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20,7 % der 2.493 Probanden hatten eine erektile Dysfunktion, 62,9 % waren übergewichtig bzw. adipös und 57,8 % hatten einen Bauchumfang von ≥ 94 cm. Arterielle Hypertonie war mit 16,4 % der häufigste analysierte kardiovaskuläre Risikofaktor. Eine geringe körperliche Aktivität (OR: 1,38 / 95 % CI: 1,05-1,81), Diabetes Mellitus Typ 2 (OR: 2,42 / 95 % CI: 1,34-4,40) und der Bauchumfang, nach etablierten Grenzwert (OR: 1,56 / 95 % CI: 1,26-1,93) und stetig in 1 cm-Schritten (OR: 1,03 / 95 % CI: 1,02-1,03), sind signifikant mit einer erektilen Dysfunktion assoziiert., 20.7 % of the 2,493 men had erectile dysfunction, 62.9 % were overweight or obese and 57.8 % had a waist-circumference of ≥ 94 cm. With 16.4 %, arterial hypertension was the most common analysed cardiovascular risk factor. Low physical activity (OR: 1.38 / 95 % CI: 1.05-1.81), type 2 diabetes (OR: 2.42 / 95 % CI: 1.34-4.40) and waist-circumference, according to established cut-off values (OR: 1.56 / 95 % CI: 1.26-1.93) and steady in 1 cm steps (OR: 1.03 / 95 % CI: 1.02-1.03), are significantly associated with erectile dysfunction.

Plant-based cheese analogs have emerged as a novel global market trend driven by sustainability concerns for our planet. This study examines eleven soft ripened plant-based cheese analogs produced in Europe, primarily with bloomy rinds and cashew nuts as the main ingredient. First, we focused on exploring the macronutrients and salt content stated on the labels, as well a detailed fatty acid analysis of the samples. Compared to dairy cheeses, plant-based cheeses share similarities in lipid content, but their fatty acid profiles diverge significantly, with higher ratio of mono- and polyunsaturated fatty acids such as oleic and linoleic acids. We also investigated the microbiota of these analog products, employing a culture-dependent and -independent approaches. We identified a variety of microorganisms in the plant-based cheeses, with Lactococcus lactis and Leuconostoc mesenteroides being the dominant bacterial species, and Geotrichum candidum and Penicillium camemberti the dominant fungal species. Most of the species characterized are similar to those present in dairy cheeses, suggesting that they have been inoculated as culture starters to contribute to the sensorial acceptance of plant-based cheeses. However, we also identify several species that are possibly intrinsic to plant matrices or originate from the production environment, such as Pediococcus pentosaceus and Enterococcus spp. This coexistence of typical dairy-associated organisms with plant associated species highlights the potential microbial dynamics inherent in the production of plant-based cheese. These findings will contribute to a better understanding of plant-based cheese alternatives, enable the development of sustainable products, and pave the way for future research exploring the use of plant-based substrates in the production of cheese analogues.

Blue corona discharges are often generated in thunderclouds penetrating into the stratosphere and are the optical manifestation of narrow bipolar events (NBEs) observed in radio signals. While their production appears to depend on convection, the cause and nature of such discharges are not well known. Here we show the observations by a lightning detection array of unusual amounts of 982 NBEs during a tropical storm on the coastline of China. NBEs of negative polarity are predominantly observed at the cloud top reaching the stratosphere, and positive NBEs are primarily at lower altitudes. We find that the dominant polarity changes with the typical time of development of thunderstorm cells, suggesting that the polarity depends on the phase of the storm cells. Furthermore, we find that the lightning jump of negative NBEs is associated with above-anvil cirrus plumes of ice crystals and water vapor in the lower stratosphere. We propose that variations in updrafts induce changes in the altitude and charge concentrations of the cloud layers, which lead to the polarity transition. Our results have implications for studies of the chemical perturbations of greenhouse gas concentrations by corona discharges at the tropopause.

We present an ice-penetrating radar data set acquired over the Greenland ice sheet by aircraft during the years 1971, 1972, 1974, 1978, and 1979. The data set comprises over 177 000 km of flight lines and contains a wealth of information on the state of the Greenland ice sheet, including information on ice thickness and englacial properties. During data collection in the 1970s, the data were recorded on optical film rolls, and in this paper, we document the digitization of these film rolls and their associated geographical information. Our data digitization enables interaction with and analysis of the data and facilitates comparison with modern-day radar observations. The complete data set in full resolution is available in the Stanford Digital Repository (https://doi.org/10.25740/wm135gp2721; Karlsson et al., 2023), with the associated technical reports. Part of the data set is available as low-resolution JPG files at the Technical University of Denmark’s data repository (https://doi.org/10.6084/m9.figshare.c.7235299.v1; Karlsson et al., 2024), with associated technical reports and digitized geographical information . The Stanford Digital Repository serves as long-term storage, providing archival historic preservation in perpetuity, and is not intended as a primary data access point. The Technical University of Denmark (DTU) data repository serves as a primary entry point for data access, with files organized according to acquisition year and flight line in a simple folder structure. Here, we release the full data sets to enable the larger community to access and interact with the data (Karlsson et al., 2023).

Purpose: Nutrition is of paramount importance in critically ill trauma patients. However, adequate supply is difficult to achieve, as caloric requirements are unknown. This study investigated caloric requirements over time, based on indirect calorimetry, in critically ill trauma patients. Methods: Retrospective cohort study at a tertiary trauma center including critically ill trauma patients who underwent indirect calorimetry 2012-2019. Caloric requirements were assessed as resting energy expenditure (REE) during the intensive care unit stay up to 28 days and analyzed in patient-clustered linear regression analysis. Results: A total of 129 patients were included. Median REE per day was 2376 kcal. The caloric intake did not meet REE at any time with a median daily deficit of 1167 kcal. In univariable analysis, ISS was not significantly associated with REE over time (RC 0.03, p = 0.600). Multivariable analysis revealed a significant REE increase (RC 0.62, p < 0.001) and subsequent decrease (RC - 0.03, p < 0.001) over time. Age < 65 years (RC 2.07, p = 0.018), male sex (RC 4.38, p < 0.001), and BMI ≥ 35 kg/m2 (RC 6.94, p < 0.001) were identified as independent predictors for higher REE over time. Severe head trauma was associated with lower REE over time (RC - 2.10, p = 0.030). Conclusion: In critically ill trauma patients, caloric requirements significantly increased and subsequently decreased over time. Younger age, male sex and higher BMI were identified as independent predictors for higher caloric requirements, whereas severe head trauma was associated with lower caloric requirements over time. These results support the use of IC and will help to adjust nutritional support in critically ill trauma patients.

