Missing Value Imputation and Survival Analysis for Treatment Outcome Prediction in High-Grade GEP NEN

The objective of the thesis was to create a reliable model for outcome prediction in gastrointestinal cancers using data with incomplete variables. This was a two-step pro- cess. The first part involved analysis and review of literature on missing values, with a separate experiment conducted to support decisions. The second step involved prepro- cessing data with assistance from expert knowledge and conducting survival analysis. We found that imputing missing values is always better than discarding information in variables and samples. This is especially important with a small sample size. k-Nearest Neighbor imputation provided accurate single imputations in the experiment and had the most promising impact on the survival models. The two survival models, Coxnet and Component-Wise Gradient Boosting, provided the highest test concordance, with the latter having the lowest integrated Brier score and time-dependent Brier score We argue that the choice of model depends on the application, as a model may excel in one metric and be less effective in another metric. If the intention is accurately predicting the order of events, the model that maximizes concordance should be used. Conversely, if accurate modelling of the survival times is of interest, then the model maximizing the integrated Brier score should be used. We also found that Number of Courses, Ki-67, and NSE were identified as having the most average importance across the four survival models. Additionally, features WHO Perf Stat, Ki-67, and Albumin were identified as equally important, consistent with the results reported by Jenul et al.(2023)

Determination of the emission height profile of volcanic emissions using inverse modelling

Ved å bruke en invers metode kan høydeprofilen av svoveldioksid (SO2) utslippene fra et vulkanutbrudd estimeres. Metoden bruker satellitt observerte SO2 kolonneverdier (AIRS, OMI) og en partikkel dispersjons modell (FLEXPART) for å simulere utslipp i flere ulike høyder. Utslipp i visse høyder gir da en best match til det som er observert av satelittene. Deretter er den estimerte høydeprofilen brukt til å simulere tranporten av utslippene i flere dager etter utbruddet ved bruk av FLEXPART modellen. Sensitivitets eksperimenter for høydeprofilen er også utarbeidet

A new aerosol wet removal scheme for the Lagrangian particle model FLEXPART v10

A new, more physically based wet removal scheme for aerosols has been implemented in the Lagrangian particle dispersion model FLEXPART. It uses three-dimensional cloud water fields from the European Centre for MediumRange Weather Forecasts (ECMWF) to determine cloud extent and distinguishes between in-cloud and below-cloud scavenging. The new in-cloud nucleation scavenging depends on cloud water phase (liquid, ice or mixed-phase), based on the aerosol's prescribed efficiency to serve as ice crystal nuclei and liquid water nuclei, respectively. The impaction scavenging scheme now parameterizes below-cloud removal as a function of aerosol particle size and precipitation type (snow or rain) and intensity. Sensitivity tests with the new scavenging scheme and comparisons with observational data were conducted for three distinct types of primary aerosols, which pose different challenges for modeling wet scavenging due to their differences in solubility, volatility and size distribution: (1) Cs-137 released during the Fukushima nuclear accident attached mainly to highly soluble sulphate aerosol particles, (2) black carbon (BC) aerosol particles, and (3) mineral dust. Calculated e-folding lifetimes of accumulation mode aerosols for these three aerosol types were 11.7, 16.0, and 31.6 days respectively, when well mixed in the atmosphere. These are longer lifetimes than those obtained by the previous removal schem, and, for mineral dust in particular, primarily result from very slow in-cloud removal, which globally is the primary removal mechanism for these accumulation mode particles. Calculated e-folding lifetimes in FLEXPART also have a strong size dependence, with the longest lifetimes found for the accumulation-mode aerosols. For example, for dust particles emitted at the surface the lifetimes were 13.8 days for particles with 1 aem diameter and a few hours for 10 aem particles. A strong size dependence in below-cloud scavenging, combined with increased dry removal, is the primary reason for the shorter lifetimes of the larger particles. The most frequent removal is in-cloud scavenging (85% of all scavenging events) but it occurs primarily in the free troposphere, while below-cloud removal is more frequent below 1000m (52% of all events) and can be important for the initial fate of species emitted at the surface, such as those examined here. For assumed realistic in-cloud removal efficiencies, both BC and sulphate have a slight overestimation of observed atmospheric concentrations (a factor of 1.6 and 1.2 respectively). However, this overestimation is largest close to the sources and thus appears more related to overestimated emissions rather than underestimated removal. The new aerosol wet removal scheme of FLEXPART incorporates more realistic information about clouds and aerosol properties and it compares better with both observed lifetimes and concentration than the old scheme.Peer reviewe

