The magnetic cleanliness of a spacecraft during magnetic measurements is an important aspect in the design of many space science missions. The adequate reduction or removal of the spacecraft's magnetic disturbance plays a vital role in allowing the ambient magnetic field to be measured with the required accuracy. There are three main approaches to reduce the impact of the spacecraft's magnetic disturbance on the final magnetic measurement, with each approach imposing its own set of changes and constraints on the spacecraft. In turn these changes and constraints introduce additional complexity and cost to the system design. The required changes in the spacecraft's mission profile and configuration also need to be factored in during the design phase of a spacecraft, but cannot be avoided if high quality measurements are desired.  One of these approaches is the use of a magnetic cleanliness programme, and such programmes have a long history of successful use on large satellite missions.CubeSats have become increasingly technically capable and have in recent years begun to undertake scientific missions with challenging sensitivity requirements, including for magnetic measurements. The small size of the CubeSat form factor poses some unique challenges to the implementation of magnetic cleanliness techniques, but are also in increased need of limiting the residual magnetic moment when compared to large satellites. This thesis details the early phases of the magnetic cleanliness programme on the FORESAIL-2 science mission. Nine magnetic cleanliness requirements on the FORESAIL-2 satellite platform were derived from the FORESAIL-2 measurement and instrument requirements. A simple magnetic model was established, the results of which were used to propose a configuration of spacecraft subsystems. The resulting preliminary configuration of subsystems reduced the effective magnetic field of the REPE payload at the sensor by 352pT, 30.1%, when compared to the worst-performing configuration. Subsequently an improved model, utilising RSS analysis, was created. Combined with updated location information for each subsystem, defined using the proposed configuration, this second model yielded an estimated magnetic field of 2710pT at the reference point. The results of the second model were also used to identify the CDE payload and the TT&C subsystem as potentially problematic from a magnetic cleanliness perspective. A list of ferromagnetic materials was compiled, and a total mass of 453.72g of ferromagnetic materials was estimated. The work presented in this thesis is expected to form the basis of FORESAIL-2's continued magnetic cleanliness programme throughout the design and integration phases of the project.  For example, the improved model could be extended to include the estimated magnetic dipole moment's of each subsystem. Additionally, the inventories of materials, currents, and frequencies established as part of this thesis can be maintained throughout the FORESAIL-2's development cycle, and used to update the estimated total magnetic field of the spacecraft platform.

京都大学 / 0048 / 新制・課程博士 / 博士(理学) / 甲第17972号 / 理博第3916号 / 新制||理||1565(附属図書館) / 80816 / 京都大学大学院理学研究科物理学・宇宙物理学専攻 / (主査)教授 高橋 義朗, 教授 田中 耕一郎, 教授 石田 憲二 / 学位規則第4条第1項該当 / Doctor of Science / Kyoto University / DGAM

No / Incorporating edge activators (surfactants) into liposomes was shown previously to improve estradiol vesicular skin delivery; this phenomenon was concentration dependent with low or high concentrations being less effective. Replacing surfactants with limonene produced similar behaviour, but oleic acid effects were linear with concentration up to 16% (w/w), beyond which it was incompatible with the phospholipid. This present study thus employed high sensitivity differential scanning calorimetry to probe interactions of additives with dipalmitoylphosphatidylcholine (DPPC) membranes to explain such results. Cholesterol was included as an example of a membrane stabiliser that removed the DPPC pre-transition and produced vesicles with a higher transition temperature (Tm). Surfactants also removed the lipid pre-transition but reduced Tm and co-operativity of the main peak. At higher concentrations, surfactants also formed new species, possibly mixed micelles with a lower Tm. The formation of mixed micelles may explain reduced skin delivery from liposomes containing high concentrations of surfactants. Limonene did not remove the pre-transition but reduced Tm and co-operativity of the main peak, apparently forming new species at high concentrations, again correlating with vesicular delivery of estradiol. Oleic acid obliterated the pre-transition. The Tm and the co-operativity of the main peak were reduced with oleic acid concentrations up to 33.2 mol%, above which there was no further change. At higher concentrations, phase separation was evident, confirming previous skin transport findings.

A eficácia de métodos convencionais de transmissão, utilizados para medir absorção de materiais altamente transparentes, é geralmente limitada pela reflexão e espalhamento de luz. A espectroscopia de Lente Térmica, por outro lado, não é sensível a esses fenômenos, e tem sido amplamente usada na determinação de baixas absorções ópticas. Neste trabalho, estudamos uma configuração de Lente Térmica de duplo feixe (onda contínua cw), desenvolvida recentemente, e suas aplicações. Essa configuração otimiza a técnica de Lente Térmica, e aumenta significativamente a sensibilidade de medida. Foram realizados alguns cálculos computacionais e testes experimentais dessa configuração, e os resultados foram comparados com os de outra configuração, tradicionalmente utilizada, denominada de feixe duplo no modo-descasado. Várias aplicações foram feitas para líquidos e sólidos. Como resultado, obtivemos o espectro de absorção da água pura entre 350 e 528 nm, que indicou um valor mínimo de aproximadamente 1,5 &#8226 10-5 cm-1 em torno de 380 nm, que é mais baixo do que todos os valores da literatura. Coeficientes tão baixos quanto 2 &#8226 10-7 cm-1 podem ser medidos para a água, com 1W de potência, utilizando essa configuração otimizada. Estimamos um limite de detecção de ~ 6 &#8226 10-9 cm-1 (P = 1 W) para o solvente CCl4, que corresponde (até onde sabemos) ao menor valor já encontrado na literatura para líquidos, utilizando-se laser cw. Quanto à detecção de traços de impurezas, o limite para o Cr (III) em solução aquosa foi de ~ 40 ppb (ng/mL) em 514 nm, que corresponde a aproximadamente metade da concentração máxima ideal de Cr (III) em águas potáveis e naturais. Foram obtidos alguns resultados preliminares para a variação do caminho óptico com a temperatura (ds/dT), em sólidos com diferentes geometrias. Para a sílica fundida (quartzo vítreo) Suprasil, determinamos um limite superior para o coeficiente de absorção, cujos valores, 1 &#8226 10-6 cm-1 (em 493 nm) e 1 &#8226 10-5 cm-1 (em 355 nm), também são menores do que os resultados da literatura nessa região do espectro. A alta sensibilidade da técnica permitiu obter a absorção, em 1064 nm, das matrizes de materiais laser dopados com Nd3+, sendo (1,8 &#177 0,1) &#8226 10-3 cm-1 para o vidro Q-98 (Kigre), e (5 &#177 1 &#8226 10-4 cm-1 para o cristal Nd:YAG. Realizamos também medidas de eficiência quântica de fluorescência em nanocristais semicondutores (CdSe/ZnS) suspensos em THF e tolueno, com resultado aproximadamente 5 vezes mais preciso do que o obtido por técnica convencional de fluorescência. As principais vantagens da configuração otimizada, em relação à tradicional, são: um procedimento experimental simples, boa precisão nas medidas de difusividade térmica e, principalmente, a alta sensibilidade da técnica. As desvantagens são: um tempo de medida mais longo, e a necessidade de amostras maiores. / The efficiency of conventional transmission methods used to measure absorption of hightransparent materials is usually limited by light scattering and reflection. On the other hand, Thermal Lens spectroscopy is insensible to such phenomena and has been widely applied to determinate low optical absorptions. In this thesis, we have studied a recently developed dualbeam (continuous wave - cw) Thermal Lens configuration as well as its practical applications. This configuration optimizes the technique and significantly improves the measurement sensitivity. Some computational calculations and experimental tests of this approach were carried out. The results were compared with those obtained using a traditional configuration, named Mode-mismatched Dual-beam Thermal Lens. Several applications were made for liquids and solids. As a result, we obtained the absorption spectrum for pure water in the range of 350 to 528 nm, which indicated a minimal value of approximately 1,5 &#8226 10-5 cm-1 around 380 nm, that is lower than those found in literature. Absorption coefficients as small as 2 &#8226 10-7 cm-1, can be measured for water, using 1W of excitation power, with this optimized configuration. We have estimated a detection limit of ~ 6 &#8226 10-9 cm-1 (P = 1 W) for CCl4 solvent, which corresponds (to the best of our knowledge) to the smallest value found in the literature for liquids using cw laser. With regard to the chemical trace analysis, the detection limit was ~ 40 ppb (ng/mL) at 514 nm for Cr (III) in aqueous solutions, which is nearly half of the maximum desired Cr (III) concentration in drinking and natural waters. Some preliminary results for the temperature coefficient of the optical path length (ds/dT) were obtained at solids with different geometries. For the fused-silica (vitreous quartz) Suprasil, we have determined an upper limit for the absorption coefficient, whose values, 1 &#8226 10-6 cm-1 at 493 nm, and 1 &#8226 10-5 cm-1 at 355 nm, also are lower than the values found in literature in this spectrum region. The high sensitivity of the technique allowed us to measure the absorption (at 1064 nm) of matrices of Nd3+ doped laser materials: (1,8 &#177 0,1) &#8226 10-3 cm-1 for Q-98 glass (Kigre), and (5 &#177 1) &#8226 10-4 cm-1 for Nd:YAG crystal. We carried out as well measurements of fluorescence quantum yield of semiconductor nanocrystals (CdSe/ZnS) suspended in THF and toluene solvents, whose result was approximately 5 times more accurate than that obtained with the conventional fluorescence technique. The main advantages of the optimized configuration are: a simple experimental procedure, a good accuracy for thermal diffusivity measurements, and most important the high sensitivity of the technique. The drawbacks are: a longer time of measurements, and the requirement of larger samples.