Background: Mounting evidence suggests a significant role of the gut microbiota in the development and progression of colorectal cancer (CRC). In particular, an over-representation of oral pathogens has been linked to CRC. The aim of this study was to further investigate the faecal microbial landscape of CRC patients, with a focus on the oral pathogens Parvimonas micra and Fusobacterium nucleatum. Methods: In this study, 16S rRNA sequencing was conducted using faecal samples from CRC patients (n = 275) and controls without pathological findings (n = 95). Results: We discovered a significant difference in microbial composition depending on tumour location and microsatellite instability (MSI) status, with P. micra, F. nucleatum, and Peptostreptococcus stomatis found to be more abundant in patients with MSI tumours. Moreover, P. micra and F. nucleatum were associated with a cluster of CRC-related bacteria including Bacteroides fragilis as well as with other oral pathogens such as P. stomatis and various Porphyromonas species. This cluster was distinctly different in the control group, suggesting its potential linkage with CRC. Conclusions: Our results suggest a similar distribution of several CRC-associated bacteria within CRC patients, underscoring the importance of considering the concomitant presence of bacterial species in studies investigating the mechanisms of CRC development and progression.

An advection-diffusion model coupled to a simple dynamical ocean model is used to illustrate the formation and ventilation of an oxygen minimum zone. The advection-diffusion model carries a tracer mimicking oxygen, and the dynamical model is a non-linear 1 ½ layer reduced-gravity model. The latter is forced by an annually oscillating mass flux confined to the near-equatorial band that, in turn, leads to the generation of mesoscale eddies and latitudinally alternating zonal jets at higher latitudes. The model uses North Atlantic geometry and develops a tracer minimum zone remarkably similar in location to the observed oxygen minimum zone in the Eastern Tropical North Atlantic (ETNA). This is despite the absence of wind forcing and the shadow zone predicted by the ventilated thermocline theory. Although the model is forced only at the annual period, the model nevertheless exhibits decadal and multidecadal variability in its spun-up state. The associated trends are comparable to observed trends in oxygen within the ETNA oxygen minimum zone. Notable exceptions are the multi-decadal decrease in oxygen in the lower oxygen minimum zone, and the sharp decrease in oxygen in the upper oxygen minimum zone between 2006 and 2013.

The interaction of perfluorinated molecules, also known as “forever chemicals” due to their pervasiveness, with their environment remains an important yet poorly understood topic. In this work, the self-assembly of perfluorinated molecules with multivalent hosts, pillar-[5]-arenes, is investigated. It is found that perfluoroalkyl diacids and pillar-[5]-arenes rapidly and strongly complex with each other at aqueous interfaces, forming solid interfacially templated films. Their complexation is shown to be driven primarily by fluorophilic aggregation and assisted by electrostatic interactions, as supported by the crystal structure of the complexes, and leads to the formation of quasi-2D phase-separated films. This self-assembly process can be further manipulated using aqueous two-phase system microdroplets, enabling the controlled formation of 3D micro-scaffolds.

Per- and polyfluoroalkyl substances (PFAS) pose a rapidly increasing global problem as their widespread use and high stability lead worldwide to water contamination, with significant detrimental health effects.[1] Supramolecular chemistry has been invoked to develop materials geared towards the specific capture of PFAS from water,[2] to reduce the concentration below advisory safety limits (e.g., 70 ng/L for the sum of perfluorooctane sulfonic acid, PFOS and perfluorooctanoic acid, PFOA). Scale-up and use in natural waters with high PFAS concentrations has hitherto posed a problem. Here we report a new type of host–guest interaction between deca-ammonium-functionalized pillar[5]arenes (DAF−P5s) and perfluoroalkyl acids. DAF−P5 complexes show an unprecedented 1 : 10 stoichiometry, as confirmed by isothermal calorimetry and X-ray crystallographic studies, and high binding constants (up to 106 M−1) to various polyfluoroalkyl acids. In addition, non-fluorinated acids do not hamper this process significantly. Immobilization of DAF−P5s allows a simple single-time filtration of PFAS-contaminated water to reduce the PFOS/PFOA concentration 106 times to 15–50 ng/L level. The effective and fast (<5 min) orthogonal binding to organic molecules without involvement of fluorinated supramolecular hosts, high breakthrough capacity (90 mg/g), and robust performance (>10 regeneration cycles without decrease in performance) set a new benchmark in PFAS-absorbing materials.

An advection-diffusion model coupled to a simple dynamical ocean model is used to illustrate the formation and ventilation of an oxygen minimum zone. The advection-diffusion model carries a tracer mimicking oxygen, and the dynamical model is a non-linear 1 ½ layer reduced-gravity model. The latter is forced by an annually oscillating mass flux confined to the near-equatorial band that, in turn, leads to the generation of mesoscale eddies and latitudinally alternating zonal jets at higher latitudes. The model uses North Atlantic geometry and develops a tracer minimum zone remarkably similar in location to the observed oxygen minimum zone in the Eastern Tropical North Atlantic (ETNA). This is despite the absence of wind forcing and the shadow zone predicted by the ventilated thermocline theory. Although the model is forced only at the annual period, the model nevertheless exhibits decadal and multidecadal variability in its spun-up state. The associated trends are comparable to observed trends in oxygen within the ETNA oxygen minimum zone. Notable exceptions are the multi-decadal decrease in oxygen in the lower oxygen minimum zone, and the sharp decrease in oxygen in the upper oxygen minimum zone between 2006 and 2013.

An advection-diffusion model coupled to a simple dynamical ocean model is used to illustrate the formation and ventilation of an oxygen minimum zone. The advection-diffusion model carries a tracer mimicking oxygen, and the dynamical model is a non-linear 1 ½ layer reduced-gravity model. The latter is forced by an annually oscillating mass flux confined to the near-equatorial band that, in turn, leads to the generation of mesoscale eddies and latitudinally alternating zonal jets at higher latitudes. The model uses North Atlantic geometry and develops a tracer minimum zone remarkably similar in location to the observed oxygen minimum zone in the Eastern Tropical North Atlantic (ETNA). This is despite the absence of wind forcing and the shadow zone predicted by the ventilated thermocline theory. Although the model is forced only at the annual period, the model nevertheless exhibits decadal and multidecadal variability in its spun-up state. The associated trends are comparable to observed trends in oxygen within the ETNA oxygen minimum zone. Notable exceptions are the multi-decadal decrease in oxygen in the lower oxygen minimum zone, and the sharp decrease in oxygen in the upper oxygen minimum zone between 2006 and 2013.

