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Prehistoric chewed pitch has proven to be a useful source of ancient DNA, both from humans and their microbiomes. Here we present the metagenomic analysis of three pieces of chewed pitch from Huseby Klev, Sweden, that were dated to 9,890-9,540 before present. The metagenomic profile exposes a Mesolithic oral microbiome that includes opportunistic oral pathogens. We compared the data with healthy and dysbiotic microbiome datasets and we identified increased abundance of periodontitis-associated microbes. In addition, trained machine learning models predicted dysbiosis with 70-80% probability. Moreover, we identified DNA sequences from eukaryotic species such as red fox, hazelnut, red deer and apple. Our results indicate a case of poor oral health during the Scandinavian Mesolithic, and show that pitch pieces have the potential to provide information on material use, diet and oral health.

Prehistoric chewed pitch has proven to be a useful source of ancient DNA, both from humans and their microbiomes. Here we present the metagenomic analysis of three pieces of chewed pitch from Huseby Klev, Sweden, that were dated to 9,890-9,540 before present. The metagenomic profile exposes a Mesolithic oral microbiome that includes opportunistic oral pathogens. We compared the data with healthy and dysbiotic microbiome datasets and we identified increased abundance of periodontitis-associated microbes. In addition, trained machine learning models predicted dysbiosis with 70-80% probability. Moreover, we identified DNA sequences from eukaryotic species such as red fox, hazelnut, red deer and apple. Our results indicate a case of poor oral health during the Scandinavian Mesolithic, and show that pitch pieces have the potential to provide information on material use, diet and oral health.

Prehistoric chewed pitch has proven to be a useful source of ancient DNA, both from humans and their microbiomes. Here we present the metagenomic analysis of three pieces of chewed pitch from Huseby Klev, Sweden, that were dated to 9,890–9,540 before present. The metagenomic profile exposes a Mesolithic oral microbiome that includes opportunistic oral pathogens. We compared the data with healthy and dysbiotic microbiome datasets and we identified increased abundance of periodontitis-associated microbes. In addition, trained machine learning models predicted dysbiosis with 70–80% probability. Moreover, we identified DNA sequences from eukaryotic species such as red fox, hazelnut, red deer and apple. Our results indicate a case of poor oral health during the Scandinavian Mesolithic, and show that pitch pieces have the potential to provide information on material use, diet and oral health.

Prehistoric chewed pitch has proven to be a useful source of ancient DNA, both from humans and their microbiomes. Here we present the metagenomic analysis of three pieces of chewed pitch from Huseby Klev, Sweden, that were dated to 9,890-9,540 before present. The metagenomic profile exposes a Mesolithic oral microbiome that includes opportunistic oral pathogens. We compared the data with healthy and dysbiotic microbiome datasets and we identified increased abundance of periodontitis-associated microbes. In addition, trained machine learning models predicted dysbiosis with 70-80% probability. Moreover, we identified DNA sequences from eukaryotic species such as red fox, hazelnut, red deer and apple. Our results indicate a case of poor oral health during the Scandinavian Mesolithic, and show that pitch pieces have the potential to provide information on material use, diet and oral health.

Prehistoric chewed pitch has proven to be a useful source of ancient DNA, both from humans and their microbiomes. Here we present the metagenomic analysis of three pieces of chewed pitch from Huseby Klev, Sweden, that were dated to 9,890-9,540 before present. The metagenomic profile exposes a Mesolithic oral microbiome that includes opportunistic oral pathogens. We compared the data with healthy and dysbiotic microbiome datasets and we identified increased abundance of periodontitis-associated microbes. In addition, trained machine learning models predicted dysbiosis with 70-80% probability. Moreover, we identified DNA sequences from eukaryotic species such as red fox, hazelnut, red deer and apple. Our results indicate a case of poor oral health during the Scandinavian Mesolithic, and show that pitch pieces have the potential to provide information on material use, diet and oral health.

