Coal has been an important natural resource of energy in the Illinois Basin for generations. In addition to the organic macerals in coal, there is inorganic matter containing minerals and trace elements. With growing demand for economic and critical metals including Rare Earth Elements and Yttrium (REY), coals containing anomalously high concentrations of trace elements, as well as their associated coal mine wastes, and drainages have been explored as promising secondary resources, but there were no former studies of REY in Illinois basin CMD. CMD samples were collected from 35 abandoned coal mine sites from three regions of the Illinois basin. Region 1 (R1) the southern extent of the basin extending west along the cottage grove fault system and includes Hicks dome, a nexus of regional hydrothermal activity and provenance of the Illinois Kentucky Fluorite District (IKFD) ore deposits; Region 2 (R2) comprised locations situated in western Illinois along the Du Quoin Monocline; and Region 3 (R3) comprised locations situated in northern Illinois, farthest from the Hicks Dome. Two hypotheses were tested in this study: (1) that pH and ΣREY would share an inverse correlation, with the greatest abundances of REY found in the most acidic drainages; and (2) hydrothermal activity associated with Hicks Dome in southern Illinois was the source of REY enrichment in the coals, and so, REY abundance and pattern would reflect proximity to the cryptoexplosive complex, with the greatest enrichments expected in R1, closest to Hicks Dome. The geochemical data of 42 CMD samples was examined was analyzed to test these two ii hypotheses. Samples ranged from extremely acidic (pH=1.93) to circumneutral (pH=7.6) with an average pH value of 3.4. Total REY values (ΣREY) averaged 1,057 μg/L across all samples and ranged from 0.4-9,879 μg/L while Σcritical-REY abundances (Nd, Eu, Tb, Dy, and Y) averaged 611 μg/L and ranged from 0.2-7,213 μg/L. Furthermore, there are significant direct correlations of ΣREY with Al, Si, SO4, Zn, Ni, Cu, Cd, Co and no correlations with Fe, Ca, P, Ba, and V. In the course of investigation, it was found that pH and linear concentration values for REY correlate poorly. However, logarithmic values of REY concentrations (i.e., log[ΣREY]), as well as the above trace metals have strong inverse correlations with pH( (r=- 0.84, p

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第19404号 / 医博第4055号 / 新制||医||1012(附属図書館) / 32429 / 京都大学大学院医学研究科医学専攻 / (主査)教授 野田 亮, 教授 瀬原 淳子, 教授 藤渕 航 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Bakgrund: Sjukdomen åldersrelaterad makuladegeneration (AMD) är en är av de vanligaste anledningarna till grav synnedsättning i västvärlden. Sjukdomen medför att den centrala synen försämras för patienten. Det finns en torr och en våt form. Med den våta formen sker synförsämringen i ett snabbare förlopp men kan behandlas med läkemedel som injiceras i ögats glaskropp. Synförsämringen skapar olika problem för patienten att hantera i deras vardagsliv. I relation till vardagliga aktiviteter så som socialt och fysiskt finns den närvarande. Syfte: Att beskriva patientens uppfattningar av att leva med sjukdomen våt AMD. Metod: En kvalitativ design har använts med en fenomenografisk forskningsansats. Patienter från en ögonmottagning i Mellansverige har enskilt intervjuats. Data har sedan analyserats enligt en fenomenografisk analys. Resultat: Fyra stycken beskrivningskategorier identifierades som handlade om patienternas uppfattningar av sin sjukdom. Medvetenhet om sjukdomen, förlust av självständighet, att kunna anpassa sig och att känna tillit till sjukvården. Slutsats: Att leva med sjukdomen våt AMD medför förändringar i patientens vardagsliv och påverkar det på olika sätt. För att kunna förstå patientens uppfattningar med att leva med sjukdomen är det viktigt att belysa och lyfta fram dessa för att kunna hitta metoder för att uppmärksamma denna patientgrupps behov av stöd och hjälp vid besöken på ögonkliniken.

Eine retrospektive Studie über das Progressionsrisiko asymptomatischer früher Altersabhängiger Makuladegeneration in die symptomatische Spätphase überzugehen. Anhand von Lipofuszin-Mustern, die per Fundusautofluoreszenzmessung erkannt werden können, lassen sich Risikopatienten identifizieren. Diese Methode könnte zukünftig im klinischen Alltag als nicht-invasive, kostengünstige Screening-Methode zur Anwendung kommen, um Risikopatienten einer intensivierten Therapie unterziehen zu können, bevor sie eine Beeinträchtigung ihrer Sehkraft erfahren.

