Control of flexure in large astronomical spectrographs

This thesis describes the design, construction and testing of an experimental system for improving the imaging stability on the detectors of the Intermediate-dispersion Spectroscopic and Imaging System (ISIS), a Cassegrain spectrograph at the 4.2 metre William Hershel Telescope. This system, called ISAAC (ISIS Spectrograph Automatic Active Collimator) is based on the new concept of active compensation, where spectrum shifts, due to the spectrograph flexing under the effect of gravity, are compensated by the movement of an active optical element. ISAAC is a fine steering tip-tilt collimator mirror. The thesis provides an extensive introduction on astronomical spectrographs, active optics and actuator systems. The new concept of active compensation of flexure is also described. The problem of spectrograph flexure is analyzed, focusing in particular on the case of ISIS and on how an active compensation system can help to solve it. The development of ISAAC is explained, from the component specification and design, to the construction and laboratory testing. The performance and successful testing of the instrument at the William Herschel Telescope is then described in detail. The implications for the future of ISIS and of new spectrograph designs are then discussed, with particular stress on the new High Resolution Optical Spectrograph (HROS) for the 8-metre Gemini telescopes

Mechanisms of ST-segment elevation myocardial infarction in patients with atrial fibrillation, prior stenting and long-standing chronic coronary syndrome

Background: The optimal antithrombotic regimen for patients with atrial fibrillation (AF) and chronic coronary syndromes beyond 1 year after percutaneous coronary intervention (PCI) is a matter of debate. For these patients, guidelines recommend oral anticoagulation (OAC) alone, but the risk of thrombotic complications remains a concern. The aim of this study was to characterize the incidence, presentation and use of antithrombotic therapy in patients with AF, prior stenting > 12 months and new ST-segment elevation myocardial infarction (STEMI). Methods: Consecutive patients were selected from an institutional registry over a 3-year period if they matched the following criteria: 1) STEMI undergoing primary PCI; 2) AF; 3) chronic coronary syndrome with prior stenting > 12 months. Results: Among 852 consecutive STEMI patients undergoing primary PCI, the prevalence of AF was 4.1%, and 6 (0.9%) patients met all the inclusion criteria. Substantial heterogeneity in antithrombotic treatment for these patients was noted (e.g., OAC alone, OAC plus a single antiplatelet agent, no antithrombotic therapy). In 50% of patients, the STEMI episode was linked to a previously stented lesion or documented plaque. Conclusions: This case review illustrates the wide heterogeneity in antithrombotic pharmacotherapy among AF patients presenting with STEMI > 12 months after PCI. The underlying reason for STEMI is only partly related to disease progression or stent-related events. This finding suggests that multiple mechanisms of recurrence may be advocated, and are not only limited to antithrombotic therapy but may be explained by the natural history of coronary artery disease in remote vessels

Tree-ring stable isotopes and radiocarbon reveal pre- and post-eruption effects of volcanic processes on trees on Mt. Etna (Sicily, Italy)

Early detection of volcanic eruptions is of major importance for protecting human life. Ground deformation and changes in seismicity, geochemistry, petrology, and gravimetry are used to assess volcanic activity before eruptions. Studies on Mt. Etna (Italy) have demonstrated that vegetation can be affected by pre-eruptive activity before the onset of eruptions. During two consecutive years before Mt. Etna's 2002/2003 flank eruption, enhanced vegetation index (NDVI) values were detected along a distinct line which later developed into an eruptive fissure. However, the mechanisms by which volcanic activity can lead to changes in pre-eruption tree growth processes are still not well understood. We analysed ${\delta}^{13}$C, ${\delta}^{18}$O and $^{14}$C in the rings of the survived trees growing near to the line where the pre-eruptive increase in NDVI was observed in order to evaluate whether the uptake of water vapour or fossil volcanic CO2 could have contributed to the enhanced NDVI. We found a dramatic decrease in ${\delta}^{18}$O in tree rings formed before 2002/2003 in trees close to the eruption fissure, suggesting uptake of volcanic water by trees during pre-eruptive magma degassing. Moist conditions caused by outgassing of ascending magma may also have led to an observed reduction in tree-ring ${\delta}^{13}$C following the eruption. Furthermore, only ambiguous evidence for tree uptake of degassed CO2 was found. Our results suggest that additional soil water condensed from degassed water vapour may have promoted photosynthesis, explaining local increases in NDVI before the 2002/2003 Mt. Etna flank eruption. Tree-ring oxygen stable isotopes might be used as indicators of past volcanic eruptions