The following degree report includes the theoretical information needed to understand the retelling of a project where this report's author had the goal of building a CMS-system in the form of a block editor using the framework Laravel. This was done on-site for the company Mina Bästa Polare AB, who found a need for a CMS-system to use within their Laravel projects. This need was found through their customers' administrators needing to contact the developers for changes that otherwise could be made by the administrators if they had a CMSsystem available. The work done that is retold in this report was done in the framework Laravel, a block editor was built to be used as a CMS-system for the developers at Mina Bästa Polare to implement within their Laravel-projects. Before the development of the block editor could start the work needed to be planned, with a Gantt scheme-alike document a time estimate was made for every step in the process. The block editor was visually designed with wireframes and the database architecture was designed with an ER-diagram. The development of this block editor was done within the frameworks Laravel, Inertia, Vue and Tailwind. These techniques were used to create a full stack website that can be shown as a first example of how this CMS-system can be used within Laravel-projects. With this system available to them both the developers and customers of Mina Bästa Polare will experience a smoother running workday, Föreliggande rapport presenterar den teoretiska information som behövs för att förstå efterkommande återberättande av ett projektarbete där målet var att rapportens författare skulle bygga ett CMS-system i form av en blockeditor inom ramverket Laravel. Projektarbetet utfördes på plats hos företaget Mina Bästa Polare AB, en webbyrå baserad i Östersund som upptäckt ett behov av ett CMS-system i form av en blockeditor till sina Laravel-projekt. tillgång till ett sådant CMS-system. Ett mål är att editorn skall bli så “decoupled“ som möjligt, vilket betyder att i högsta möjliga mån skall kunna implementeras i vilket Laravel-projekt som helst. Innan utvecklingen av blockeditorn påbörjades så strukturerades arbetet upp genom att det tidsplanerades med hjälp av en tidplan som liknar ett Gantt-schema vilket estimerar en tidsaspekt för varje steg i processen. Sedan påbörjades blockeditorns visuella design vilket gjordes med wireframes följt av att databasen arkitektur designades genom ett ER-diagram. Utvecklingen utfördes i ramverken Laravel, Inertia, Vue och Tailwind. Dessa tekniker användes för att i slutändan resultera i en fullstack webbplats som kan visas upp som ett första exempel på hur denna CMS-system kan användas inom Laravel-projekt. Med detta system tillgängligt kan nu inte bara Mina Bästa Polares utvecklare utan även deras kunder få en smidigare vardag när de använder detta system.

Prehistoric chewed pitch has proven to be a useful source of ancient DNA, both from humans and their microbiomes. Here we present the metagenomic analysis of three pieces of chewed pitch from Huseby Klev, Sweden, that were dated to 9,890-9,540 before present. The metagenomic profile exposes a Mesolithic oral microbiome that includes opportunistic oral pathogens. We compared the data with healthy and dysbiotic microbiome datasets and we identified increased abundance of periodontitis-associated microbes. In addition, trained machine learning models predicted dysbiosis with 70-80% probability. Moreover, we identified DNA sequences from eukaryotic species such as red fox, hazelnut, red deer and apple. Our results indicate a case of poor oral health during the Scandinavian Mesolithic, and show that pitch pieces have the potential to provide information on material use, diet and oral health.

Prehistoric chewed pitch has proven to be a useful source of ancient DNA, both from humans and their microbiomes. Here we present the metagenomic analysis of three pieces of chewed pitch from Huseby Klev, Sweden, that were dated to 9,890-9,540 before present. The metagenomic profile exposes a Mesolithic oral microbiome that includes opportunistic oral pathogens. We compared the data with healthy and dysbiotic microbiome datasets and we identified increased abundance of periodontitis-associated microbes. In addition, trained machine learning models predicted dysbiosis with 70-80% probability. Moreover, we identified DNA sequences from eukaryotic species such as red fox, hazelnut, red deer and apple. Our results indicate a case of poor oral health during the Scandinavian Mesolithic, and show that pitch pieces have the potential to provide information on material use, diet and oral health.