Dissimilatory sulphate reduction, brought about by the action of sulphate reducing bacteria (SRB) was used in the treatment of acid mine drainage (AMD) in a fluidised bed bioreactor. Biologically produced hydrogen sulphide and bicarbonate ions, by SRB, facilitated the precipitation of heavy metals and the generation of alkalinity in the synthetic acid mine water, respectively. The SRB that had been selected were able to utilize acetate as the sole carbon source and were capable of growing in the bioreactors at low pHs, facilitating an increase in the influent pH from 2.75-7.0 to 5.4-7.8, after a 24-hour hydraulic retention time (HRT). The precipitation efficiencies for Fe, Mn, Zn, Cu, Cr and Al after a HRT of 24 h as metal sulphides ranged between 84- 99% for influent pH values of between 4 and 7, and above 54% for influent pH values between 2.75 and 4. Microbial metabolic activity decreased with decreasing influent pH. This was inferred from the decreasing differences in chemical oxygen demand (COD) depletion rate over a 24 h HRT, as influent acidity levels approached pH 2.75. Molecular studies, using PCR-DGGE analysis on the microbial consortium in the bioreactor, revealed the presence of at least 8 different bacterial species in the consortium. Attempts at sequencing these bands yielded inconclusive results, with the bands showing sequence homology to a large number of previously uncultured and undescribed bacteria. Scanning electron microscopy confirmed the presence of bacteria of different morphology, as well as the presence of biofilms, which account for the heavy metal and low pH tolerances that the bacteria sustained.

Objetivos: Avaliar o potencial terapêutico e a segurança do uso intravítreo de (FMMO) contendo células CD34+ em pacientes portadores de degeneração macular relacionada com a idade na forma atrófica. Casuística e Métodos: Foram avaliados 10 pacientes com degeneração macular relacionada à idade (DMRI) seca e acuidade visual no pior olho <=20/100. Foi obtido aspirado da medula óssea de todos os pacientes, e após o processamento do material no hemocentro, foi injetado 0,1 ml da suspensão de FMMO intravítreo no olho com pior acuidade. Os pacientes foram avaliados no baseline, 1, 3, 6, 9 e 12 meses após a injeção. Todos realizaram medida da melhor acuidade visual corrigida (MAVC), microperimetria, eletrorretinografia multifocal (ERGmf), autofluorescência, Tomografia de coerência óptica (OCT) e responderam o questionário VFQ-25 em todos seguimentos. Também foi realizada angiografia fluoresceínica antes da injeção, seis e doze meses após. Resultados: Todos os pacientes completaram o seguimento de seis meses, e seis finalizaram os doze meses. Antes da injeção, a média da MAVC foi de 1,18 logMAR (20/320-1); variando de 20/125 a 20/640-2. Aos doze meses, a média foi de 1,0 logMAR (20/200), com melhora significativa em todos os meses de seguimento. A média do limiar de sensibilidade na microperimetria mostrou melhora significativa a partir do sexto mês (p=0,009). Ao se dividirem os pacientes com área de atrofia maior e menor, por meio da medida da hipoautofluorescência, observou-se que a melhora foi significativa apenas no grupo de menor atrofia. Não houve diferença significativa na ERGmf. A angiofluoresceinografia não apresentou crescimento de neovasos ou tumores. O questionário de qualidade de vida mostrou diferença significativa na saúde mental (p=0,003) e na visão de cores (p=0,005) e forte tendência à significância na análise que abordou a visão geral (p=0,05) e dependência (p=0,067). Houve declínio em relação à saúde geral (p=0,77). Conclusões: Os resultados indicam que o uso de FMMO intravítreo em pacientes com DMRI é seguro e está associado à melhora da acuidade visual e microperimetria. Pacientes com área menor de atrofia têm melhor resposta. Não é possível afirmar, mas acredita-se no resgate funcional das células em sofrimento, que ainda não se degeneraram. / Objectives: To assess the therapeutic potential and safety of the intraviteral use of a bone marrow mononuclear fraction (BMMF) containing CD 34+ cells in patients with the atrophic form of age-related macular degeneration (AMD). Casuistic and Methods: The study was conducted on 10 patients with the atrophic form of ARMD with worse eye visual acuity <=20/100. Bone marrow was aspirated from each patient under local anesthesia. After processing and separation of mononuclear cells, 0.1 ml of the suspension was injected intravitreally into the eye of lower acuity. The patients were evaluated at baseline and 1, 3, 6, 9 and 12 months after the injection. All were submitted to measurement of best corrected visual acuity (BCVA), microperimetry, multifocal electroretinography (ERGmf), autofluorescence, and optical coherence tomography (OCT) and all responded to the VFQ-25 questionnaire at all follow-up visits. Fluorescein angiography was performed before the injection and six and 12 months later. Results: All patients completed the six month follow-up and six completed the 12 month follow-up after the injection. Before the injection, mean BCVA was 1.18 logMAR (20/320-1), ranging from 20/125 to 20/640-2 and at 12 months it was 1.0 logMAR (20/200), with a significant improvement over all followup months. Mean perimetric threshold sensitivity improved significantly starting at the sixth month (p=0.009). When the patients with a larger area of atrophy measured by hypoautofluorescence were considered separately, a significant improvement was observed only in the group with lower atrophy. There was no significant difference in electroretinography. Angiofluoresceinography did not reveal neovessel or tumor growth. The quality of life questionnaire showed a significant difference in mental health (p=0.003) and color vision (p=0.005), and a strong tendency in the analysis of general vision (p=0.05) and dependence (p=0.067). There was a decline in general health (p=0.77). Conclusions: The results indicate that the use of intravitreal BMMF in patients with AMD is safe and is associated with improved visual acuity and microperimetry. Patients with a smaller atrophy area obtained a better response. The paracrine effect of these cells may explain the functional improvement observed in the present study; however, a larger series should be study to confirm these clinical findings.

