The moon as a recorder of organic evolution in the early solar system: a lunar regolith analog study

The organic record of Earth older than ∼3.8 Ga has been effectively erased. Some insight is provided to us by meteorites as well as remote and direct observations of asteroids and comets left over from the formation of the Solar System. These primitive objects provide a record of early chemical evolution and a sample of material that has been delivered to Earth's surface throughout the past 4.5 billion years. Yet an effective chronicle of organic evolution on all Solar System objects, including that on planetary surfaces, is more difficult to find. Fortunately, early Earth would not have been the only recipient of organic matter–containing objects in the early Solar System. For example, a recently proposed model suggests the possibility that volatiles, including organic material, remain archived in buried paleoregolith deposits intercalated with lava flows on the Moon. Where asteroids and comets allow the study of processes before planet formation, the lunar record could extend that chronicle to early biological evolution on the planets. In this study, we use selected free and polymeric organic materials to assess the hypothesis that organic matter can survive the effects of heating in the lunar regolith by overlying lava flows. Results indicate that the presence of lunar regolith simulant appears to promote polymerization and, therefore, preservation of organic matter. Once polymerized, the mineral-hosted newly formed organic network is relatively protected from further thermal degradation. Our findings reveal the thermal conditions under which preservation of organic matter on the Moon is viable

The influence of stratospheric vortex displacements and splits on surface climate

A strong link exists between stratospheric variability and anomalous weather patterns at the earth’s surface. Specifically, during extreme variability of the Arctic polar vortex termed a “weak vortex event,” anomalies can descend from the upper stratosphere to the surface on time scales of weeks. Subsequently the outbreak of cold-air events have been noted in high northern latitudes, as well as a quadrupole pattern in surface temperature over the Atlantic and western European sectors, but it is currently not understood why certain events descend to the surface while others do not. This study compares a new classification technique of weak vortex events, based on the distribution of potential vorticity, with that of an existing technique and demonstrates that the subdivision of such events into vortex displacements and vortex splits has important implications for tropospheric weather patterns on weekly to monthly time scales. Using reanalysis data it is found that vortex splitting events are correlated with surface weather and lead to positive temperature anomalies over eastern North America of more than 1.5 K, and negative anomalies over Eurasia of up to −3 K. Associated with this is an increase in high-latitude blocking in both the Atlantic and Pacific sectors and a decrease in European blocking. The corresponding signals are weaker during displacement events, although ultimately they are shown to be related to cold-air outbreaks over North America. Because of the importance of stratosphere–troposphere coupling for seasonal climate predictability, identifying the type of stratospheric variability in order to capture the correct surface response will be necessary

Standards for plant synthetic biology: A common syntax for exchange of DNA parts

© 2015 New Phytologist Trust. Inventors in the field of mechanical and electronic engineering can access multitudes of components and, thanks to standardization, parts from different manufacturers can be used in combination with each other. The introduction of BioBrick standards for the assembly of characterized DNA sequences was a landmark in microbial engineering, shaping the field of synthetic biology. Here, we describe a standard for Type IIS restriction endonuclease-mediated assembly, defining a common syntax of 12 fusion sites to enable the facile assembly of eukaryotic transcriptional units. This standard has been developed and agreed by representatives and leaders of the international plant science and synthetic biology communities, including inventors, developers and adopters of Type IIS cloning methods. Our vision is of an extensive catalogue of standardized, characterized DNA parts that will accelerate plant bioengineering

A comprehensive high cost drugs dataset from the NHS in England - An OpenSAFELY-TPP Short Data Report

Background: At the outset of the COVID-19 pandemic, there was no routine comprehensive hospital medicines data from the UK available to researchers. These records can be important for many analyses including the effect of certain medicines on the risk of severe COVID-19 outcomes. With the approval of NHS England, we set out to obtain data on one specific group of medicines, “high-cost drugs” (HCD) which are typically specialist medicines for the management of long-term conditions, prescribed by hospitals to patients. Additionally, we aimed to make these data available to all approved researchers in OpenSAFELY-TPP. This report is intended to support all studies carried out in OpenSAFELY-TPP, and those elsewhere, working with this dataset or similar data. Methods: Working with the North East Commissioning Support Unit and NHS Digital, we arranged for collation of a single national HCD dataset to help inform responses to the COVID-19 pandemic. The dataset was developed from payment submissions from hospitals to commissioners. Results: In the financial year (FY) 2018/19 there were 2.8 million submissions for 1.1 million unique patient IDs recorded in the HCD. The average number of submissions per patient over the year was 2.6. In FY 2019/20 there were 4.0 million submissions for 1.3 million unique patient IDs. The average number of submissions per patient over the year was 3.1. Of the 21 variables in the dataset, three are now available for analysis in OpenSafely-TPP: Financial year and month of drug being dispensed; drug name; and a description of the drug dispensed. Conclusions: We have described the process for sourcing a national HCD dataset, making these data available for COVID-19-related analysis through OpenSAFELY-TPP and provided information on the variables included in the dataset, data coverage and an initial descriptive analysis.</ns4:p

Standards for plant synthetic biology: a common syntax for exchange of DNA parts.

