An electron multiplier has been developed which has increased the sensitivity of an existing mass spectrometer toy a factor of 10^5. This increased sensitivity has permitted determination of fission yields of substances that have undergone little fission. Two such samples, for which the rare gas isotopes have been analysed, are Bohemian pitchblende and the products resulting from the neutron fission of Th232, The Bohemian ore exhibited more neutron fission than any uranium deposit previously analysed. An explanation of this effect may be obtained by considera­tion of the geological and chemical nature of the deposit. The neutron fission of thorium, which shows fine structure in both the xenon and krypton regions, is similar to the patterns of u235 U235 and pu239, / Thesis / Master of Science (MS)

Objective: To evaluate whether abnormal concentrations in cardiac and inflammatory biomarkers could predict reductions in left ventricular ejection fraction (LVEF) for cancer patients undergoing curative treatment. Materials and Methods: Longitudinal testing was performed for high-sensitivity cardiac troponin I (hs-cTnI), N-terminal pro-B-type natriuretic peptide (NT-proBNP), heart-type fatty acid binding protein (H-FABP) and C-reactive protein (CRP) in HER2+ breast cancer (BC) patients receiving adjuvant trastuzumab treatment (n=22) and in lymphoma patients treated with radiotherapy (n=4). Sex-specific and overall upper limit of normal (ULN) cutoffs were used to identify abnormal results with a reduction in LVEF (<50% and decrease of ≥10% from baseline) indicative of cardiotoxicity. A secondary analysis was performed on the BC patients with normal LVEFs (n=12 with baseline prior to chemotherapy through to 6-months on trastuzumab) with 15 blood collections spaced between 6- and 254-days post-baseline LVEF measurement. Results: A majority of the BC patients had evidence of myocardial injury (hs-cTnI >female ULN=90%) or myocardial dysfunction (NT-proBNP >overall ULN=91%) at any timepoint with fewer patients having abnormal CRP or H-FABP concentrations (H-FABP >ULN=14%; CRP >ULN=45%). Myocardial injury and dysfunction were most evident during the first two cycles of trastuzumab treatment, with myocardial injury also evident during this early timeframe in the female lymphoma patients (3 with hs-cTnI >ULN). In the 12 patients who completed trastuzumab with normal LVEFs (median=60% at 6-months), myocardial injury (hs-cTnI >ULN) and dysfunction (NT-proBNP >ULN) was evident in >50% of patients. Four of the 22 patients did develop cardiotoxicity, but there was no difference in biomarker concentrations between patients with or without cardiotoxicity. Conclusion: The use of the recommended ULN cutoffs identified myocardial injury and dysfunction in a majority of cancer patients in this setting. Biomarker assessments did not relate to cardiac functional imaging studies. Future studies are warranted to assess different cutoffs or biomarker combinations for predicting cardiotoxicity. / Thesis / Master of Science (MSc)

Physical activity is a useful tool in the prevention of many diseases. Hospitalization after strenuous exercise from cardiac or noncardiac causes, even in young athletes without previous symptoms, can occur. These situations are not uncommon and e.g. after completing a half- marathon clinical symptoms suspicious from cardiac etiology can be present. Limitations of biomarkers used in daily clinical practice can lead to misinterpretation with additional consequences to the patient's outcome. Our goal was to describe changes of markers used in daily clinical practice after extreme physical activity and after exercise under laboratory conditions. We performed two studies in cooperation with Department of cardiology and Department of sports medicine. The goal of our first study was to examine high sensitivity troponin I (hsTnI), galectin-3, cystatin C, NGAL and ultrasensitive CRP (uCRP) after extremely long run during the competition in long distance running. The goal of our second study was to examine high- sensitivity troponin T (hsTnT) and hsTnI, creatinine and cystatin C, and urine albumin and NGAL after a standardized two-hour treadmill run under laboratory conditions and to find possible connection with echocardiographic, laboratory and other assessed parameters. The second goal of study under laboratory...

Background: Kawasaki disease (KD) affects mainly children younger than five years of age, leading to coronary artery lesions, and even to life-threatening myocardial infarctions. Since 1976, Kawasaki disease has occurred among thousands of children in Taiwan. Evidence suggests that inflammation plays a key role in the pathogenesis of atherosclerosis. Significant determinants of high sensitivity C-reactive protein (hs-CRP), which is a sensitive indicator of inflammation, as well as white blood cell (WBC) count, and high-density lipoprotein cholesterol (HDLc) and coronary artery lesion were identified. The relationships between these factors¡¦ concentration and arterial lesion were likewise investigated and had reported. The aim of this study was to determine the serum levels of the hs-CRP, WBC count, and plasma HDLc levels in patients with later phase of KD. Methods and Materials: From July 2005 to June 2006, 97 children with Kawasaki disease at least 1 year after diagnosis were recruited in this study. These participated children had been diagnosed as KD and collected at the interval of 2001 to 2004. Diagnosis was based on the 1984 revised by the KD Research Committee in Japan. The participants were grouped into 45 patients with KD and coronary aneurysms (Group I), 52 patients with KD and normal coronary arteries (Group II), and 50 healthy age-matched children (Control Group III). Their WBC count, systemic and diastolic blood pressures, body mass index, age, sex, fasting total cholesterol concentrations, triglyceride, high-density lipoprotein cholesterol (HDLc), low-density lipoprotein cholesterol, serum hs-CRP levels, and coronary artery lesion by cardioechography were recorded and compared. The analytical differences between hs-CRP, WBC count, and plasma HDLc levels and the coronary artery events in KD were examined. Results: Serum hs-CRP levels of Group I patients (mean 0.264 mg/dl) was significantly greater than that of Group II (mean 0.155 mg/dl, p=0.006) and Group III patients (mean 0.116 mg/dl, p =0.017). Similarly, the WBC count of Group I patients (mean 6,543.11/mm3) was significantly greater than that of Group II (mean 5,720.19/mm3, p=0.029), and Group III patients (mean 5,611.27/mm3, p =0.012). However, plasma HDLc levels of Group I patients (mean 41.42 mg/dl) was significantly lesser than that of Group II (mean 44.79 mg/dl, p=0.035), and Control Group III patients (mean 46.58 mg/dl, p=0.027). There was a positive association between hs-CRP and WBC count levels (r = 0.641, p < 0.05), but none between hs-CRP and plasma HDLc levels. Conclusions: There is the possibility of ongoing low-grade inflammation late after the convalescent phase of Kawasaki disease in children with coronary aneurysms, which may have a role in increasing coronary artery dysfunction. These results also suggest that hs-CRP, WBC count, and plasma HDLc levels are useful parameters for predicting formation of coronary artery lesion even in children after onset of KD.