Objetivos: Avaliar o potencial terapêutico e a segurança do uso intravítreo de (FMMO) contendo células CD34+ em pacientes portadores de degeneração macular relacionada com a idade na forma atrófica. Casuística e Métodos: Foram avaliados 10 pacientes com degeneração macular relacionada à idade (DMRI) seca e acuidade visual no pior olho <=20/100. Foi obtido aspirado da medula óssea de todos os pacientes, e após o processamento do material no hemocentro, foi injetado 0,1 ml da suspensão de FMMO intravítreo no olho com pior acuidade. Os pacientes foram avaliados no baseline, 1, 3, 6, 9 e 12 meses após a injeção. Todos realizaram medida da melhor acuidade visual corrigida (MAVC), microperimetria, eletrorretinografia multifocal (ERGmf), autofluorescência, Tomografia de coerência óptica (OCT) e responderam o questionário VFQ-25 em todos seguimentos. Também foi realizada angiografia fluoresceínica antes da injeção, seis e doze meses após. Resultados: Todos os pacientes completaram o seguimento de seis meses, e seis finalizaram os doze meses. Antes da injeção, a média da MAVC foi de 1,18 logMAR (20/320-1); variando de 20/125 a 20/640-2. Aos doze meses, a média foi de 1,0 logMAR (20/200), com melhora significativa em todos os meses de seguimento. A média do limiar de sensibilidade na microperimetria mostrou melhora significativa a partir do sexto mês (p=0,009). Ao se dividirem os pacientes com área de atrofia maior e menor, por meio da medida da hipoautofluorescência, observou-se que a melhora foi significativa apenas no grupo de menor atrofia. Não houve diferença significativa na ERGmf. A angiofluoresceinografia não apresentou crescimento de neovasos ou tumores. O questionário de qualidade de vida mostrou diferença significativa na saúde mental (p=0,003) e na visão de cores (p=0,005) e forte tendência à significância na análise que abordou a visão geral (p=0,05) e dependência (p=0,067). Houve declínio em relação à saúde geral (p=0,77). Conclusões: Os resultados indicam que o uso de FMMO intravítreo em pacientes com DMRI é seguro e está associado à melhora da acuidade visual e microperimetria. Pacientes com área menor de atrofia têm melhor resposta. Não é possível afirmar, mas acredita-se no resgate funcional das células em sofrimento, que ainda não se degeneraram. / Objectives: To assess the therapeutic potential and safety of the intraviteral use of a bone marrow mononuclear fraction (BMMF) containing CD 34+ cells in patients with the atrophic form of age-related macular degeneration (AMD). Casuistic and Methods: The study was conducted on 10 patients with the atrophic form of ARMD with worse eye visual acuity <=20/100. Bone marrow was aspirated from each patient under local anesthesia. After processing and separation of mononuclear cells, 0.1 ml of the suspension was injected intravitreally into the eye of lower acuity. The patients were evaluated at baseline and 1, 3, 6, 9 and 12 months after the injection. All were submitted to measurement of best corrected visual acuity (BCVA), microperimetry, multifocal electroretinography (ERGmf), autofluorescence, and optical coherence tomography (OCT) and all responded to the VFQ-25 questionnaire at all follow-up visits. Fluorescein angiography was performed before the injection and six and 12 months later. Results: All patients completed the six month follow-up and six completed the 12 month follow-up after the injection. Before the injection, mean BCVA was 1.18 logMAR (20/320-1), ranging from 20/125 to 20/640-2 and at 12 months it was 1.0 logMAR (20/200), with a significant improvement over all followup months. Mean perimetric threshold sensitivity improved significantly starting at the sixth month (p=0.009). When the patients with a larger area of atrophy measured by hypoautofluorescence were considered separately, a significant improvement was observed only in the group with lower atrophy. There was no significant difference in electroretinography. Angiofluoresceinography did not reveal neovessel or tumor growth. The quality of life questionnaire showed a significant difference in mental health (p=0.003) and color vision (p=0.005), and a strong tendency in the analysis of general vision (p=0.05) and dependence (p=0.067). There was a decline in general health (p=0.77). Conclusions: The results indicate that the use of intravitreal BMMF in patients with AMD is safe and is associated with improved visual acuity and microperimetry. Patients with a smaller atrophy area obtained a better response. The paracrine effect of these cells may explain the functional improvement observed in the present study; however, a larger series should be study to confirm these clinical findings.