Intake of farmed Atlantic salmon fed soybean oil increases insulin resistance and hepatic lipid accumulation in mice

BACKGROUND: To ensure sustainable aquaculture, fish derived raw materials are replaced by vegetable ingredients. Fatty acid composition and contaminant status of farmed Atlantic salmon (Salmo salar L.) are affected by the use of plant ingredients and a spillover effect on consumers is thus expected. Here we aimed to compare the effects of intake of Atlantic salmon fed fish oil (FO) with intake of Atlantic salmon fed a high proportion of vegetable oils (VOs) on development of insulin resistance and obesity in mice. METHODOLOGY/PRINCIPAL FINDINGS: Atlantic salmon were fed diets where FO was partly (80%) replaced with three different VOs; rapeseed oil (RO), olive oil (OO) or soy bean oil (SO). Fillets from Atlantic salmon were subsequently used to prepare Western diets (WD) for a mouse feeding trial. Partial replacement of FO with VOs reduced the levels of polychlorinated biphenyls (PCB) and dichloro-diphenyl-tricloroethanes (DDT) with more than 50% in salmon fillets, in WDs containing the fillets, and in white adipose tissue from mice consuming the WDs. Replacement with VOs, SO in particular, lowered the n-3 polyunsaturated fatty acid (PUFA) content and increased n-6 PUFA levels in the salmon fillets, in the prepared WDs, and in red blood cells collected from mice consuming the WDs. Replacing FO with VO did not influence obesity development in the mice, but replacement of FO with RO improved glucose tolerance. Compared with WD-FO fed mice, feeding mice WD-SO containing lower PCB and DDT levels but high levels of linoleic acid (LA), exaggerated insulin resistance and increased accumulation of fat in the liver. CONCLUSION/SIGNIFICANCE: Replacement of FO with VOs in aqua feed for farmed salmon had markedly different spillover effects on metabolism in mice. Our results suggest that the content of LA in VOs may be a matter of concern that warrants further investigation

The Protected Burial Mound ‘Store Vejlhøj’, Vinderup, Denmark: First Results

An archaeological excavation of the protected burial mound Store Vejlhøj in northwestern Denmark was carried out in October-November 2021. The excavation formed part of the ERC-funded research project called ANTHEA, focusing on the deep history of anthropogenic heathlands. It was conducted by Aarhus University in collaboration with Holstebro Museum and Moesgaard Museum. The aim was to test a new method of sampling pollen data from different construction stages in a burial mound and comparing them with pollen data from nearby lake sediments with a view to improving our understanding of prehistoric anthropogenic heathland dynamics. Prior to the excavation, soil cores were collected from two nearby peat sediments as well as six burial mounds (including Store Vejlhøj) within a 1 km range of Lake Skånsø, where previous pollen analyses had been carried out. Based on these preliminary corings, Store Vejlhøj was selected for further archaeological investigation. A dispensation for excavating the protected mound was granted by the Danish Palaces and Culture Agency. The excavation was based on a 5 m long trench through the barrow, moving from its foot inwards. The surface vegetation and 40 cm topsoil were removed by an excavator, after which the remainder of the trench was manually dug in horizontal layers. Observation conditions were good. The excavation revealed a series of well-defined barrow construction stages, as well as unusually wellpreserved turf structures. Only two archaeological finds could be related to the barrow, both of which were later than its initial construction: a secondary urn in the top layer, and the base of a second urn at the foot of the mound. The burial mound was constructed using a minimum of three shells, which could be observed in the trench profile. Turfs were most probably collected locally in a landscape dominated by grass pastures, where no previous turf cutting had taken place. A total of 34 soil samples were collected for paleoecological analyses (pollen, Non-Pollen Polymorphs (NPPs), macrofossils) and geoarchaeological analyses (micromorphology, bulk samples). Preliminary pollen and macrofossil results from the burial mound revealed poor preservation conditions, which prompted a trench extension of 0.5 m by 0.2 m to find better preservation conditions. This extension resulted in the collection of a single final macrofossil sample, although there was no identifiable change in the in-situ preservation conditions. The dating results of the mound have not yet been completed and will be included as appendix 4-6 in 2023