Mechanisms of ST-segment elevation myocardial infarction in patients with atrial fibrillation, prior stenting and long-standing chronic coronary syndrome

Background: The optimal antithrombotic regimen for patients with atrial fibrillation (AF) and chronic coronary syndromes beyond 1 year after percutaneous coronary intervention (PCI) is a matter of debate. For these patients, guidelines recommend oral anticoagulation (OAC) alone, but the risk of thrombotic complications remains a concern. The aim of this study was to characterize the incidence, presentation and use of antithrombotic therapy in patients with AF, prior stenting > 12 months and new ST-segment elevation myocardial infarction (STEMI). Methods: Consecutive patients were selected from an institutional registry over a 3-year period if they matched the following criteria: 1) STEMI undergoing primary PCI; 2) AF; 3) chronic coronary syndrome with prior stenting > 12 months. Results: Among 852 consecutive STEMI patients undergoing primary PCI, the prevalence of AF was 4.1%, and 6 (0.9%) patients met all the inclusion criteria. Substantial heterogeneity in antithrombotic treatment for these patients was noted (e.g., OAC alone, OAC plus a single antiplatelet agent, no antithrombotic therapy). In 50% of patients, the STEMI episode was linked to a previously stented lesion or documented plaque. Conclusions: This case review illustrates the wide heterogeneity in antithrombotic pharmacotherapy among AF patients presenting with STEMI > 12 months after PCI. The underlying reason for STEMI is only partly related to disease progression or stent-related events. This finding suggests that multiple mechanisms of recurrence may be advocated, and are not only limited to antithrombotic therapy but may be explained by the natural history of coronary artery disease in remote vessels

Towards the introduction of the ‘Immunoscore’ in the classification of malignant tumours

The American Joint Committee on Cancer/Union Internationale Contre le Cancer (AJCC/UICC) TNM staging system provides the most reliable guidelines for the routine prognostication and treatment of colorectal carcinoma. This traditional tumour staging summarizes data on tumour burden (T), the presence of cancer cells in draining and regional lymph nodes (N) and evidence for distant metastases (M). However, it is now recognized that the clinical outcome can vary significantly among patients within the same stage. The current classification provides limited prognostic information and does not predict response to therapy. Multiple ways to classify cancer and to distinguish different subtypes of colorectal cancer have been proposed, including morphology, cell origin, molecular pathways, mutation status and gene expression-based stratification. These parameters rely on tumour-cell characteristics. Extensive literature has investigated the host immune response against cancer and demonstrated the prognostic impact of the in situ immune cell infiltrate in tumours. A methodology named ‘Immunoscore’ has been defined to quantify the in situ immune infiltrate. In colorectal cancer, the Immunoscore may add to the significance of the current AJCC/UICC TNM classification, since it has been demonstrated to be a prognostic factor superior to the AJCC/UICC TNM classification. An international consortium has been initiated to validate and promote the Immunoscore in routine clinical settings. The results of this international consortium may result in the implementation of the Immunoscore as a new component for the classification of cancer, designated TNM-I (TNM-Immune). © 2013 The Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

Contributions of mean and shape of blood pressure distribution to worldwide trends and variations in raised blood pressure: A pooled analysis of 1018 population-based measurement studies with 88.6 million participants