Background: Processing information from massively parallel sequencing/next-generation sequencing (NGS) data involves several steps that transform millions of rows of input data into more accessible genetic information. The combination of bioinformatics tools that extract all requested information for a particular clinical/research application, how they are tuned and the order in which they are executed constitute a bioinformatics pipeline. Software is often reused in several pipelines and regularly updated. For clinically validated NGS pipelines it may be challenging when individual components of several pipelines needs updating or when tools are replaced with new applications. Methods: The Hydra-genetics framework takes advantage of version controlled Snakemake modules. Pipeline steps are split into modules that can be configured and tested individually. The modules can be combined to build complete bioinformatics analyses, or be added to existing pipelines. All modules are subjected to extensive testing to ensure that new releases do not unexpectedly break existing pipelines or deviate from guidelines and best practices on how to write code. Results: Bioinformaticians from five Genomics Medicine Sweden centers used Hydra-genetics to develop the bioinformatics pipeline for the comprehensive solid tumor panel, GMS560. The pipeline analyses tumor DNA and/or RNA data and generates information on genetic variation including complex biomarkers such as tumor mutation burden and microsatellite instability. It is validated and in clinical use. Conclusions: The Hydra-genetics framework provides a platform for structured bioinformatics pipeline development and facilitates joint development projects involving multiple partners. It makes clinical pipeline development easier, faster and more structured.

STI sind ein weltweites Gesundheitsproblem. Die STI-Lebenszeitprävalenz lag bei den 468 befragten Studierenden (Durchschnittsalter 24,9 Jahre) bei 15,6% (Studentinnen: 14,7%, Studenten: 17,1%). Die häufigsten STI waren Chlamydien und HPV. Mit STI assoziierte Parameter der Studentinnen waren: insges. ≥10 Sexualpartner*innen, Alter >25 Jahre, One-Night-Stand in der Vorgeschichte. Mit STI assoziierte Parameter der Studenten waren: insges. ≥10 Sexualpartner*innen, Männer als sexuell bevorzugtes Geschlecht, jemals Geschlechtsverkehr mit mehr als einer Person zur selben Zeit., STIs remain a global health problem. Lifetime STI prevalence among the 468 students surveyed (mean age 24.9 years) was 15.6% (female: 14.7%, male: 17.1%). The most frequent STIs were chlamydia and HPV. Parameters associated with STIs in female students were: total ≥10 sexual partners, age >25, history of one-night stand. Parameters associated with STIs in male students were: total ≥10 sexual partners, men as sexually preferred gender, ever having sexual intercourse with more than one person at the same time.

Terrestrial gamma-ray flashes (TGFs) are bursts of energetic X- and gamma-rays emitted from thunderstorms. The Atmosphere-Space Interactions Monitor (ASIM) mounted onto the International Space Station (ISS) is dedicated to measure TGFs and optical signatures of lightning; ISS LIS (Lightning Imaging Sensor) detects lightning flashes allowing for simultaneous measurements with ASIM. Whilst ASIM measures ∼300-400 TGFs per year, ISS LIS detects ∼106 annual lightning flashes giving a disproportion of four orders of magnitude. Based on the temporal evolution of lightning flashes and the spatial pattern of the constituing events, we present an algorithm to reduce the number of space-detected flashes potentially associated with TGFs by ∼ 60% and of associated LIS groups by ∼ 95%. We use ASIM measurements to confirm that the resulting flashes are indeed those associated with TGFs detected at approx. 400 km altitude and thus benchmark our algorithm preserving 70–80% of TGFs from concurrent ASIM-LIS measurements. We compare how the radiance, footprint size and the global distribution of lightning flashes of the reduced set relates to the average of all measured lightning flashes and do not observe any significant difference. Finally, we present a parameter study of our algorithm and discuss which parameters can be tweaked to maximize the reduction efficiency whilst keeping flashes associated to TGFs. In the future, this algorithm will hence be capable of facilitating the search for TGFs in a reduced set of lightning flashes measured from space.

The ACL Anthology is a prime resource for research papers within computational linguistics and natural language processing, while continuing to be an open-source and community-driven project. Since Gildea et al. (2018) reported on its state and planned directions, the Anthology has seen major technical changes. We discuss what led to these changes and how they impact long-term maintainability and community engagement, describe which open-source data and software tools the Anthology currently provides, and provide a survey of literature that has used the Anthology as a main data source.

In January 2019, a new leasing standard called IFRS 16 was implemented because of the criticism received by the previous leasing standard, IAS 17. The main criticism of the previous standard was that significant assets were not being correctly reported on the balance sheet. The new standard requires that previous operating leases are now reported as a right-of-use asset and a lease liability on the balance sheet. IFRS 16 has resulted in a change to the financial position of companies, with the retail sector expected to see significant changes in key financial ratios. The purpose of the study was to increase understanding of the effects the new standard has on the risks and profitability of the retail sector. The study collected data from 44 companies operating in Scandinavia and key financial ratios were examined. Three comparison groups were selected to increase understanding of the differences between the various sectors. The Scandinavian retail sector's ROA, ROE, solidity, and leverage ratios showed significant changes after the implementation of IFRS 16. The financial risk, operating risk and profitability of the Scandinavian retail sector were indirectly affected as these are measured using the key financial ratios used in the study. The analysis model used in the study showed differences between the comparison groups, with the retail and air transport sectors having the greatest impact of the new standard. The study's conclusion is that the risks and profitability of the Scandinavian retail sector have changed after the implementation of IFRS 16, as the selected key financial ratios showed significant changes., I januari 2019 beslutades det att en ny leasingstandard vid namn IFRS 16 skulle implementeras som en följd av den kritik den tidigare leasingstandarden IAS 17 fått motstå. Kritiken mot den tidigare standarden var till stor del att väsentliga tillgångar inte redovisades korrekt i balansräkningen. Den nya standarden innebär att de tidigare operationella leasingavtalen nu ska redovisas som en nyttjanderättstillgång och en leasingskuld i balansräkningen. IFRS 16 innebär att företagens finansiella ställningen förändras, där detaljhandeln är en av de sektorerna som förväntas få störst förändringar i nyckeltalen. Syftet med studien är att beskriva hur implemeteringen av IFRS 16 har påverkat den skandinaviska detaljhandelns risker och lönsamhet. Studien har genomförts med hjälp av datainsamling från 44 bolag verksamma inom Skandinavien och väsentliga nyckeltal har undersökts. Tre jämförelsesektorer valdes ut för att skapa en ökad förståelse i skillnaderna mellan de olika sektorerna. Den skandinaviska detaljhandelns ROA, ROE, Soliditet och skuldsättningsgrad visade väsentliga förändringar efter implementeringen av IFRS 16. Den finansiella risken, rörelserisken och lönsamheten för den skandinaviska detaljhandeln fick indirekt en påverkan eftersom dessa mäts med hjälp av de använda nyckeltalen. Analysmodellen som studien använde sig av visade skillnader mellan jämförelsesektorer där detaljhandeln samt flygtransport har påverkats mest av implementeringen av den nya standarden. Studiens slutsats är att den skandinaviska detaljhandelns risker och lönsamhet, har förändrats efter implementeringen av IFRS 16 eftersom de utvalda nyckeltalen visade på signifikanta förändringar.

In this work we present a comprehensive account of our current knowledge on vascular morphogenesis, both from a biological and a mathematical point of view. To this end, we first describe the basic steps in the known mechanisms of blood vessel morphogenesis, whose structure, function and unfolding properties are examined. We then provide a wide, although by no means exhaustive, account of mathematical models which are used to describe and discuss particular aspects of the overall biological process considered. We finally summarize the approaches presented, and suggest possible directions for future research. Details about some of the major signalling molecules involved are included in a first Appendix at the end of the paper. A second Appendix provides a brief overview of design principles for vascular nets, a subject that has deserved considerable attention over the years., Banco Santander Central Hispano, Universidad Complutense de Madrid, Ministerio de Ciencia e Innovacion, Spain, European Community's Sixth Framework Programme contract ("HeartRepair"), ISCIII cooperative and thematic research networks RECAVA and TERCEL, Depto. de Análisis Matemático y Matemática Aplicada, Fac. de Ciencias Matemáticas, TRUE, pub

Blue corona discharges are often observed at the top of thunderclouds. They are bursts of streamers, but the cloud conditions that enable them are not well known. Here we present observations by the Atmosphere‐Space Interactions Monitor (ASIM) of 92 discharges during its ∼1 min pass over tropical cyclone Fani in the Bay of Bengal from 20:10:55 to 20:12:05 UTC on 30 April 2019. The discharges were observed in convective cells forming in the rainbands of the cyclone where Convective Available Potential Energy reached ∼6,000 J kg−1. The Cloud‐Aerosol Lidar and Infrared Pathfinder Satellite Observation satellite passed over one of the cells ∼12 min after ASIM from 20:23:58 to 20:24:14 UTC. It measured the cloud microphysics related to the discharges and indicated they occurred in a convection region with the cloud top overshooting for over 20 min. The updraft lifted ice particles to lower stratospheric altitudes and formed the gullwing‐shaped cirrus. The discharges are found at an average altitude of ∼16 km where the cloud environment contained ∼2 × 107 m−3 ice particles with ∼50 µm radius, resulting in a photon mean free path of ∼3 m. Around 20% of the blue corona discharges coincide with Narrow Bipolar Events indentified from the Earth Networks Total Lightning Network. Our observations suggest that the overshooting cloud top formed by deep convection and a surge in lightning activity facilitated conditions for the blue corona discharges. This work provides the first‐ever estimate of important microphysical parameters related to blue corona discharges based on data measurements, establishing a reference for future empirical and theoretical studies.

Current approaches to staging chronic liver diseases have limited utility for predicting liver cancer risk. Here, we employed single-nucleus RNA sequencing (snRNA-seq) to characterize the cellular microenvironment of healthy and pre-malignant livers using two distinct mouse models. Downstream analyses unraveled a previously uncharacterized disease-associated hepatocyte (daHep) transcriptional state. These cells were absent in healthy livers but increasingly prevalent as chronic liver disease progressed. Copy number variation (CNV) analysis of microdissected tissue demonstrated that daHep-enriched regions are riddled with structural variants, suggesting these cells represent a pre-malignant intermediary. Integrated analysis of three recent human snRNA-seq datasets confirmed the presence of a similar phenotype in human chronic liver disease and further supported its enhanced mutational burden. Importantly, we show that high daHep levels precede carcinogenesis and predict a higher risk of hepatocellular carcinoma development. These findings may change the way chronic liver disease patients are staged, surveilled, and risk stratified.

Electromagnetic pulses (EMPs) and quasi‐static electric fields (QE) from powerful lightning heat and ionize the lower ionosphere. The EMP disturbance may appear as an elve at ∼80–95 km altitude, and the QE field as a halo or a sprite at ∼60–80 km altitude. Both are thought to perturb crossing radio signals because of changes to the electrical conductivity of the regions. Here we present an analysis of 63 elves and corresponding radio signal perturbations from an almost stationary thunderstorm system that allows us to untangle some of the dependencies of perturbations on the lightning characteristics. The amplitude perturbations of a VLF‐transmitter signal are characterized as either long‐recovery, early events (LOREs) or as early events. We find that LOREs are related to lightning with high peak currents and bright elves, and that their sign (amplitude increase or decrease) depends on the relative locations of the transmitter, disturbance and receiver. Based on a subset of strokes, lightning with elves has on average ∼3 times the impulse charge‐moment‐change and power in broadband as lightning of similar peak currents without elves. The early events occur without observed elves, sprites or halos. They recover in ∼10–100 s and are observed for both polarities of cloud‐to‐ground lightning and for intracloud flashes. It is proposed that these observations may relate to regions of reduced conductivity caused by an electron attachment/detachment process at lower heights, or by electron enhancements associated with TLEs that are too dim to be detected by the camera.

The nucleation of sulfuric acid–water clusters is a significant contribution to the formation of aerosols as precursors of cloud condensation nuclei (CCN). Depending on the temperature, there is an interplay between the clustering of particles and their evaporation controlling the efficiency of cluster growth. For typical temperatures in the atmosphere, the evaporation of (Formula presented.) clusters is more efficient than the clustering of the first, small clusters, and thus their growth is dampened at its early stages. Since the evaporation rates of small clusters containing an (Formula presented.) ion are much smaller than for purely neutral sulfuric acid clusters, they can serve as a central body for the further attachment of (Formula presented.) molecules. We here present an innovative Monte Carlo model to study the growth of aqueous sulfuric acid clusters around central ions. Unlike classical thermodynamic nucleation theory or kinetic models, this model allows to trace individual particles and thus to determine properties for each individual particle. As a benchmarking case, we have performed simulations at (Formula presented.) a relative humidity of 50% with dipole and ion concentrations of (Formula presented.) and (Formula presented.). We discuss the runtime of our simulations and present the velocity distribution of ionic clusters, the size distribution of the clusters as well as the formation rate of clusters with radii (Formula presented.). Simulations give reasonable velocity and size distributions and there is a good agreement of the formation rates with previous results, including the relevance of ions for the initial growth of sulfuric acid–water clusters. Conclusively, we present a computational method which allows studying detailed particle properties during the growth of aerosols as a precursor of CCN.

Studien deuten darauf hin, dass der Einsatz von Tablets das Interesse von Lernenden am Unterricht wecken kann. Offen bleibt darin die Frage, ob die international unterschiedlichen curricularen Vorgaben zur Förderung von Medienkompetenz durch digitale Medien (im Rahmen der regulären Unterrichtszeit vs. im Rahmen zusätzlicher Unterrichtszeit durch ein zusätzliches Unterrichtsfach) das Interesse am Unterricht beeinflussen. Zur Beantwortung dieser Frage wurde eine Gruppe mit Tableteinsatz im Rahmen der regulären Unterrichtszeit (n = 20) und eine Gruppe mit Tableteinsatz einschliesslich zusätzlicher Unterrichtszeit, um den Umgang mit dem Tablet zu erlernen (n = 27), einer ohne Tablets unterrichteten Kontrollgruppe von Viertklässler:innen (n = 31) gegenübergestellt. Die Ergebnisse deuten auf Unterschiede zwischen den Gruppen hinsichtlich des Interesses am durchgeführten Unterricht hin, wobei die Gruppe mit zusätzlicher Unterrichtszeit der anderen Tablet-Gruppe überlegen ist. Dies deutet darauf hin, dass beim Einsatz von Tablets im Fachunterricht zusätzliche Unterrichtszeit förderlich für das situationale Interesse ist. Die Ergebnisse werden vor dem Hintergrund der Selbstbestimmungstheorie diskutiert und Limitationen der Untersuchung aufgezeigt., Existing studies indicate that the use of tablets is suitable for stimulating learnersʼ interest in the classroom. Up to now, it remains an open question as to whether the internationally differing curricular requirements for promoting media competence through digital media (within regular lesson time vs. with additional lesson time in terms of a particular subject) influence the pupilsʼ interest in the lesson. To answer this question, a group that used tablets in primary science during regular lesson time (n = 20) and a group that used tablets in primary science and additional lesson time to learn how to use the tablets (n = 27) were compared with a control group of fourth graders (n = 31) taught without tablets. The results indicate differences between the groups in interest depending on the instruction provided, with the group with additional lesson time being superior to the other tablet group. This suggests that additional lesson time may be conducive to situational interest when using tablets in subject lessons at primary level. Finally, we discuss the results against the background of the self-determination theory and point out the limitations of the study.

Alternative community-based data distribution networks on the local scale have emerged in Cuba as a consequence of the economic sanctions imposed on the country in recent decades. German anthropologist Steffen Köhn and Cuban media artist Nestor Siré shed light on the unique materiality and significance of these networks, built to overcome the limitations of internet access in Cuba. In the current capitalist, consumerist form of internet, characterised by closed platforms, we are fed content chosen for us by algorithms, whereas informal infrastructures allow their users, makers and content creators to be the protagonists of their own choices – and allow us to envision decentralised, non-commercial and collective interactions on the web., https://www.librarystack.org/scale-alternative-networks-in-cuba/?ref=unknown

In January 2019, a new leasing standard called IFRS 16 was implemented because of the criticism received by the previous leasing standard, IAS 17. The main criticism of the previous standard was that significant assets were not being correctly reported on the balance sheet. The new standard requires that previous operating leases are now reported as a right-of-use asset and a lease liability on the balance sheet. IFRS 16 has resulted in a change to the financial position of companies, with the retail sector expected to see significant changes in key financial ratios. The purpose of the study was to increase understanding of the effects the new standard has on the risks and profitability of the retail sector. The study collected data from 44 companies operating in Scandinavia and key financial ratios were examined. Three comparison groups were selected to increase understanding of the differences between the various sectors. The Scandinavian retail sector's ROA, ROE, solidity, and leverage ratios showed significant changes after the implementation of IFRS 16. The financial risk, operating risk and profitability of the Scandinavian retail sector were indirectly affected as these are measured using the key financial ratios used in the study. The analysis model used in the study showed differences between the comparison groups, with the retail and air transport sectors having the greatest impact of the new standard. The study's conclusion is that the risks and profitability of the Scandinavian retail sector have changed after the implementation of IFRS 16, as the selected key financial ratios showed significant changes., I januari 2019 beslutades det att en ny leasingstandard vid namn IFRS 16 skulle implementeras som en följd av den kritik den tidigare leasingstandarden IAS 17 fått motstå. Kritiken mot den tidigare standarden var till stor del att väsentliga tillgångar inte redovisades korrekt i balansräkningen. Den nya standarden innebär att de tidigare operationella leasingavtalen nu ska redovisas som en nyttjanderättstillgång och en leasingskuld i balansräkningen. IFRS 16 innebär att företagens finansiella ställningen förändras, där detaljhandeln är en av de sektorerna som förväntas få störst förändringar i nyckeltalen. Syftet med studien är att beskriva hur implemeteringen av IFRS 16 har påverkat den skandinaviska detaljhandelns risker och lönsamhet. Studien har genomförts med hjälp av datainsamling från 44 bolag verksamma inom Skandinavien och väsentliga nyckeltal har undersökts. Tre jämförelsesektorer valdes ut för att skapa en ökad förståelse i skillnaderna mellan de olika sektorerna. Den skandinaviska detaljhandelns ROA, ROE, Soliditet och skuldsättningsgrad visade väsentliga förändringar efter implementeringen av IFRS 16. Den finansiella risken, rörelserisken och lönsamheten för den skandinaviska detaljhandeln fick indirekt en påverkan eftersom dessa mäts med hjälp av de använda nyckeltalen. Analysmodellen som studien använde sig av visade skillnader mellan jämförelsesektorer där detaljhandeln samt flygtransport har påverkats mest av implementeringen av den nya standarden. Studiens slutsats är att den skandinaviska detaljhandelns risker och lönsamhet, har förändrats efter implementeringen av IFRS 16 eftersom de utvalda nyckeltalen visade på signifikanta förändringar.

Chronic pancreatitis increases the risk of developing pancreatic cancer through the upregulation of pathways favouring proliferation, fibrosis, and sustained inflammation. We established in previous studies that the ligand tumour necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) signals through its cognate receptor fibroblast growth factor-inducible 14 (Fn14) to regulate these underlying cellular processes in the chronic liver injury niche. However, the role of the TWEAK/Fn14 signalling pathway in pancreatic disease is entirely unknown. An analysis of publicly available datasets demonstrated that the TWEAK receptor Fn14 is upregulated in pancreatitis and pancreatic adenocarcinoma, with single cell RNA sequencing revealing pancreatic ductal cells as the main Fn14 producers. We then used choline-deficient, ethionine-supplemented (CDE) diet feeding of wildtype C57BL/6J and Fn14 knockout littermates to (a) confirm CDE treatment as a suitable model of chronic pancreatitis and (b) to investigate the role of the TWEAK/Fn14 signalling pathway in pancreatic ductal proliferation, as well as fibrotic and inflammatory cell dynamics. Our time course data obtained at three days, three months, and six months of CDE treatment reveal that a lack of TWEAK/Fn14 signalling significantly inhibits the establishment and progression of the tissue microenvironment in CDE-induced chronic pancreatitis, thus proposing the TWEAK/Fn14 pathway as a novel therapeutic target.

We have investigated how kinetic instabilities such as the Weibel instability (WI), the mushroom instability (MI), and the kinetic Kelvin–Helmholtz instability (kKHI) are excited in jets without and with a toroidal magnetic field, and how such instabilities contribute to particle acceleration. In this work, we use a new jet injection scheme, where an electric current is self-consistently generated at the jet orifice by the jet particles, which produce the toroidal magnetic field. We perform five different simulations for a sufficiently long time to examine the non-linear effects of the jet evolution. We inject unmagnetized e± and e−– p+ (mp/me = 1836), as well as magnetized e± and e−– i+ (mi/me = 4) jets with a top-hat jet density profile into an unmagnetized ambient plasmas of the same species. We show that WI, MI, and kKHI excited at the linear stage, generate a non-oscillatory x-component of the electric field accelerating, and decelerating electrons. We find that the two different jet compositions (e± and e−– i+) display different instability modes, respectively. Moreover, the magnetic field in the non-linear stage generated by different instabilities is dissipated and reorganized into new topologies. A 3D magnetic field topology depiction indicates possible reconnection sites in the non-linear stage, where the particles are significantly accelerated by the dissipation of the magnetic field associated to a possible reconnection event. © 2022 The Author(s) Published by Oxford University Press on behalf of Royal Astronomical Society.

We have investigated how kinetic instabilities such as the Weibel instability (WI), the mushroom instability (MI), and the kinetic Kelvin–Helmholtz instability (kKHI) are excited in jets without and with a toroidal magnetic field, and how such instabilities contribute to particle acceleration. In this work, we use a new jet injection scheme, where an electric current is self-consistently generated at the jet orifice by the jet particles, which produce the toroidal magnetic field. We perform five different simulations for a sufficiently long time to examine the non-linear effects of the jet evolution. We inject unmagnetized e± and e−– p+ (mp/me = 1836), as well as magnetized e± and e−– i+ (mi/me = 4) jets with a top-hat jet density profile into an unmagnetized ambient plasmas of the same species. We show that WI, MI, and kKHI excited at the linear stage, generate a non-oscillatory x-component of the electric field accelerating, and decelerating electrons. We find that the two different jet compositions (e± and e−– i+) display different instability modes, respectively. Moreover, the magnetic field in the non-linear stage generated by different instabilities is dissipated and reorganized into new topologies. A 3D magnetic field topology depiction indicates possible reconnection sites in the non-linear stage, where the particles are significantly accelerated by the dissipation of the magnetic field associated to a possible reconnection event.

Blue corona discharges are often observed at the top of thunderclouds. They are bursts of streamers, but the cloud conditions that enable them are not well known. Here we present observations by the Atmosphere-Space Interactions Monitor (ASIM) of 92 discharges during its ∼1 min pass over tropical cyclone Fani in the Bay of Bengal from 20:10:55 to 20:12:05 UTC on 30 April 2019. The discharges were observed in convective cells forming in the rainbands of the cyclone where Convective Available Potential Energy reached ∼6,000 J kg. The Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observation satellite passed over one of the cells ∼12 min after ASIM from 20:23:58 to 20:24:14 UTC. It measured the cloud microphysics related to the discharges and indicated they occurred in a convection region with the cloud top overshooting for over 20 min. The updraft lifted ice particles to lower stratospheric altitudes and formed the gullwing-shaped cirrus. The discharges are found at an average altitude of ∼16 km where the cloud environment contained ∼2 × 10 m ice particles with ∼50 µm radius, resulting in a photon mean free path of ∼3 m. Around 20% of the blue corona discharges coincide with Narrow Bipolar Events indentified from the Earth Networks Total Lightning Network. Our observations suggest that the overshooting cloud top formed by deep convection and a surge in lightning activity facilitated conditions for the blue corona discharges. This work provides the first-ever estimate of important microphysical parameters related to blue corona discharges based on data measurements, establishing a reference for future empirical and theoretical studies. © 2023. The Authors.

Particle-in-Cell simulations can provide a possible answer to an important key issue for astrophysical plasma jets; namely on how a toroidal magnetic field affects the evolution of pair and electron-ion jets. We show that Weibel, mushroom, and kinetic Kelvin-Helmhotz instabilities excited at the linear stage, generate a quasi-steady x-component of the electric field which accelerates and decelerates electrons. We observe significant differences in the structure of the strong electromagnetic fields that are driven by the kinetic instabilities with the pair jet. We find that the two different jet compositions (e± and e- - i+) generate different instability modes respectively. Moreover, the magnetic field in the non-linear stage generated by different instabilities is dissipated and reorganized into new topologies. A 3D magnetic field topology depiction indicates possible reconnection sites in the non-linear stage where the particles are significantly accelerated by the dissipation of the magnetic field associated to a possible reconnection manifestation. © The Author(s), 2023. Published by Cambridge University Press on behalf of International Astronomical Union

In einer Langzeitstudie wurde untersucht, wie es älteren Menschen, die aufgrund eines akuten Ereignisses eine rehabilitative Übergangspflege in den Gesundheitszentren für das Alter der Stadt Zürich benötigten, vor und nach dem Aufenthalt ergangen ist. Im Mittelpunkt steht das Krisenerleben der Patienten und wie sie und ihre Angehörigen zuhause zurechtkommen. Im Workshop werden die Studienergebnisse vorgestellt und die Konsequenzen für die Pflegepraxis gemeinsam mit den Teilnehmenden diskutiert.

Root phenology influences the timing of plant resource acquisition and carbon fluxes into the soil. This is particularly important in fen peatlands, in which peat is primarily formed by roots and rhizomes of vascular plants. However, most fens in Central Europe are drained for agriculture, leading to large carbon losses, and further threatened by increasing frequency and intensity of droughts. Rewetting fens aims to restore the original carbon sink, but how root phenology is affected by drainage and rewetting is largely unknown. We monitored root phenology with minirhizotrons in drained and rewetted fens (alder forest, percolation fen and coastal fen) as well as its soil temperature and water table depth during the 2018 drought. For each fen type, we studied a drained site and a site that was rewetted ~25 years ago, while all the sites studied had been drained for almost a century. Overall, the growing season was longer with rewetting, allowing roots to grow over a longer period in the year and have a higher root production than under drainage. With increasing depth, the growing season shifted to later in time but remained a similar length, and the relative importance of soil temperature for root length changes increased with soil depth. Synthesis and applications: Rewetting extended the growing season of roots, highlighting the importance of phenology in explaining root productivity in peatlands. A longer growing season allows a longer period of carbon sequestration in form of root biomass and promotes the peatlands' carbon sink function, especially through longer growth in deep soil layers. Thus, management practices that focus on rewetting peatland ecosystems are necessary to maintain their function as carbon sinks, particularly under drought conditions, and are a top priority to reduce carbon emissions and address climate change.

To improve treatment of metastatic prostate cancer, the biology of metastases needs to be understood. We recently described three subtypes of prostate cancer bone metastases (MetA-C), based on differential gene expression. The aim of this study was to verify the clinical relevance of these subtypes and to explore their biology and relations to genetic drivers. Freshly-frozen metastasis samples were obtained as hormone-naive (n = 17), short-term castrated (n = 21), or castration-resistant (n = 65) from a total of 67 patients. Previously published sequencing data from 573 metastasis samples were also analyzed. Through transcriptome profiling and sample classification based on a set of predefined MetA-C-differentiating genes, we found that most metastases were heterogeneous for the MetA-C subtypes. Overall, MetA was the most common subtype, while MetB was significantly enriched in castration-resistant samples and in liver metastases, and consistently associated with poor prognosis. By gene set enrichment analysis, the phenotype of MetA was described by high androgen response, protein secretion and adipogenesis, MetB by high cell cycle activity and DNA repair, and MetC by epithelial-to-mesenchymal transition and inflammation. The MetB subtype demonstrated single nucleotide variants of RB transcriptional corepressor 1 (RB1) and loss of 21 genes at chromosome 13, including RB1, but provided independent prognostic value to those genetic aberrations. In conclusion, a distinct set of gene transcripts can be used to classify prostate cancer metastases into the subtypes MetA-C. The MetA-C subtypes show diverse biology, organ tropism, and prognosis. The MetA-C classification may be used independently, or in combination with genetic markers, primarily to identify MetB patients in need of complementary therapy to conventional androgen receptor-targeting treatments.

Root phenology influences the timing of plant resource acquisition and carbon fluxes into the soil. This is particularly important in fen peatlands, in which peat is primarily formed by roots and rhizomes of vascular plants. However, most fens in Central Europe are drained for agriculture, leading to large carbon losses, and further threatened by increasing frequency and intensity of droughts. Rewetting fens aims to restore the original carbon sink, but how root phenology is affected by drainage and rewetting is largely unknown. We monitored root phenology with minirhizotrons in drained and rewetted fens (alder forest, percolation fen and coastal fen) as well as its soil temperature and water table depth during the 2018 drought. For each fen type, we studied a drained site and a site that was rewetted ~25 years ago, while all the sites studied had been drained for almost a century. Overall, the growing season was longer with rewetting, allowing roots to grow over a longer period in the year and have a higher root production than under drainage. With increasing depth, the growing season shifted to later in time but remained a similar length, and the relative importance of soil temperature for root length changes increased with soil depth. Synthesis and applications: Rewetting extended the growing season of roots, highlighting the importance of phenology in explaining root productivity in peatlands. A longer growing season allows a longer period of carbon sequestration in form of root biomass and promotes the peatlands' carbon sink function, especially through longer growth in deep soil layers. Thus, management practices that focus on rewetting peatland ecosystems are necessary to maintain their function as carbon sinks, particularly under drought conditions, and are a top priority to reduce carbon emissions and address climate change.

To improve treatment of metastatic prostate cancer, the biology of metastases needs to be understood. We recently described three subtypes of prostate cancer bone metastases (MetA-C), based on differential gene expression. The aim of this study was to verify the clinical relevance of these subtypes and to explore their biology and relations to genetic drivers. Freshly-frozen metastasis samples were obtained as hormone-naive (n = 17), short-term castrated (n = 21), or castration-resistant (n = 65) from a total of 67 patients. Previously published sequencing data from 573 metastasis samples were also analyzed. Through transcriptome profiling and sample classification based on a set of predefined MetA-C-differentiating genes, we found that most metastases were heterogeneous for the MetA-C subtypes. Overall, MetA was the most common subtype, while MetB was significantly enriched in castration-resistant samples and in liver metastases, and consistently associated with poor prognosis. By gene set enrichment analysis, the phenotype of MetA was described by high androgen response, protein secretion and adipogenesis, MetB by high cell cycle activity and DNA repair, and MetC by epithelial-to-mesenchymal transition and inflammation. The MetB subtype demonstrated single nucleotide variants of RB transcriptional corepressor 1 (RB1) and loss of 21 genes at chromosome 13, including RB1, but provided independent prognostic value to those genetic aberrations. In conclusion, a distinct set of gene transcripts can be used to classify prostate cancer metastases into the subtypes MetA-C. The MetA-C subtypes show diverse biology, organ tropism, and prognosis. The MetA-C classification may be used independently, or in combination with genetic markers, primarily to identify MetB patients in need of complementary therapy to conventional androgen receptor-targeting treatments.

År 2003 gjordes en nationell utvärdering av Skolverket över hem- och konsumentkunskaps ämnets måluppfyllelse. Syftet med studien 2022 var att undersöka elevers syn på ämnet hem- och konsumentkunskap och om detta förändrats sedan Skolverkets senaste utvärderingen av ämnet 2003. Metoden för undersökningen gjordes genom förfrågan till olika grupper på Facebook, för ämneslärare i hem- och konsumentkunskap. Ämneslärare (Hkk) delade enkäten med årskurs 9:e elever och enkäten besvarades av 153 elev – respondenter i studien 2022. Data sammanställdes i Microsoft Excell och analyserades digitalt och manuellt. Studien 2022 visade att elevernas syn på Hkk- ämnets betydelse har minskat för livet i hem och familj i jämförelse mot Skolverkets utvärdering 2003. Dessutom visar resultatet 2022 även på att eleverna i låg omfattning upplever att de har möjlighet att påverka både undervisningen och känna delaktighet, vilket är lägre än Skolverkets utvärdering 2003. Den viktigaste slutsatsen utifrån denna studie 2022 är att ämneslärare i Hkk bör tydligare synliggöra nyttan med ämnet för elevens framtid och genom det öka motivationen för elevens lärande.

Procedural Content Generation (PCG) in games often suffers from a lack of emotional connection with the player as well as a perceived sameness. This thesis aims to design and test a tool for PCG game levels for the game To the Skies! which incorporates an emotional intention based upon the color-emotion theory proposed by Fugate and Franco, 2019. Russell’s (1980) Circumplex Model of Affect was used as a foundation for the parameterization of emotions, which were implemented in a PCG test level for the game, developed in Unreal Engine. By adopting research through design, this thesis goes through an iterative process where the tool is under constant improvement through quantitative testing using the Self Assessment Manikin method proposed by Lang & Bradley (1994). The tests indicate that, although colors can to some degree elicit emotions, the player’s perception of the test levels did not match the expected emotional response based on color alone for all emotional states tested. The thesis concludes that, while color-emotion association can aid in generating PCG with emotional intent, additional complementary elicitors are likely required, and further tests are needed that incorporate shapes, placement, and weather patterns.

To improve treatment of metastatic prostate cancer, the biology of metastases needs to be understood. We recently described three subtypes of prostate cancer bone metastases (MetA-C), based on differential gene expression. The aim of this study was to verify the clinical relevance of these subtypes and to explore their biology and relations to genetic drivers. Freshly-frozen metastasis samples were obtained as hormone-naive (n = 17), short-term castrated (n = 21), or castration-resistant (n = 65) from a total of 67 patients. Previously published sequencing data from 573 metastasis samples were also analyzed. Through transcriptome profiling and sample classification based on a set of predefined MetA-C-differentiating genes, we found that most metastases were heterogeneous for the MetA-C subtypes. Overall, MetA was the most common subtype, while MetB was significantly enriched in castration-resistant samples and in liver metastases, and consistently associated with poor prognosis. By gene set enrichment analysis, the phenotype of MetA was described by high androgen response, protein secretion and adipogenesis, MetB by high cell cycle activity and DNA repair, and MetC by epithelial-to-mesenchymal transition and inflammation. The MetB subtype demonstrated single nucleotide variants of RB transcriptional corepressor 1 (RB1) and loss of 21 genes at chromosome 13, including RB1, but provided independent prognostic value to those genetic aberrations. In conclusion, a distinct set of gene transcripts can be used to classify prostate cancer metastases into the subtypes MetA-C. The MetA-C subtypes show diverse biology, organ tropism, and prognosis. The MetA-C classification may be used independently, or in combination with genetic markers, primarily to identify MetB patients in need of complementary therapy to conventional androgen receptor-targeting treatments.

To improve treatment of metastatic prostate cancer, the biology of metastases needs to be understood. We recently described three subtypes of prostate cancer bone metastases (MetA-C), based on differential gene expression. The aim of this study was to verify the clinical relevance of these subtypes, and to explore their biology and relations to genetic drivers. Freshly-frozen metastasis samples were obtained as hormone-naive (n=17), short-term castrated (n=21) or castration resistant (n=65) from a total of 67 patients. Previously published sequencing data from 573 metastasis samples was also analyzed. Through transcriptome profiling and sample classification based on a set of predefined MetA-C-differentiating genes, we found that most metastases were heterogeneous for the MetA-C subtypes. Overall, MetA was the most common subtype, while MetB was significantly enriched in castration-resistant samples and in liver metastases, and consistently associated with poor prognosis. By gene set enrichment analysis, the phenotype of MetA was described by high androgen response, protein secretion and adipogenesis, MetB by high cell cycle activity and DNA repair, and MetC by epithelial-to-mesenchymal transition and inflammation. The MetB subtype demonstrated single-nucleotide variants of RB transcriptional corepressor 1 (RB1) and loss of 21 genes at chromosome 13, including RB1, but provided independent prognostic value to those genetic aberrations. In conclusion, a distinct set of gene transcripts can be used to classify prostate cancer metastases into the subtypes MetA-C. The MetA-C subtypes show diverse biology, organ tropism and prognosis. The MetA-C classification may be used independently, or in combination with genetic markers, primarily to identify MetB patients in need of complementary therapy to conventional androgen-receptor-targeting treatments.

To improve treatment of metastatic prostate cancer, the biology of metastases needs to be understood. We recently described three subtypes of prostate cancer bone metastases (MetA-C), based on differential gene expression. The aim of this study was to verify the clinical relevance of these subtypes, and to explore their biology and relations to genetic drivers. Freshly-frozen metastasis samples were obtained as hormone-naive (n=17), short-term castrated (n=21) or castration resistant (n=65) from a total of 67 patients. Previously published sequencing data from 573 metastasis samples was also analyzed. Through transcriptome profiling and sample classification based on a set of predefined MetA-C-differentiating genes, we found that most metastases were heterogeneous for the MetA-C subtypes. Overall, MetA was the most common subtype, while MetB was significantly enriched in castration-resistant samples and in liver metastases, and consistently associated with poor prognosis. By gene set enrichment analysis, the phenotype of MetA was described by high androgen response, protein secretion and adipogenesis, MetB by high cell cycle activity and DNA repair, and MetC by epithelial-to-mesenchymal transition and inflammation. The MetB subtype demonstrated single-nucleotide variants of RB transcriptional corepressor 1 (RB1) and loss of 21 genes at chromosome 13, including RB1, but provided independent prognostic value to those genetic aberrations. In conclusion, a distinct set of gene transcripts can be used to classify prostate cancer metastases into the subtypes MetA-C. The MetA-C subtypes show diverse biology, organ tropism and prognosis. The MetA-C classification may be used independently, or in combination with genetic markers, primarily to identify MetB patients in need of complementary therapy to conventional androgen-receptor-targeting treatments.

To improve treatment of metastatic prostate cancer, the biology of metastases needs to be understood. We recently described three subtypes of prostate cancer bone metastases (MetA-C), based on differential gene expression. The aim of this study was to verify the clinical relevance of these subtypes, and to explore their biology and relations to genetic drivers. Freshly-frozen metastasis samples were obtained as hormone-naive (n=17), short-term castrated (n=21) or castration resistant (n=65) from a total of 67 patients. Previously published sequencing data from 573 metastasis samples was also analyzed. Through transcriptome profiling and sample classification based on a set of predefined MetA-C-differentiating genes, we found that most metastases were heterogeneous for the MetA-C subtypes. Overall, MetA was the most common subtype, while MetB was significantly enriched in castration-resistant samples and in liver metastases, and consistently associated with poor prognosis. By gene set enrichment analysis, the phenotype of MetA was described by high androgen response, protein secretion and adipogenesis, MetB by high cell cycle activity and DNA repair, and MetC by epithelial-to-mesenchymal transition and inflammation. The MetB subtype demonstrated single-nucleotide variants of RB transcriptional corepressor 1 (RB1) and loss of 21 genes at chromosome 13, including RB1, but provided independent prognostic value to those genetic aberrations. In conclusion, a distinct set of gene transcripts can be used to classify prostate cancer metastases into the subtypes MetA-C. The MetA-C subtypes show diverse biology, organ tropism and prognosis. The MetA-C classification may be used independently, or in combination with genetic markers, primarily to identify MetB patients in need of complementary therapy to conventional androgen-receptor-targeting treatments.

Procedural Content Generation (PCG) in games often suffers from a lack of emotional connection with the player as well as a perceived sameness. This thesis aims to design and test a tool for PCG game levels for the game To the Skies! which incorporates an emotional intention based upon the color-emotion theory proposed by Fugate and Franco, 2019. Russell’s (1980) Circumplex Model of Affect was used as a foundation for the parameterization of emotions, which were implemented in a PCG test level for the game, developed in Unreal Engine. By adopting research through design, this thesis goes through an iterative process where the tool is under constant improvement through quantitative testing using the Self Assessment Manikin method proposed by Lang & Bradley (1994). The tests indicate that, although colors can to some degree elicit emotions, the player’s perception of the test levels did not match the expected emotional response based on color alone for all emotional states tested. The thesis concludes that, while color-emotion association can aid in generating PCG with emotional intent, additional complementary elicitors are likely required, and further tests are needed that incorporate shapes, placement, and weather patterns.