Inventors in the field of mechanical and electronic engineering can access multitudes of components and, thanks to standardization, parts from different manufacturers can be used in combination with each other. The introduction of BioBrick standards for the assembly of characterized DNA sequences was a landmark in microbial engineering, shaping the field of synthetic biology. Here, we describe a standard for Type IIS restriction endonuclease-mediated assembly, defining a common syntax of 12 fusion sites to enable the facile assembly of eukaryotic transcriptional units. This standard has been developed and agreed by representatives and leaders of the international plant science and synthetic biology communities, including inventors, developers and adopters of Type IIS cloning methods. Our vision is of an extensive catalogue of standardized, characterized DNA parts that will accelerate plant bioengineering.Biotechnological and Biological Sciences Research Council (BBSRC). Grant Numbers: BB/K005952/1, BB/L02182X/1 Synthetic Biology Research Centre ‘OpenPlant’ award. Grant Number: BB/L014130/1 Spanish MINECO. Grant Number: BIO2013‐42193‐R Engineering Nitrogen Symbiosis for Africa (ENSA) The Bill & Melinda Gates Foundation US Department of Energy, Office of Biological and Environmental. Grant Number: DE‐AC02‐05CH1123 COST Action. Grant Number: FA100

Optimierung der Anzahl an Daten für das Trainieren von GANs (Generative Adversarial Networks) für die automatisierte Segmentation in der Strahlentherapie

Abweichender Titel nach Übersetzung der Verfasserin/des VerfassersPurpose : Radiation oncology relies on the accuracy of organ-at-risk (OAR) and target structure delineations for dose calculations and treatment planning. The effect of inaccurate structure localization is more pronounced in particle therapy due to higher dose gradients in comparison to photon therapy. Manual segmentation is the gold standard even though inter-observer-variability and temporal anatomical changes influence subsequent dose calculations. However, manual segmentation is a time-consuming task, which makes it unfeasible for adaptive radiotherapy (ART). The increased workload due to multiple replannings could, therefore, benefit from automated segmentation. In particular, deep learning methods have already been used with great success in segmentation tasks and are currently investigated for their use in medical applications. Discriminative classifiers are one such method that is typically used for image segmentation. However, they suffer from small data sets resulting in overfitting, and typical loss functions do not guarantee spatial consistency. Generative adversarial networks (GANs), on the other hand, have shown promise in tackling those issues. This thesis aimed to compare GANs with convolutional neural networks (CNNs) based on the popular U-net architecture, as a type of discriminative classifier, on different sized training data. This was done to determine a potential benefit of using GANs for segmentation in radiation oncology. Both network architectures were trained, validated, and tested on segmentations of a subset of OARs in prostate cancer patients. Methods and Materials: Data of 360 patients, who were treated for prostate cancer at the Department of Radiation Oncology at the Medical University of Vienna, was investigated. The OARs were bladder, rectum, and the femoral heads. The CNN, as well as the GAN architecture, were trained on different training data sets consisting of 1, 6, 11, 16, 21, 26, and 100 patients. An extensive hyperparameter search was performed to identify the best settings for all observed structures. The performance of the networks was evaluated using metrics such as Dice similarity coefficient (DSC), sensitivity, precision, Hausdorff distance (HD), mean squared error (MSE), and root mean squared error (RMSE).Results: No significant difference could be observed for small training data set sizes between GAN and CNN when measured with the DSC. For sensitivity and precision, the networks did perform differently for certain data set sizes and OARs. The precision score of the GAN was higher for 6, 16, and 21 patients. For 1 and 6 patients in the training data set, the CNN performed better according to sensitivity. However, the sensitivity score of the GAN was higher for 16 patients. As sensitivity and precision are associated with over- and underrepresentation, this could indicate a correcting influence of the discriminator; however, there is no discernible trend amongst all patient data set sizes. For 100 patients, no significant difference was observed between the different architectures resulting in near-identical mean DSCs of bladder, rectum, and femoral heads of 0.89 ± 0.08, 0.84 ± 0.08, and 0.93 ± 0.06, respectively.Conclusion: In this thesis, no significant difference in performance between GAN and CNN could be observed. When compared to other factors, such as network architecture and data preprocessing, it might not be worth training GANs for image segmentation.8