© The Author(s) 2018. Background: Change in the prevalence of raised blood pressure could be due to both shifts in the entire distribution of blood pressure (representing the combined effects of public health interventions and secular trends) and changes in its high-blood-pressure tail (representing successful clinical interventions to control blood pressure in the hypertensive population). Our aim was to quantify the contributions of these two phenomena to the worldwide trends in the prevalence of raised blood pressure. Methods: We pooled 1018 population-based studies with blood pressure measurements on 88.6 million participants from 1985 to 2016. We first calculated mean systolic blood pressure (SBP), mean diastolic blood pressure (DBP) and prevalence of raised blood pressure by sex and 10-year age group from 20-29 years to 70-79 years in each study, taking into account complex survey design and survey sample weights, where relevant. We used a linear mixed effect model to quantify the association between (probittransformed) prevalence of raised blood pressure and age-group- and sex-specific mean blood pressure. We calculated the contributions of change in mean SBP and DBP, and of change in the prevalence-mean association, to the change in prevalence of raised blood pressure. Results: In 2005-16, at the same level of population mean SBP and DBP, men and women in South Asia and in Central Asia, the Middle East and North Africa would have the highest prevalence of raised blood pressure, and men and women in the highincome Asia Pacific and high-income Western regions would have the lowest. In most region-sex-age groups where the prevalence of raised blood pressure declined, one half or more of the decline was due to the decline in mean blood pressure. Where prevalence of raised blood pressure has increased, the change was entirely driven by increasing mean blood pressure, offset partly by the change in the prevalence-mean association. Conclusions: Change in mean blood pressure is the main driver of the worldwide change in the prevalence of raised blood pressure, but change in the high-blood-pressure tail of the distribution has also contributed to the change in prevalence, especially in older age groups

Height and body-mass index trajectories of school-aged children and adolescents from 1985 to 2019 in 200 countries and territories: a pooled analysis of 2181 population-based studies with 65 million participants

Summary Background Comparable global data on health and nutrition of school-aged children and adolescents are scarce. We aimed to estimate age trajectories and time trends in mean height and mean body-mass index (BMI), which measures weight gain beyond what is expected from height gain, for school-aged children and adolescents. Methods For this pooled analysis, we used a database of cardiometabolic risk factors collated by the Non-Communicable Disease Risk Factor Collaboration. We applied a Bayesian hierarchical model to estimate trends from 1985 to 2019 in mean height and mean BMI in 1-year age groups for ages 5–19 years. The model allowed for non-linear changes over time in mean height and mean BMI and for non-linear changes with age of children and adolescents, including periods of rapid growth during adolescence. Findings We pooled data from 2181 population-based studies, with measurements of height and weight in 65 million participants in 200 countries and territories. In 2019, we estimated a difference of 20 cm or higher in mean height of 19-year-old adolescents between countries with the tallest populations (the Netherlands, Montenegro, Estonia, and Bosnia and Herzegovina for boys; and the Netherlands, Montenegro, Denmark, and Iceland for girls) and those with the shortest populations (Timor-Leste, Laos, Solomon Islands, and Papua New Guinea for boys; and Guatemala, Bangladesh, Nepal, and Timor-Leste for girls). In the same year, the difference between the highest mean BMI (in Pacific island countries, Kuwait, Bahrain, The Bahamas, Chile, the USA, and New Zealand for both boys and girls and in South Africa for girls) and lowest mean BMI (in India, Bangladesh, Timor-Leste, Ethiopia, and Chad for boys and girls; and in Japan and Romania for girls) was approximately 9–10 kg/m2. In some countries, children aged 5 years started with healthier height or BMI than the global median and, in some cases, as healthy as the best performing countries, but they became progressively less healthy compared with their comparators as they grew older by not growing as tall (eg, boys in Austria and Barbados, and girls in Belgium and Puerto Rico) or gaining too much weight for their height (eg, girls and boys in Kuwait, Bahrain, Fiji, Jamaica, and Mexico; and girls in South Africa and New Zealand). In other countries, growing children overtook the height of their comparators (eg, Latvia, Czech Republic, Morocco, and Iran) or curbed their weight gain (eg, Italy, France, and Croatia) in late childhood and adolescence. When changes in both height and BMI were considered, girls in South Korea, Vietnam, Saudi Arabia, Turkey, and some central Asian countries (eg, Armenia and Azerbaijan), and boys in central and western Europe (eg, Portugal, Denmark, Poland, and Montenegro) had the healthiest changes in anthropometric status over the past 3·5 decades because, compared with children and adolescents in other countries, they had a much larger gain in height than they did in BMI. The unhealthiest changes—gaining too little height, too much weight for their height compared with children in other countries, or both—occurred in many countries in sub-Saharan Africa, New Zealand, and the USA for boys and girls; in Malaysia and some Pacific island nations for boys; and in Mexico for girls. Interpretation The height and BMI trajectories over age and time of school-aged children and adolescents are highly variable across countries, which indicates heterogeneous nutritional quality and lifelong health advantages and risks