Myocardial infarction is a leading cause of morbidity and mortality worldwide. The purpose of this thesis was to develop strategies for the assessment of patients with suspected myocardial infarction using a high-sensitivity cardiac troponin I assay, and to evaluate the relationship between the aetiology of myocardial infarction and long term clinical outcomes to identify opportunities to modify outcomes. In the United Kingdom, approximately 1 million patients present to hospital with chest pain each year and are assessed for suspected myocardial infarction, yet fewer than 20% of patients receive this diagnosis. Prior clinical standards mandated the admission of patients for serial cardiac troponin testing to identify myocardial necrosis and determine if myocardial infarction had occurred. However, new high-sensitivity assays offer a magnitude improvement in diagnostic precision, and as such provide a novel approach to diagnose or exclude myocardial infarction at an earlier stage. In our first study, I evaluate the performance of a high-sensitivity cardiac troponin I assay as a risk stratification tool in patients with suspected acute coronary syndrome. A systematic review and individual patient-level data meta-analysis was performed, including prospective studies measuring high-sensitivity cardiac troponin I in patients with suspected acute coronary syndrome, where the diagnosis was adjudicated according to the universal definition of myocardial infarction. The primary outcome was myocardial infarction or cardiac death during the index hospitalization or at 30 days. Meta-estimates for primary and secondary outcomes were derived using a binomial-normal random effects model. Performance was evaluated in subgroups and across a range of troponin concentrations (2-16 ng/L) using individual patient data. A total of 22,457 patients were included in the meta-analysis (age 62 [15.5] years; n=9,329 (41.5%) women), of whom 2,786 (12.4%) experienced myocardial infarction or cardiac death at 30 days. Cardiac troponin I concentrations were < 5 ng/L at presentation in 11,012 (49%) patients, with a negative predictive value of 99.5% (95% confidence interval [CI] 99.3-99.6) for myocardial infarction or cardiac death at 30 days. Lower thresholds did not improve safety, but did significantly reduce the proportion identified as low risk. This threshold of 5 ng/L formed the basis for the development of a diagnostic pathway for patients with suspected acute coronary syndrome. In a cohort study of 1,218 patients with suspected acute coronary syndrome who underwent high-sensitivity cardiac troponin I measurement at presentation, 3 and 6 or 12 hours, I derived and validated a novel pathway (rule out myocardial infarction if < 5 ng/L at presentation, or change < 3 ng/L and < 99th centile at 3 hours), and compared this with the established European Society of Cardiology 3-hour pathway (rule out myocardial infarction if < 99th centile at presentation, or at 3 hours if symptoms < 6 hours). The primary outcome was a comparison of the negative predictive value (NPV) of both pathways for myocardial infarction or cardiac death at 30 days. The primary outcome was evaluated in pre-specified subgroups stratified by age, gender, time of symptom onset and known ischaemic heart disease. In those < 99th centile at presentation, the ESC pathway ruled out myocardial infarction in 28.1% (342/1,218) and 78.9% (961/1,218) at presentation and 3 hours respectively, missing 18 index and two 30-day events (NPV 97.9%, 95% confidence intervals [CI] 96.9-98.7%). The novel pathway ruled out 40.7% (496/1,218) and 74.2% (904/1,218) at presentation and 3 hours, missing two index and two 30-day events (NPV 99.5%, 95% CI 99.0-99.9%; P < 0.001 for comparison). The NPV of the novel pathway was greater than the ESC pathway overall (P < 0.001), and in all subgroups including those presenting early or known to have ischaemic heart disease. There are a number of additional approaches for the rule out of myocardial infarction. Clinical risk scores apply conventional risk factors to estimate the probability of myocardial infarction. The most widely implemented scores, HEART, EDACS, GRACE and TIMI, have been extensively validated when used alongside contemporary troponin assays, however, their impact on pathways applying high-sensitivity cardiac troponin testing is less clear. In 1,935 patients with suspected acute coronary syndrome, I evaluated the safety and efficacy of our novel pathway or the European Society of Cardiology 3-hour pathway alone, or in conjunction with low-risk TIMI (0 or 1), GRACE (≤108), EDACS (< 16) or HEART (≤3) scores. Myocardial infarction or cardiac death at 30-days occurred in 14.3% (276/1,935). The ESC pathway ruled out 70% with 27 missed events giving a negative predictive value (NPV) of 97.9% (95% confidence interval [CI], 97.1 to 98.6%). Addition of a HEART score ≤3 reduced the proportion ruled out by the ESC pathway to 25%, but improved the NPV to 99.7% (95%CI 99.0 to 100%, P < 0.001). The novel pathway ruled out 65% with three missed events for a NPV of 99.7% (95%CI 99.4 to 99.9%). No risk score improved the NPV, but all reduced the proportion ruled out (24-47%, P < 0.001 for all). Whilst myocardial infarction due to atherosclerotic plaque rupture and thrombosis (type 1) is well described, the natural disease course of myocardial infarction due to oxygen supply-demand imbalance without atherothrombosis (type 2) is poorly understood. I aimed to define long-term outcomes and explore risk stratification in patients with type 2 myocardial infarction and myocardial injury. Consecutive patients (n=2,122) with elevated cardiac troponin I concentrations (≥0.05 μg/L) were identified at a tertiary cardiac centre. All diagnoses were adjudicated as per the Universal Definition of Myocardial Infarction. The primary outcome was all-cause death. Secondary outcomes included major adverse cardiovascular events (MACE; non-fatal myocardial infarction or cardiovascular death) and non-cardiovascular death. To explore competing risks, cause-specific hazard ratios were obtained using Cox regression models. The adjudicated index diagnosis was type 1 or type 2 myocardial infarction or myocardial injury in 1,171 (55.2%), 429 (20.2%) and 522 (24.6%) patients, respectively. At five years, all-cause death rates were higher in those with type 2 myocardial infarction (62.5%) or myocardial injury (72.4%) compared with type 1 myocardial infarction (36.7%). The majority of excess deaths in those with type 2 myocardial infarction or myocardial injury were due to non-cardiovascular causes (HR 2.32, 95%CI 1.92-2.81, versus type 1 myocardial infarction). Despite this, the observed crude MACE rates were similar between groups (30.6% versus 32.6%), with differences apparent after adjustment for co-variates (HR 0.82, 95%CI 0.69-0.96). Coronary heart disease was an independent predictor of MACE in those with type 2 myocardial infarction or myocardial injury (HR 1.71, 95%CI 1.31-2.24). Patients with type 2 myocardial infarction were less likely to receive secondary prevention therapy, suggesting a treatment gap may exist and there may be potential to modify clinical outcomes. A risk stratification threshold has been defined using high-sensitivity cardiac troponin I which identifies patients at very low risk of myocardial infarction or cardiac death. A diagnostic pathway incorporating this risk stratification threshold appears safer than established guidelines which apply the 99th centile alone. The use of clinical risk scores does not appear to improve the safety of this approach, however, does significantly reduce efficacy. Overall, these findings demonstrate the potential of high-sensitivity cardiac troponin testing to improve the efficiency of the assessment of patients with suspected acute coronary syndrome without compromising patient safety. The observations in those with myocardial injury and infarction have identified a phenotype of patients with type 2 myocardial infarction and coronary artery disease who are at increased cardiovascular risk, and who may benefit from targeted secondary prevention. The studies presented will inform the design of future clinical trials, and may inform international guidelines for the assessment of patients with suspected acute coronary syndrome.

L'objectif de cette thèse était de développer un magnétomètre à force de Faraday pour mesurer des valeurs absolues de l'aimantation à très basse température (30 mK) et fort champ magnétique (16 T) avec une haute sensibilité (10-5 emu). Ce magnétomètre sera principalement utilisé pour sonder les propriétés induites sous champ dans les systèmes magnétiques frustrés.Dans une première partie, je détaille le développement de ce magnétomètre. Cela comprend l'optimisation du réfrigérateur à dilution et de bobines de gradient de champ ainsi que le développement d'une détection capacitive avec un étage amplificateur à froid pour améliorer la sensibilité de la mesure. Les mesures magnétiques préliminaires sont présentées. Les changements nécessaires pour rendre le magnétomètre opérationnel sont discutés.Dans une seconde partie, je présente l'étude expérimentale de systèmes magnétiques frustrés: des grenats de Gadolinium, décrits par des spins classiques, et des composés moléculaires frustrés à base de Cuivre, pour sonder les effets quantiques. Ces mesures ont été réalisées entre 70 mK et 300 K sur les magnétomètres existant à l'Institut Néel.Dans Gd3Ga5O12, nous avons complété le diagramme de phases H-T. Nous avons montré la robustesse de ce diagramme de phases par notre étude sur le composé isomorphe GGd3Al5O12. Nous avons mis en évidence la convergence de toutes les phases observées en un unique point dans les deux systèmes.Dans les systèmes quantiques, nous avons réalisé des études préliminaires sur des clusters Cu44 à base de tétraèdres, et un système triangulaire Cu3. Bien que prometteuses, nous n'avons pas approfondi ces études à cause de problèmes d'échantillons. / The objective of this work was to develop a Faraday force magnetometer to measureabsolute values of the magnetization at very low temperatures (30 mK) andhigh applied magnetic fields (16 T) with a high sensitivity (10-5 emu). This magnetometer will be especially dedicated to the study of the field induced properties of frustrated magnets.In a first part, I present the development of this magnetometer. It involves the optimization of the dilution refrigerator and field gradient coils, and the development of a capacitive detection with a cold amplifier stage to improve the measurement sensitivity. Preliminary magnetic measurements are shown. The changes in the design required to make the magnetometer operational are discussed.In a second part, I focus on experimental studies of frustrated magnets: Gadolinium garnets, described by classical spins, and Copper based frustrated molecular compounds, to probe quantum effects. These measurements were performed from 70 mK to 300 K, with the existing magnetometers at the Institut Neel.In Gd3Ga5O12, we have complemented the H-T phase diagram. This phase diagram was proven to be robust by our study on the isomorphous compound, Gd3Al5O12. We evidence the convergence of all the observed phases to a unique point in both samples.In quantum systems, we performed preliminary studies on Cu44 clusters with tetrahedral motives, and on a triangular system Cu3. Although promising, these studies were not pursued due to sample problems.

A eficácia de métodos convencionais de transmissão, utilizados para medir absorção de materiais altamente transparentes, é geralmente limitada pela reflexão e espalhamento de luz. A espectroscopia de Lente Térmica, por outro lado, não é sensível a esses fenômenos, e tem sido amplamente usada na determinação de baixas absorções ópticas. Neste trabalho, estudamos uma configuração de Lente Térmica de duplo feixe (onda contínua cw), desenvolvida recentemente, e suas aplicações. Essa configuração otimiza a técnica de Lente Térmica, e aumenta significativamente a sensibilidade de medida. Foram realizados alguns cálculos computacionais e testes experimentais dessa configuração, e os resultados foram comparados com os de outra configuração, tradicionalmente utilizada, denominada de feixe duplo no modo-descasado. Várias aplicações foram feitas para líquidos e sólidos. Como resultado, obtivemos o espectro de absorção da água pura entre 350 e 528 nm, que indicou um valor mínimo de aproximadamente 1,5 &#8226 10-5 cm-1 em torno de 380 nm, que é mais baixo do que todos os valores da literatura. Coeficientes tão baixos quanto 2 &#8226 10-7 cm-1 podem ser medidos para a água, com 1W de potência, utilizando essa configuração otimizada. Estimamos um limite de detecção de ~ 6 &#8226 10-9 cm-1 (P = 1 W) para o solvente CCl4, que corresponde (até onde sabemos) ao menor valor já encontrado na literatura para líquidos, utilizando-se laser cw. Quanto à detecção de traços de impurezas, o limite para o Cr (III) em solução aquosa foi de ~ 40 ppb (ng/mL) em 514 nm, que corresponde a aproximadamente metade da concentração máxima ideal de Cr (III) em águas potáveis e naturais. Foram obtidos alguns resultados preliminares para a variação do caminho óptico com a temperatura (ds/dT), em sólidos com diferentes geometrias. Para a sílica fundida (quartzo vítreo) Suprasil, determinamos um limite superior para o coeficiente de absorção, cujos valores, 1 &#8226 10-6 cm-1 (em 493 nm) e 1 &#8226 10-5 cm-1 (em 355 nm), também são menores do que os resultados da literatura nessa região do espectro. A alta sensibilidade da técnica permitiu obter a absorção, em 1064 nm, das matrizes de materiais laser dopados com Nd3+, sendo (1,8 &#177 0,1) &#8226 10-3 cm-1 para o vidro Q-98 (Kigre), e (5 &#177 1 &#8226 10-4 cm-1 para o cristal Nd:YAG. Realizamos também medidas de eficiência quântica de fluorescência em nanocristais semicondutores (CdSe/ZnS) suspensos em THF e tolueno, com resultado aproximadamente 5 vezes mais preciso do que o obtido por técnica convencional de fluorescência. As principais vantagens da configuração otimizada, em relação à tradicional, são: um procedimento experimental simples, boa precisão nas medidas de difusividade térmica e, principalmente, a alta sensibilidade da técnica. As desvantagens são: um tempo de medida mais longo, e a necessidade de amostras maiores. / The efficiency of conventional transmission methods used to measure absorption of hightransparent materials is usually limited by light scattering and reflection. On the other hand, Thermal Lens spectroscopy is insensible to such phenomena and has been widely applied to determinate low optical absorptions. In this thesis, we have studied a recently developed dualbeam (continuous wave - cw) Thermal Lens configuration as well as its practical applications. This configuration optimizes the technique and significantly improves the measurement sensitivity. Some computational calculations and experimental tests of this approach were carried out. The results were compared with those obtained using a traditional configuration, named Mode-mismatched Dual-beam Thermal Lens. Several applications were made for liquids and solids. As a result, we obtained the absorption spectrum for pure water in the range of 350 to 528 nm, which indicated a minimal value of approximately 1,5 &#8226 10-5 cm-1 around 380 nm, that is lower than those found in literature. Absorption coefficients as small as 2 &#8226 10-7 cm-1, can be measured for water, using 1W of excitation power, with this optimized configuration. We have estimated a detection limit of ~ 6 &#8226 10-9 cm-1 (P = 1 W) for CCl4 solvent, which corresponds (to the best of our knowledge) to the smallest value found in the literature for liquids using cw laser. With regard to the chemical trace analysis, the detection limit was ~ 40 ppb (ng/mL) at 514 nm for Cr (III) in aqueous solutions, which is nearly half of the maximum desired Cr (III) concentration in drinking and natural waters. Some preliminary results for the temperature coefficient of the optical path length (ds/dT) were obtained at solids with different geometries. For the fused-silica (vitreous quartz) Suprasil, we have determined an upper limit for the absorption coefficient, whose values, 1 &#8226 10-6 cm-1 at 493 nm, and 1 &#8226 10-5 cm-1 at 355 nm, also are lower than the values found in literature in this spectrum region. The high sensitivity of the technique allowed us to measure the absorption (at 1064 nm) of matrices of Nd3+ doped laser materials: (1,8 &#177 0,1) &#8226 10-3 cm-1 for Q-98 glass (Kigre), and (5 &#177 1) &#8226 10-4 cm-1 for Nd:YAG crystal. We carried out as well measurements of fluorescence quantum yield of semiconductor nanocrystals (CdSe/ZnS) suspended in THF and toluene solvents, whose result was approximately 5 times more accurate than that obtained with the conventional fluorescence technique. The main advantages of the optimized configuration are: a simple experimental procedure, a good accuracy for thermal diffusivity measurements, and most important the high sensitivity of the technique. The drawbacks are: a longer time of measurements, and the requirement of larger samples.