Conducting volcanic ash cloud exercises: practising forecast evaluation procedures and the pull-through of scientific advice to the London VAAC

The London Volcanic Ash Advisory Centre (VAAC) provides forecasts on the expected presence of volcanic ash in the atmosphere to mitigate the risk to aviation. It is fundamentally important that operational capability is regularly tested through exercises, to guarantee an effective response to an event. We have developed exercises which practise the pull-through of scientific advice into the London VAAC, the forecast evaluation process, and the decision-making procedures and discussions needed for generating the best possible forecasts under real-time conditions. London VAAC dispersion model forecasts are evaluated against observations. To test this capability in an exercise, we must create observation data for a hypothetical event. We have developed new methodologies for generating and using simulated satellite and lidar retrievals. These simulated observations enable us to practise our ability to interpret, compare, and evaluate model output and observation data under real-time conditions. Forecast evaluation can benefit from an understanding of how different choices of model setup (input parameters), model physics, and driving meteorological data impact the predicted extent and concentration of ash. Through our exercises, we have practised comparing output from model simulations generated using different models, model setups, and meteorological data, supplied by different institutions. Our exercises also practise the communication and interaction between Met Office (UK) scientists supporting the London VAAC and external experts, enabling knowledge exchange and discussions on the interpretation of model output and observations, as we strive to deliver the best response capability for the aviation industry and stakeholders. In this paper, we outline our exercise methodology, including the use of simulated satellite and lidar observations, and the development of the strategy to compare output generated from different modelling systems. We outline the lessons learnt, including the benefits and challenges of conducting exercises which practise our ability to provide scientific advice for an operational response at the London VAAC

The origins and spread of domestic horses from the Western Eurasian steppes

This is the final version. Available on open access from Nature Research via the DOI in this recordData availability: All collapsed and paired-end sequence data for samples sequenced in this study are available in compressed fastq format through the European Nucleotide Archive under accession number PRJEB44430, together with rescaled and trimmed bam sequence alignments against both the nuclear and mitochondrial horse reference genomes. Previously published ancient data used in this study are available under accession numbers PRJEB7537, PRJEB10098, PRJEB10854, PRJEB22390 and PRJEB31613, and detailed in Supplementary Table 1. The genomes of ten modern horses, publicly available, were also accessed as indicated in their corresponding original publications57,61,85-87.NOTE: see the published version available via the DOI in this record for the full list of authorsDomestication of horses fundamentally transformed long-range mobility and warfare. However, modern domesticated breeds do not descend from the earliest domestic horse lineage associated with archaeological evidence of bridling, milking and corralling at Botai, Central Asia around 3500 BC. Other longstanding candidate regions for horse domestication, such as Iberia and Anatolia, have also recently been challenged. Thus, the genetic, geographic and temporal origins of modern domestic horses have remained unknown. Here we pinpoint the Western Eurasian steppes, especially the lower Volga-Don region, as the homeland of modern domestic horses. Furthermore, we map the population changes accompanying domestication from 273 ancient horse genomes. This reveals that modern domestic horses ultimately replaced almost all other local populations as they expanded rapidly across Eurasia from about 2000 BC, synchronously with equestrian material culture, including Sintashta spoke-wheeled chariots. We find that equestrianism involved strong selection for critical locomotor and behavioural adaptations at the GSDMC and ZFPM1 genes. Our results reject the commonly held association between horseback riding and the massive expansion of Yamnaya steppe pastoralists into Europe around 3000 BC driving the spread of Indo-European languages. This contrasts with the scenario in Asia where Indo-Iranian languages, chariots and horses spread together, following the early second millennium BC Sintashta culture

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline