 0,11 x 0,62 ± 0,13 g/mg creatinina, p<0,05), porém sem redução do conteúdo de glicosaminoglicanos no urotélio. Na imunofluorescência o urotélio de pacientes com cistite intersticial mostrou maior marcação de TGF-beta, decorim (um proteoglicano de condroitim/dermatam sulfato), fibronectina e de ácido hialurônico. Foi identificada menor expressão gênica (PCR em tempo real) das sintases e uma hialuronidase do ácido hialurônico no urotélio das cistites intersticiais. Conclusão: a combinação desses resultados sugere que os glicosaminoglicanos podem estar relacionados ao processo contínuo de inflamação e remodelamento do urotélio disfuncional presente na cistite intersticial. O estudo da expressão gênica pode representar uma altenativa para o entendimento da doença. / Introduction: interstitial cystitis is a chronic disease of the lower urinary tract whose symptoms are: increased urinary frequency, nocturia, perineal or pelvic pain that worses with bladder filling and improves with urination. The pathogenesis is not fully known, but there is evidence that proteoglycans and glycosaminoglycans lining the bladder urothelium can participate in its genesis. The loss of these protective compounds facilitate the contact of ions and solutes in the urine with deeper portions of bladder wall triggering and perpetuating a local inflammatory process. We investigated GAG behavior in urine and tissue (biopsy of bladder urothelium) of patients with IC/PBS and genuine stress urinary incontinence (SUI) in an attempt to better understand its metabolism. Patients and Methods: gene expression and glycosaminoglycans profile in tissue, and glycosaminoglycans profile in urine of 11 patients with interstitial cystitis were compared to 11 patients with pure urinary stress incontinence. Statistical analysis were performed using t Student test and Anova, considering significant when p<0,05. Results: patients with interstitial cystitis excreted lower concentration of glycosaminoglycans in urine when compared to those with pure urinary stress incontinence (respectively 0.45 + 0.11 x 0.62 + 0.13 mg/mg creatinine, p< 0.05). However, there was no reduction of the content of glycosaminoglycans in the urothelium of both patients. The immunofluorescence study showed that patients with interstitial cystitis had a stronger staining of TGF-beta, decorin (a proteoglycan of chondroitin/dermatan sulfate), fibronectin and hyaluronic acid. We were able to indentify by real-time PCR lower gene expression of hyaluronic acid synthases and hyaluronidase in the urothelium of patients with interstitial cystitis. Conclusion: the results suggest that glycosaminoglycans may be related to the ongoing process of inflammation and remodeling of the dysfunctional urothelium that is present in the interstitial cystitis. The study of the gene expression may represent an alternative to understand the disease

Orientador: Carlos Roberto Grandini / Banca: Alfredo Gonçalves Cunha / Banca: Paulo Noronha Lisboa Filho / O Programa de Pós-Graduação em Ciência e Tecnologia de Materiais, PosMat, tem caráter institucional e integra as atividades de pesquisa em materiais de diversos campi da Unesp / Resumo: Desde a descoberta dos supercondutores com alta Tc, vários trabalhos têm sido efetuados sobre as diferentes propriedades destes materiais. As cerâmicas Y'BA IND.2' "C IND.U 'IND.3' 'O IND. 7-'delta' mostraram que tem suas propriedades supercondutoras fortemente afetadas pela quantidade de oxigênio. Mais recentemente, medidas de relaxações anelásticas em 'LA IND.2'CU 'O IND. 4+'delta' mostraram que a remoção deste elemento pode ser relacionada com dois eventos. Um deles é o decréscimo na mobilidade entre dois planos adjacentes CuO e o outro, é o aumento no número de padrões de mobilidade para os octaedros CU 'O IND. 6'. Para SM'BA IND.2' "C IND.U 'IND.3' 'O IND. 7-'delta' (SBCO), a possibilidade de uma estequiometria de oxigênio variável e sua alta mobilidade nos planos... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Since the discovery of the high Tc superconductors, several works have been made about the different propoerties of these materials. Y'BA IND.2' "C IND.U 'IND.3' 'O IND. 7-'delta' ceramic showed to have its superconducting properties strongly affected by the oxygen content. More recently, anelastic relaxation measurements in 'LA IND.2'CU 'O IND. 4+'delta', showed that the remotion of this element can be related to two events. One is the decrease in mobility between two adjacent CuO planes, and the other is the increase in the number of tilting patterns of the Cu 'O IND. 6' octahedra. For SM'BA IND.2' "C IND.U 'IND.3' 'O IND. 7-'delta' (SBCO), the possibility of variable stoichiometry and the high mobility of oxygen in the... (Complete abstract, click electronic access below) / Mestre

Interstitial cystitis (IC)/painful bladder syndrome (PBS) is a functional visceral disorder characterized by increased bladder activity and chronic pelvic pain in the absence of a pathobiological condition. Enhanced sensory transduction of peripheral bladder afferents is hypothesized to contribute to the pain and mechanical hypersensitivity of IC/PBS patients. The aim of this thesis is to test the hypothesis that purinergic receptors, including ionotropic P2X and metabotropic P2Y, are important for sensory transmission in bladder afferent neurons and may be involved in bladder hypersensitivity after bladder tissue insults. Electrophysiological, single cell RT-PCR and immunohistochemistry techniques were performed in bladder afferent neurons from naïve and bladder inflamed mice to test the hypothesis. In Chapter 2, I characterized the distribution and function of P2X receptors in thoracolumbar (TL) and lumbosacral (LS) dorsal root ganglia (DRG) neurons innervating the urinary bladder, and found that LS and TL bladder neurons have differential purinergic signaling and distinct membrane electrical properties. In Chapter 3, I examined the sensitization of bladder afferent neurons and the plasticity of P2X receptor function in a mouse model of chemical induced bladder inflammation. P2X-mediated signals in LS and TL bladder neurons after bladder inflammation were enhanced compared with those in saline-treated controls, suggesting the importance of P2X in bladder hypersensitivity associated with cystitis. In Chapter 4, the modulation of P2Y on P2X function and the co-localization of P2Y and P2X were examined in bladder sensory neurons. It has been found that P2Y2 receptor enhances bladder sensory neuron excitability and facilitates the response of homomeric P2X2 receptor to the purinergic agonist (ATP). The present study provides evidence that LS and TL mouse bladder sensory neurons exhibit distinct P2X signaling, and the function of P2X receptors could be facilitated during bladder inflammation and modulated by activation of P2Y2 receptor, indicating an involvement of P2X and P2Y2 receptors as mechano- and chemosensors in bladder sensory transmission under normal conditions and in bladder hypersensitivity associated with inflammation.