(1) Background: Patients with severe chronic kidney disease (CKD G4–G5) often have chronically elevated high-sensitivity cardiac troponin T (hs-cTnT) values above the 99th percentile of the upper reference limit. In these patients, optimal cutoff levels for diagnosing non-ST-elevation acute coronary syndrome (NSTE-ACS) requiring revascularization remain undefined. (2) Methods: Of 11,912 patients undergoing coronary angiography from 2012 to 2017 for suspected NSTE-ACS, 325 (3%) had severe CKD. Of these, 290 with available serial hs-cTnT measurements were included, and 300 matched patients with normal renal function were selected as a control cohort. (3) Results: In the CKD cohort, 222 patients (76%) had NSTE-ACS with indication for coronary revascularization. Diagnostic performance was high at presentation and similar to that of the control population (AUC, 95% CI: 0.81, 0.75–0.87 versus 0.85, 0.80–0.89, p = 0.68), and the ROC-derived cutoff value was 4 times higher compared to the conventional 99th percentile. Combining the ROC-derived cutoff levels for hs-cTnT at presentation and absolute 3 h changes, sensitivity increased to 98%, and PPV and NPV improved up to 93% and 86%, respectively. (4) Conclusions: In patients with severe CKD and suspected ACS, the diagnostic accuracy of hs-cTnT for the diagnosis of NSTE-ACS requiring revascularization is improved by using higher assay-specific cutoff levels combined with early absolute changes.

[pt] Esta dissertação tem por objetivo o desenvolvimento de um transdutor de pressão de alta sensibilidade, baseado nas características de fase da impedância de sensores de Magnetoimpedância Gigante. A configuração do dispositivo visa a aplicações biomédicas, tais como medições da onda de pulso arterial e de sua velocidade de propagação. Projetou-se um sistema de transdução de pressão em tensão, que contém um módulo intermediário baseado em um magnetômetro GMI. O protótipo implementado inclui uma estrutura mecânica, responsável pela transdução de pressão em campo magnético, e um circuito eletrônico, responsável pela conversão deste em uma tensão elétrica de saída. A conversão de pressão em campo magnético é feita por meio de uma fonte de campo magnético aderida a uma membrana elástica. Foram realizados estudos comparativos empregando agulhas magnetizadas e ímãs permanentes como fontes móveis de campo. Por sua vez, o elemento sensor GMI utilizado foi experimentalmente caracterizado, a fim de se obter suas curvas características de módulo e fase, em função do campo magnético. O circuito eletrônico de transdução foi projetado e avaliado de forma computacional e experimental. As principais características do mesmo são detalhadas ao longo do texto e as previsões teórico-computacionais são comparadas com os resultados experimentais obtidos. Por sua vez, parâmetros chave do protótipo desenvolvido são minuciosamente analisados, tais como: sensibilidade, linearidade e resposta em frequência. Também, avalia-se a densidade espectral de ruído do transdutor desenvolvido e estima-se sua resolução na banda de passagem. Os resultados obtidos indicam que o protótipo de baixo custo desenvolvido apresenta alta resolução e alta sensibilidade, além de uma banda de passagem compatível com a requerida pelas aplicações biomédicas nas quais deseja-se empregá-lo. Dessa forma, espera-se que o dispositivo desenvolvido contribua para o avanço tecnológico do ferramental utilizado no setor da saúde. / [en] This dissertation aims at the development of a high sensitivity pressure transducer, based on the phase impedance characteristics of Giant Magnetoimpedance sensors. The configuration is intended to employ the developed device in biomedical applications, such as in measurements of arterial pulse wave and pulse wave velocity. A transduction system of pressure into voltage was designed, which contains an intermediate module based on a GMI magnetometer. The idealized prototype contains a mechanical structure, responsible for converting pressure into magnetic field, and an electronic circuit, responsible for converting the latter into a voltage output. The conversion of pressure into magnetic field is performed by means of a magnetic field source adhered to an elastic membrane. Comparative studies were carried out using magnetized needles and permanent magnets as field sources. In turn, the GMI sensor element was experimentally characterized in order to evaluate how its impedance magnitude and phase are affected by the magnetic field. The influence of the cable length used to interconnect the GMI sensor to the electronic circuit is also discussed. The electronic transduction circuit was designed and analyzed by computational and experimental evaluations. The main features of the circuit are detailed throughout the text and the theoretical and computational predictions are compared with the obtained experimental results. Furthermore, the key parameters of the developed prototype are meticulously analyzed, such as: sensitivity, linearity and frequency response. Also, the spectral noise density of the developed transducer is evaluated and its resolution in the passband is estimated. The obtained results indicate that the developed prototype presents low cost of manufacture and operation, high resolution, high sensitivity and a passband compatible with the requirements imposed by the biomedical applications of interest. In this way, it is intended that the device developed in the present Dissertation contributes to the technological enhancement of measurement equipment used in health sector.