Hydrocarbons as recorders of cosmic environments

Hydrocarbons are ubiquitous in the Cosmos. Carbon stars jettison large amounts of hydrocarbons into interstellar space and these are incorporated into forming planetary systems alongside newly synthesized hydrocarbon material. The structure of a hydrocarbon reveals its origin with non-biological, biological, low temperature, high temperature, reduced, oxidised and aqueously altered hydrocarbons all having structural features that imply their provenance. These features are explored throughout this work, with a focus on the insoluble macromolecular organic carbon of meteorites and comparative terrestrial samples. Analytical pyrolysis of macromolecular material in meteorites is a well established technique. By subjecting samples to multiple heating steps, rather than the more usual single step, new insights into the structure and composition of the macromolecular material have been obtained. In addition, simple typing of chondrites and a reconstruction of the conditions experienced on their asteroid parent bodies is possible using the products of pyrolysis. It is the carbonaceous chondrites that have received the most attention for their organic content but some ordinary chondrites also contain appreciable quantities of organic materials. The organic inventory of both carbonaceous and ordinary chondrites has been explored in this study. Carbonaceous chondrites contain authentic abiotic organic material and are in great demand for scientific analysis and experimentation. Yet these objects are extremely rare and valuable and there is a need for analogue materials that are available in larger quantities and on which specific experiments can be carried out. Uses of effective meteorite organic analogues include the training of personnel, testing of analytical methods, contamination studies, and optimisation of space mission instruments. Most of the carbon in carbonaceous chondrites is a non-biological aromatic and intractable macromolecular material and previously unsatisfactory analogues have included coals and other so-called type III kerogens. Following a comparison of a number of candidate materials a new analogue has been identified in reworked fossil soils from the Jurassic of southern England. This type IV kerogen displays great similarities to the macromolecular material in meteorites and can be employed to lessen the burden on our curated collections of rare carbonaceous meteorites. The thermal and chemical stability of hydrocarbons ensures that they exhibit excellent preservation potential and can often be found when other molecular information carriers have long since perished. This feature is important when studying planetary environments for indicators of biogenicity. Yet there is a multitude of information to process and the organic signals can often be confusing owing to diagenesis, catagenesis, oxidation and weathering. In this study a wide range of terrestrial and extraterrestrial materials have been examined using statistical techniques to develop a method for the discrimination of abiotic from biotic macromolecular materials, based only upon the distributions of simple aromatic hydrocarbons and related compounds. This has important implications for life-detection missions destined for Mars, which are currently under development.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Temporal trends in associations between severe mental illness and risk of cardiovascular disease:A systematic review and meta-analysis

BACKGROUND: Severe mental illness (SMI; schizophrenia, bipolar disorders (BDs), and other nonorganic psychoses) is associated with increased risk of cardiovascular disease (CVD) and CVD-related mortality. To date, no systematic review has investigated changes in population level CVD-related mortality over calendar time. It is unclear if this relationship has changed over time in higher-income countries with changing treatments. METHODS AND FINDINGS: To address this gap, a systematic review was conducted, to assess the association between SMI and CVD including temporal change. Seven databases were searched (last: November 30, 2021) for cohort or case-control studies lasting ≥1 year, comparing frequency of CVD mortality or incidence in high-income countries between people with versus without SMI. No language restrictions were applied. Random effects meta-analyses were conducted to compute pooled hazard ratios (HRs) and rate ratios, pooled standardised mortality ratios (SMRs), pooled odds ratios (ORs), and pooled risk ratios (RRs) of CVD in those with versus without SMI. Temporal trends were explored by decade. Subgroup analyses by age, sex, setting, world region, and study quality (Newcastle-Ottawa scale (NOS) score) were conducted. The narrative synthesis included 108 studies, and the quantitative synthesis 59 mortality studies (with (≥1,841,356 cases and 29,321,409 controls) and 28 incidence studies (≥401,909 cases and 14,372,146 controls). The risk of CVD-related mortality for people with SMI was higher than controls across most comparisons, except for total CVD-related mortality for BD and cerebrovascular accident (CVA) for mixed SMI. Estimated risks were larger for schizophrenia than BD. Pooled results ranged from SMR = 1.55 (95% confidence interval (CI): 1.33 to 1.81, p < 0.001), for CVA in people with BD to HR/rate ratio = 2.40 (95% CI: 2.25 to 2.55, p < 0.001) for CVA in schizophrenia. For schizophrenia and BD, SMRs and pooled HRs/rate ratios for CHD and CVD mortality were larger in studies with outcomes occurring during the 1990s and 2000s than earlier decades (1980s: SMR = 1.14, 95% CI: 0.57 to 2.30, p = 0.71; 2000s: SMR = 2.59, 95% CI: 1.93 to 3.47, p < 0.001 for schizophrenia and CHD) and in studies including people with younger age. The incidence of CVA, CVD events, and heart failure in SMI was higher than controls. Estimated risks for schizophrenia ranged from HR/rate ratio 1.25 (95% CI: 1.04 to 1.51, p = 0.016) for total CVD events to rate ratio 3.82 (95% CI: 3.1 to 4.71, p < 0.001) for heart failure. Incidence of CHD was higher in BD versus controls. However, for schizophrenia, CHD was elevated in higher-quality studies only. The HR/rate ratios for CVA and CHD were larger in studies with outcomes occurring after the 1990s. Study limitations include the high risk of bias of some studies as they drew a comparison cohort from general population rates and the fact that it was difficult to exclude studies that had overlapping populations, although attempts were made to minimise this. CONCLUSIONS: In this study, we found that SMI was associated with an approximate doubling in the rate ratio of CVD-related mortality, particularly since the 1990s, and in younger groups. SMI was also associated with increased incidence of CVA and CHD relative to control participants since the 1990s. More research is needed to clarify the association between SMI and CHD and ways to mitigate this risk