Wet age related macular degeneration (wet AMD) is a highly debilitating retinal disease, the third leading cause of blindness in the world and one the most expensive ocular conditions to care for. Wet AMD is characterised by the proliferation of neovasculature through the retinal posterior and theorised to be, at least in part, induced and driven by excess vascular endothelial growth factor (VEGF). Many current treatments for wet AMD utilise anti-VEGF macromolecules that bind to VEGF. The retina, however, remains a largely inaccessible, and delicate, anatomical region. Due to difficulties in collecting clinical and experimental data, mathematical modelling is playing an increasingly prominent role in understanding the distribution (Pharmacokinetics, PK) and drug-to-target interactions (Pharmacodynamics, PD) for treatments of wet AMD. This thesis will focus on ordinary/partial differential equation (ODE/PDE) models for the PK/PD of anti-VEGF therapeutics, administered via intravitreal (IVT) injection into the mammalian eye. We start in Chapter 2 with a 2-compartment PK/PD ODE model of drug-VEGF interactions in the eye, analysing a clinical dataset to estimate key binding parameters between VEGF and the typical anti-VEGF molecule, ranibizumab. In Chapter 3, we extend the PK ODE framework of the 2-compartment model to include a mechanistic description of the retina, to estimate retinal permeability to macromolecules used for treating wet AMD. In Chapter 4, using the retinal PK model, we reintroduce VEGF to predict concentrations of free VEGF in the retina post-IVT injection. Chapters 5 and 6 model a hypothetical class of anti-VEGF molecules designed to bind not only VEGF but also existing vitreal superstructures, analysing how dose and binding kinetics impact ocular retention. Alongside these models we present analogous PDE models, addressing whether the assumption that concentrations are homogeneous across anatomical regions, as implicit in ODE models, is appropriate for macromolecular PK/PD in the mammalian eye.

Age-related macular degeneration (AMD) is a leading cause of visual impairment and blindness, affecting over 30 million people worldwide. It is characterized by the appearance of insoluble deposits known as drusen in the outer retina, between the retinal pigment epithelium (RPE) and Bruch's membrane. Drusen are heterogeneously composed of many compounds, including cholesterol, amyloid-β, and complement proteins. AMD also involves the accumulation of pigments collectively termed lipofuscin in RPE lysosomes. The underlying causes of AMD are unknown, but studies have implicated inflammatory processes in its pathogenesis.

No description available.