[pt] Esta Tese teve por objetivo desenvolver um magnetômetro de alta sensibilidade, baseado nas características de fase do efeito da Magnetoimpedância Gigante (GMI – Giant Magnetoimpedance), para medição de campos magnéticos ultra-fracos. Elementos sensores GMI apresentam grande potencial na fabricação de magnetômetros que conciliem alta sensibilidade e elevada resolução espacial com baixo custo. A otimização da sensibilidade do transdutor magnético é diretamente afetada pela sensibilidade de seus elementos sensores GMI, cuja maximização é um processo intrinsecamente multivariável. Consequentemente, a metodologia experimental empregada iniciou-se pelo desenvolvimento de um sistema automático de caracterização das amostras GMI, de modo a se garantir a agilidade do processo de caracterização, possibilitando a obtenção de um volume significativo de informações experimentais. A análise minuciosa dos dados provenientes das medições experimentais permitiu a definição do ponto ótimo de operação das amostras GMI estudadas. Em todas as medições experimentais realizadas foram obtidas e avaliadas as curvas de histerese das amostras GMI. Na sequência, foram idealizados circuitos eletrônicos para condicionamento das amostras GMI e leitura das características de fase de sua impedância, destacandose a configuração eletrônica desenvolvida para a amplificação da sensibilidade de fase. Foram, inclusive, depositadas patentes nacionais e internacionais referentes ao método proposto e ao novo transdutor magnético GMI (PI 0902770-0; PI 1004686-0; WO/2010/094096 e WO/2012/048395). As caracterizações e ensaios experimentais realizados indicaram a eficácia da abordagem proposta, evidenciando o grande potencial do magnetômetro GMI desenvolvido, o qual apresentou uma elevada sensibilidade de 5 mV/nT. A resolução do magnetômetro foi limitada pelo ruído magnético ambiental, indicando que sua capacidade de medição de campos inferiores aos níveis de ruído poderá ser claramente evidenciada quando for avaliada em ambiente magneticamente blindado. Os estudos teórico-experimentais realizados indicam o potencial do transdutor magnético GMI desenvolvido, caracterizado por seu baixo custo e elevada sensibilidade, para aplicação na medição de campos magnéticos ultra-fracos. / [en] This Thesis aimed at developing a high sensitivity magnetometer, based on the phase characteristics of the Giant Magnetoimpedance effect (GMI), for measuring ultra-weak magnetic fields. GMI sensor elements have great potential to implement magnetometers that combine high sensitivity and high spatial resolution with low cost. The optimization of the magnetic transducer sensitivity is directly affected by the sensitivity of its GMI sensor elements, whose maximization is inherently multivariate. Consequently, the first step of the experimental methodology employed was to develop an automatic system for the characterization of GMI samples, so as to ensure the agility of the characterization process, allowing the gathering of a significant amount of experimental data. A thorough analysis of the experimental data led to the definition of the optimal operation point of the analyzed GMI samples. The hysteresis curves of the GMI samples were obtained and evaluated, in all of the performed experimental measurements. Based on the characterization studies results, electronic circuits were designed for conditioning the GMI samples and reading their impedance phase characteristics, highlighting the new electronic configuration developed for enhancing the phase sensitivity. National and international patents were filed, related to the proposed method, for sensitivity enhancement, and to the new GMI magnetometer (PI 0902770-0; PI 1004686-0; WO/2010/094096 e WO/2012/048395). The performed experimental characterizations and assays indicated the effectiveness of the proposed approach, showing the great potential of the developed GMI magnetometer, which presents a high sensitivity of 5 mV/nT. The magnetometer resolution was limited by the environmental magnetic noise, pointing out their capability in measuring fields below the environmental noise level, which can be clearly evidenced only when evaluated in a magnetically shielded room. The theoretical and experimental studies carried out indicate the potential of the developed GMI magnetic transducer, characterized by its low cost and high sensitivity, for applications involving the measurement of ultra-weak magnetic fields.