Photophysical characterization of several species of fluorescent silver nanoclusters, encapsulated in oligonucleotide scaffolds, was achieved at the bulk and single molecule level. These studies reveal the presence of a short-lived microsecond blinking component which leads to higher emission rates than exhibited by common organic dyes. This dark state was found to be photo-accessible with a very efficient depopulation transition leading to repopulation of the emissive state. Secondary excitation on resonance with this transition significantly shortens the residence time in the dark state giving rise to as much as 5-fold fluorescence enhancement. Manipulation of the secondary laser can be used to impose a regularly modulated waveform onto the fluorescent signal. Signal processing techniques can be employed to extract the modulated signal from large backgrounds, leading to drastically improved sensitivity. This new imaging concept can be extended, beyond Ag nanoclusters, to common organic fluorophores that demonstrate large dark state quantum yields. These fluorophores simultaneously illustrate the utility of this technique and help to define a general set of parameters for engineering ideal dyes for modulated signal extraction. Ideally suited for fluorescence enhancement, FRET pairs can be used to engineer a wide range of modulatable systems, based on detecting donor emission in the presence of a laser directly exciting the acceptor. The utility of Ag nanoclusters, organic dyes, and FRET systems for improved sensitivity are investigated in this work.

Background: Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia. There is a need for new pharmacological treatment strategies since the current antiarrhythmic drugs have a modest efficacy and may have severe side effects. Cardioversion (CV) of AF offers an opportunity to study related conditions in sinus rhythm (SR) and during AF. Since catheter ablation of AF is a symptomatic treatment, it is important to have tools for measurement of arrhythmia-related symptoms. Aims: To evaluate the effect of atorvastatin on maintaining SR after CV of persistent AF. To assess if highsensitivity C-reactive protein (hsCRP) predicts the recurrence of AF after CV in a population randomized to treatment with either atorvastatin or placebo. To quantify the symptomatic effect of left atrial catheter ablation of AF. To assess if the restoration of SR by CV, in a population with persistent AF, affects sleep apnea. Methods: Paper I: A total of 234 patients were randomized to treatment with either high dose atorvastatin or placebo prior to CV. Paper II: In a pre-specified substudy which included 128 of the patients in study I, hsCRP was analyzed before and after CV. Paper III: Umea 22 Arrhythmia Questions (U22) is a questionnaire that quantifies paroxysmal tachycardia symptoms. A total of 105 patients underwent first-time pulmonary vein isolation and answered U22 forms at baseline and follow-up 304 (SD 121) days after ablation. Paper IV: Polysomnography was performed before and after CV in 23 patients with persistent AF scheduled for elective CV. Results: Paper I: An intention-to-treat analysis with the available data, by randomization group, showed that 57 (51%) in the atorvastatin group and 47 (42%) in the placebo group were in SR 30 days after CV (OR 1.44, 95%CI 0.85–2.44, P=0.18). Paper II: HsCRP did not significantly predict recurrence of AF at 30 days. However, after adjusting for treatment with atorvastatin, hsCRP predicted the recurrence of AF (OR 1.14, 95% CI 1.01–1.27). Six months after CV, hsCRP at randomization predicted recurrence of AF in both univariate analysis (OR 1.30, 95% CI 1.06–1.60) and in multivariate logistic regression analysis (OR 1.33, 95% CI 1.06– 1.67). Paper III: The U22 scores for well-being, arrhythmia as cause for impaired well-being, derived timeaspect score for arrhythmia, and discomfort during attack detected relevant improvements of symptoms after the ablation. U22 showed larger improvement in patients undergoing only one procedure than in patients who later underwent repeated interventions. Paper IV: Obstructive sleep apnea occurred in 17/23 patients (74%), and central sleep apnea in 6/23 patients (26%). Five patients had both obstructive and central sleep apnea. SR at follow-up was achieved in 16 patients. The obstructive apnea-hypopnea index, central apneahypopnea index, and the number of patients with obstructive or central sleep apnea did not differ before and after restoration of SR. Conclusions: Atorvastatin is not a treatment option with regards to maintaining SR after CV in patients with persistent AF. HsCRP was associated with AF recurrence 1 and 6 months after successful CV of persistent AF. U22 quantifies the symptomatic improvement after AF ablation with adequate internal consistency and construct validity. Both obstructive and central sleep apneas are highly prevalent in patients with persistent AF. Obstructive sleep apneas are unaffected by the CV of AF to SR.

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&amp;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.

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.