The following degree report includes the theoretical information needed to understand the retelling of a project where this report's author had the goal of building a CMS-system in the form of a block editor using the framework Laravel. This was done on-site for the company Mina Bästa Polare AB, who found a need for a CMS-system to use within their Laravel projects. This need was found through their customers' administrators needing to contact the developers for changes that otherwise could be made by the administrators if they had a CMSsystem available. The work done that is retold in this report was done in the framework Laravel, a block editor was built to be used as a CMS-system for the developers at Mina Bästa Polare to implement within their Laravel-projects. Before the development of the block editor could start the work needed to be planned, with a Gantt scheme-alike document a time estimate was made for every step in the process. The block editor was visually designed with wireframes and the database architecture was designed with an ER-diagram. The development of this block editor was done within the frameworks Laravel, Inertia, Vue and Tailwind. These techniques were used to create a full stack website that can be shown as a first example of how this CMS-system can be used within Laravel-projects. With this system available to them both the developers and customers of Mina Bästa Polare will experience a smoother running workday, Föreliggande rapport presenterar den teoretiska information som behövs för att förstå efterkommande återberättande av ett projektarbete där målet var att rapportens författare skulle bygga ett CMS-system i form av en blockeditor inom ramverket Laravel. Projektarbetet utfördes på plats hos företaget Mina Bästa Polare AB, en webbyrå baserad i Östersund som upptäckt ett behov av ett CMS-system i form av en blockeditor till sina Laravel-projekt. tillgång till ett sådant CMS-system. Ett mål är att editorn skall bli så “decoupled“ som möjligt, vilket betyder att i högsta möjliga mån skall kunna implementeras i vilket Laravel-projekt som helst. Innan utvecklingen av blockeditorn påbörjades så strukturerades arbetet upp genom att det tidsplanerades med hjälp av en tidplan som liknar ett Gantt-schema vilket estimerar en tidsaspekt för varje steg i processen. Sedan påbörjades blockeditorns visuella design vilket gjordes med wireframes följt av att databasen arkitektur designades genom ett ER-diagram. Utvecklingen utfördes i ramverken Laravel, Inertia, Vue och Tailwind. Dessa tekniker användes för att i slutändan resultera i en fullstack webbplats som kan visas upp som ett första exempel på hur denna CMS-system kan användas inom Laravel-projekt. Med detta system tillgängligt kan nu inte bara Mina Bästa Polares utvecklare utan även deras kunder få en smidigare vardag när de använder detta system.

Technological and scientific advancements over the past 30-40 years make it possible to fabricate nanometer-sized systems where fluctuations and quantum effects are important features. These systems can be controlled and measured with high accuracy, making them suitable for exploring fundamental aspects of the microscopic world. This thesis makes contributions in this direction, focusing on the theory of continuous, Markovian feedback control and stochastic as well as quantum thermodynamics.In Paper I and III, we study an implementation of Maxwell’s demon in a double quantum dot. A feedback protocol, based on charge detection, transfers electrons against an external voltage bias, without performing any net work. The protocol is studied for both classical and quantum dynamics. We characterize the electronic transport properties, explore information-to-work conversion with realistic detector models, as well as the quantum-to-classical transition.Paper II introduces a novel master equation for continuous, Markovian feedback control. This equation describes the dynamics of a quantum system and a detector with finite bandwidth. For a fast detector, the equation reduces to a Markovian master equation for the system alone. This equation can describe protocols that depend linearly as well as nonlinearly on the measured signal. For linear protocols, this equation coincides with theWiseman-Milburn equation, illustrating a compelling connection to previous work in the field.Paper IV investigates a specific feedback protocol for increasing the entanglement generation in an autonomous thermal machine. Under optimal conditions, we find that the protocol significantly increases the entanglement. The entanglement violates the CHSH inequality and can uphold quantum teleportation.Paper V presents a setup for generating maximally entangled states in autonomous thermal machines. First, we show that maximal bipartite entanglement can be generated in a system of three qubits. This is lat

The lethal malaria parasite Plasmodium falciparum needs to constantly respond and adapt to changes within the human host in order to survive and transmit. One such change is composed of nutritional limitation, which is augmented with increased parasite loads and intimately linked to severe disease development. Extracellular vesicles released from infected red blood cells have been proposed as important mediators of disease pathogenesis and intercellular communication but whether important for the parasite response to nutritional availability is unknown. Therefore, we investigated the abundance and small RNA cargo of extracellular vesicles released upon short-term nutritional starvation of P. falciparum in vitro cultures. We show that primarily ring-stage parasite cultures respond to glucose and amino acid deprivation with an increased release of extracellular vesicles. Small RNA sequencing of these extracellular vesicles further revealed human miRNAs and parasitic tRNA fragments as the main constituent biotypes. Short-term starvations led to alterations in the transcriptomic profile, most notably in terms of the over-represented biotypes. These data suggest a potential role for extracellular vesicles released from P. falciparum infected red blood cells in the response to nutritional perturbations, their potential as prognostic biomarkers and point towards an evolutionary conserved role among protozoan parasites.

The lethal malaria parasite Plasmodium falciparum needs to constantly respond and adapt to changes within the human host in order to survive and transmit. One such change is composed of nutritional limitation, which is augmented with increased parasite loads and intimately linked to severe disease development. Extracellular vesicles released from infected red blood cells have been proposed as important mediators of disease pathogenesis and intercellular communication but whether important for the parasite response to nutritional availability is unknown. Therefore, we investigated the abundance and small RNA cargo of extracellular vesicles released upon short-term nutritional starvation of P. falciparum in vitro cultures. We show that primarily ring-stage parasite cultures respond to glucose and amino acid deprivation with an increased release of extracellular vesicles. Small RNA sequencing of these extracellular vesicles further revealed human miRNAs and parasitic tRNA fragments as the main constituent biotypes. Short-term starvations led to alterations in the transcriptomic profile, most notably in terms of the over-represented biotypes. These data suggest a potential role for extracellular vesicles released from P. falciparum infected red blood cells in the response to nutritional perturbations, their potential as prognostic biomarkers and point towards an evolutionary conserved role among protozoan parasites.

Paleogenomics continues to yield valuable insights into the evolution, population dynamics, and ecology of our ancestors and other extinct species. However, DNA sequencing cannot reveal tissue-specific gene expression, cellular identity, or gene regulation, which are only attainable at the transcriptional level. Pioneering studies have shown that useful RNA can be extracted from ancient specimens preserved in permafrost and historical skins from extant canids, but no attempts have been made so far on extinct species. We extract, sequence, and analyze historical RNA from muscle and skin tissue of a ∼130-year-old Tasmanian tiger (Thylacinus cynocephalus) preserved in desiccation at room temperature in a museum collection. The transcriptional profiles closely resemble those of extant species, revealing specific anatomical features such as slow muscle fibers or blood infiltration. Metatranscriptomic analysis, RNA damage, tissue-specific RNA profiles, and expression hotspots genome-wide further confirm the thylacine origin of the sequences. RNA sequences are used to improve protein-coding and noncoding annotations, evidencing missing exonic loci and the location of ribosomal RNA genes while increasing the number of annotated thylacine microRNAs from 62 to 325. We discover a thylacine-specific microRNA isoform that could not have been confirmed without RNA evidence. Finally, we detect traces of RNA viruses, suggesting the possibility of profiling viral evolution. Our results represent the first successful attempt to obtain transcriptional profiles from an extinct animal species, providing thought-to-be-lost information on gene expression dynamics. These findings hold promising implications for the study of RNA molecules across the vast collections of natural history museums and from well-preserved permafrost remains.

The lethal malaria parasite Plasmodium falciparum needs to constantly respond and adapt to changes within the human host in order to survive and transmit. One such change is composed of nutritional limitation, which is augmented with increased parasite loads and intimately linked to severe disease development. Extracellular vesicles released from infected red blood cells have been proposed as important mediators of disease pathogenesis and intercellular communication but whether important for the parasite response to nutritional availability is unknown. Therefore, we investigated the abundance and small RNA cargo of extracellular vesicles released upon short-term nutritional starvation of P. falciparum in vitro cultures. We show that primarily ring-stage parasite cultures respond to glucose and amino acid deprivation with an increased release of extracellular vesicles. Small RNA sequencing of these extracellular vesicles further revealed human miRNAs and parasitic tRNA fragments as the main constituent biotypes. Short-term starvations led to alterations in the transcriptomic profile, most notably in terms of the over-represented biotypes. These data suggest a potential role for extracellular vesicles released from P. falciparum infected red blood cells in the response to nutritional perturbations, their potential as prognostic biomarkers and point towards an evolutionary conserved role among protozoan parasites.

A computationally efficient method for marginal maximum likelihood estimation of multiple group generalized linear latent variable models for categorical data is introduced. The approach utilizes second-order Laplace approximations of the integrals in the likelihood function. It is demonstrated how second-order Laplace approximations can be utilized highly efficiently for generalized linear latent variable models by considering symmetries that exist for many types of model structures. In a simulation with binary observed variables and four correlated latent variables in four groups, the method has similar bias and mean squared error compared to adaptive Gauss-Hermite quadrature with five quadrature points while substantially improving computational efficiency. An empirical example from a large-scale educational assessment illustrates the accuracy and computational efficiency of the method when compared against adaptive Gauss-Hermite quadrature with three, five, and 13 quadrature points.

BackgroundSpatial properties of a dose distribution, such as volumes of contiguous hot spots, are of clinical importance in treatment planning for high dose-rate brachytherapy (HDR BT). We have in an earlier study developed an optimization model that reduces the prevalence of contiguous hot spots by modifying a tentative treatment plan. PurposeThe aim of this study is to incorporate the correction of hot spots in a standard inverse planning workflow and to validate the integrated model in a clinical treatment planning system. The spatial function is included in the objective function for the inverse planning, as opposed to in the previous study where it was applied as a separate post-processing step. Our aim is to demonstrate that fine-adjustments of dose distributions, which are often performed manually in todays clinical practice, can be automated. MethodsA spatial optimization function was introduced in the treatment planning system RayStation (RaySearch Laboratories AB, Stockholm, Sweden) via a research interface. A series of 10 consecutive prostate patients treated with HDR BT was retrospectively replanned with and without the spatial function. ResultsOptimization with the spatial function decreased the volume of the largest contiguous hot spot by on average 31%, compared to if the function was not included. The volume receiving at least 200% of the prescription dose decreased by on average 11%. Target coverage, measured as the fractions of the clinical target volume (CTV) and the planning target volume (PTV) receiving at least the prescription dose, was virtually unchanged (less than a percent change for both metrics). Organs-at-risk received comparable or slightly decreased doses if the spatial function was included in the optimization model. ConclusionsOptimization of spatial properties such as the volume of contiguous hot spots can be integrated in a standard inverse planning workflow for brachytherapy, and need not be conducted as a separate post-processin, Funding: Vetenskapsradet (VR) [VR-NT 2019-155 05416]; Cancerfonden (Swedish Cancer Society) [CAN 2017/1029, Pj 211788]

BackgroundSpatial properties of a dose distribution, such as volumes of contiguous hot spots, are of clinical importance in treatment planning for high dose-rate brachytherapy (HDR BT). We have in an earlier study developed an optimization model that reduces the prevalence of contiguous hot spots by modifying a tentative treatment plan. PurposeThe aim of this study is to incorporate the correction of hot spots in a standard inverse planning workflow and to validate the integrated model in a clinical treatment planning system. The spatial function is included in the objective function for the inverse planning, as opposed to in the previous study where it was applied as a separate post-processing step. Our aim is to demonstrate that fine-adjustments of dose distributions, which are often performed manually in todays clinical practice, can be automated. MethodsA spatial optimization function was introduced in the treatment planning system RayStation (RaySearch Laboratories AB, Stockholm, Sweden) via a research interface. A series of 10 consecutive prostate patients treated with HDR BT was retrospectively replanned with and without the spatial function. ResultsOptimization with the spatial function decreased the volume of the largest contiguous hot spot by on average 31%, compared to if the function was not included. The volume receiving at least 200% of the prescription dose decreased by on average 11%. Target coverage, measured as the fractions of the clinical target volume (CTV) and the planning target volume (PTV) receiving at least the prescription dose, was virtually unchanged (less than a percent change for both metrics). Organs-at-risk received comparable or slightly decreased doses if the spatial function was included in the optimization model. ConclusionsOptimization of spatial properties such as the volume of contiguous hot spots can be integrated in a standard inverse planning workflow for brachytherapy, and need not be conducted as a separate post-processin, Funding: Vetenskapsradet (VR) [VR-NT 2019-155 05416]; Cancerfonden (Swedish Cancer Society) [CAN 2017/1029, Pj 211788]

BackgroundSpatial properties of a dose distribution, such as volumes of contiguous hot spots, are of clinical importance in treatment planning for high dose-rate brachytherapy (HDR BT). We have in an earlier study developed an optimization model that reduces the prevalence of contiguous hot spots by modifying a tentative treatment plan. PurposeThe aim of this study is to incorporate the correction of hot spots in a standard inverse planning workflow and to validate the integrated model in a clinical treatment planning system. The spatial function is included in the objective function for the inverse planning, as opposed to in the previous study where it was applied as a separate post-processing step. Our aim is to demonstrate that fine-adjustments of dose distributions, which are often performed manually in todays clinical practice, can be automated. MethodsA spatial optimization function was introduced in the treatment planning system RayStation (RaySearch Laboratories AB, Stockholm, Sweden) via a research interface. A series of 10 consecutive prostate patients treated with HDR BT was retrospectively replanned with and without the spatial function. ResultsOptimization with the spatial function decreased the volume of the largest contiguous hot spot by on average 31%, compared to if the function was not included. The volume receiving at least 200% of the prescription dose decreased by on average 11%. Target coverage, measured as the fractions of the clinical target volume (CTV) and the planning target volume (PTV) receiving at least the prescription dose, was virtually unchanged (less than a percent change for both metrics). Organs-at-risk received comparable or slightly decreased doses if the spatial function was included in the optimization model. ConclusionsOptimization of spatial properties such as the volume of contiguous hot spots can be integrated in a standard inverse planning workflow for brachytherapy, and need not be conducted as a separate post-processin, Funding: Vetenskapsradet (VR) [VR-NT 2019-155 05416]; Cancerfonden (Swedish Cancer Society) [CAN 2017/1029, Pj 211788]

Syfte - Precis som samhället i övrigt digitaliserar Försvarsmakten sin verksamhet i ökande grad. Det höjer förmågan men ökar riskerna för cyberangrepp. Som en av flera åtgärder introducerade därför Försvarsmakten personalkategorin cybersoldat. Syftet med denna studie är att utreda hur införandet av cybersoldater har hanterats inom Försvarsmaktens organisation och på vilket sätt det har påverkat cyberförsvarsförmågan. Design/metod/approach - Studien är genomförd som en kvalitativ intervjustudie där respondenter från olika organisationsnivåer inom Försvarsmakten har gett sin syn på cybersoldatinförandet. Detta för att följa cybersoldatsrollen ur ett livscykelperspektiv från planeringsstadiet genom utbildningen och vidare mot karriären. Slutsatser – Resultatet av studien visar att strategin för uppbyggnaden av cyberförsvaret och cybersoldaternas roll inte är tillräckligt väl kommunicerad inom Försvarsmaktens organisation. Studien visar att det behövs ett livscykelperspektiv på cybersoldaternas kompetensutveckling som sträcker sig bortom värnplikten, vilket kan ses som ett paradigmskifte för hur Försvarsmakten normalt sett utbildar och hanterare krigsplacerad personal., Purpose - Just like society in general, the Swedish Armed Forces are increasingly digitizing their operations. It increases capability but increases the risks of cyberattacks. As one of several measures, the Swedish Armed Forces therefore introduced the Cyber Soldier personnel category. The purpose of this study is to investigate how the introduction of cyber soldiers has been handled within the Swedish Armed Forces' organization and in what way it has affected cyber defence capability. Design/methodology/approach - The study was conducted as a qualitative interview study where respondents from different organizational levels gave their views on the cyber soldier introduction. This by following the cyber soldier role from a life cycle perspective from the planning stage through the education and on to the career. Findings - The findings of the study shows that the strategy for building up cyber defence and the role of cyber soldiers are not sufficiently well communicated within the Armed Forces. The study shows that there is a need for a life cycle perspective for cyber soldiers' competence development that extends beyond conscription, which can be seen as a paradigm shift for how the Armed Forces normally train and handle war-deployed personnel.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common upper respiratory tract complication where the pathogenesis is largely unknown. Herein, we investigated the transcriptome profile in nasal mucosa biopsies of CRSwNP patients and healthy individuals. We further integrated the transcriptomics data with genes located in chromosomal regions containing genome-wide significant gene variants for COVID-19. Among the most significantly upregulated genes in polyp mucosa were CCL18, CLEC4G, CCL13 and SLC9A3. Pathways involving "Ciliated epithelial cells" were the most differentially expressed molecular pathways when polyp mucosa and non-polyp mucosa from the same patient was compared. Natural killer T-cell (NKT) and viral pathways were the most statistically significant pathways in the mucosa of CRSwNP patients compared with those of healthy control individuals. Upregulated genes in polyp mucosa, located within the genome-wide associated regions of COVID-19, included LZTFL1, CCR9, SLC6A20, IFNAR1, IFNAR2 and IL10RB. Interestingly, the second most over-expressed gene in our study, CLEC4G, has been shown to bind directly to SARS-CoV-2 spike's N-terminal domain and mediate its entry and infection. Our results on altered expression of genes related to cilia and viruses point to the de-regulation of viral defenses in CRSwNP patients, and may give clues to future intervention strategies.

A computationally efficient method for marginal maximum likelihood estimation of multiple group generalized linear latent variable models for categorical data is introduced. The approach utilizes second-order Laplace approximations of the integrals in the likelihood function. It is demonstrated how second-order Laplace approximations can be utilized highly efficiently for generalized linear latent variable models by considering symmetries that exist for many types of model structures. In a simulation with binary observed variables and four correlated latent variables in four groups, the method has similar bias and mean squared error compared to adaptive Gauss-Hermite quadrature with five quadrature points while substantially improving computational efficiency. An empirical example from a large-scale educational assessment illustrates the accuracy and computational efficiency of the method when compared against adaptive Gauss-Hermite quadrature with three, five, and 13 quadrature points.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common upper respiratory tract complication where the pathogenesis is largely unknown. Herein, we investigated the transcriptome profile in nasal mucosa biopsies of CRSwNP patients and healthy individuals. We further integrated the transcriptomics data with genes located in chromosomal regions containing genome-wide significant gene variants for COVID-19. Among the most significantly upregulated genes in polyp mucosa were CCL18, CLEC4G, CCL13 and SLC9A3. Pathways involving "Ciliated epithelial cells" were the most differentially expressed molecular pathways when polyp mucosa and non-polyp mucosa from the same patient was compared. Natural killer T-cell (NKT) and viral pathways were the most statistically significant pathways in the mucosa of CRSwNP patients compared with those of healthy control individuals. Upregulated genes in polyp mucosa, located within the genome-wide associated regions of COVID-19, included LZTFL1, CCR9, SLC6A20, IFNAR1, IFNAR2 and IL10RB. Interestingly, the second most over-expressed gene in our study, CLEC4G, has been shown to bind directly to SARS-CoV-2 spike's N-terminal domain and mediate its entry and infection. Our results on altered expression of genes related to cilia and viruses point to the de-regulation of viral defenses in CRSwNP patients, and may give clues to future intervention strategies.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common upper respiratory tract complication where the pathogenesis is largely unknown. Herein, we investigated the transcriptome profile in nasal mucosa biopsies of CRSwNP patients and healthy individuals. We further integrated the transcriptomics data with genes located in chromosomal regions containing genome-wide significant gene variants for COVID-19. Among the most significantly upregulated genes in polyp mucosa were CCL18, CLEC4G, CCL13 and SLC9A3. Pathways involving "Ciliated epithelial cells" were the most differentially expressed molecular pathways when polyp mucosa and non-polyp mucosa from the same patient was compared. Natural killer T-cell (NKT) and viral pathways were the most statistically significant pathways in the mucosa of CRSwNP patients compared with those of healthy control individuals. Upregulated genes in polyp mucosa, located within the genome-wide associated regions of COVID-19, included LZTFL1, CCR9, SLC6A20, IFNAR1, IFNAR2 and IL10RB. Interestingly, the second most over-expressed gene in our study, CLEC4G, has been shown to bind directly to SARS-CoV-2 spike's N-terminal domain and mediate its entry and infection. Our results on altered expression of genes related to cilia and viruses point to the de-regulation of viral defenses in CRSwNP patients, and may give clues to future intervention strategies.

A computationally efficient method for marginal maximum likelihood estimation of multiple group generalized linear latent variable models for categorical data is introduced. The approach utilizes second-order Laplace approximations of the integrals in the likelihood function. It is demonstrated how second-order Laplace approximations can be utilized highly efficiently for generalized linear latent variable models by considering symmetries that exist for many types of model structures. In a simulation with binary observed variables and four correlated latent variables in four groups, the method has similar bias and mean squared error compared to adaptive Gauss-Hermite quadrature with five quadrature points while substantially improving computational efficiency. An empirical example from a large-scale educational assessment illustrates the accuracy and computational efficiency of the method when compared against adaptive Gauss-Hermite quadrature with three, five, and 13 quadrature points.

A computationally efficient method for marginal maximum likelihood estimation of multiple group generalized linear latent variable models for categorical data is introduced. The approach utilizes second-order Laplace approximations of the integrals in the likelihood function. It is demonstrated how second-order Laplace approximations can be utilized highly efficiently for generalized linear latent variable models by considering symmetries that exist for many types of model structures. In a simulation with binary observed variables and four correlated latent variables in four groups, the method has similar bias and mean squared error compared to adaptive Gauss-Hermite quadrature with five quadrature points while substantially improving computational efficiency. An empirical example from a large-scale educational assessment illustrates the accuracy and computational efficiency of the method when compared against adaptive Gauss-Hermite quadrature with three, five, and 13 quadrature points.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common upper respiratory tract complication where the pathogenesis is largely unknown. Herein, we investigated the transcriptome profile in nasal mucosa biopsies of CRSwNP patients and healthy individuals. We further integrated the transcriptomics data with genes located in chromosomal regions containing genome-wide significant gene variants for COVID-19. Among the most significantly upregulated genes in polyp mucosa were CCL18, CLEC4G, CCL13 and SLC9A3. Pathways involving "Ciliated epithelial cells" were the most differentially expressed molecular pathways when polyp mucosa and non-polyp mucosa from the same patient was compared. Natural killer T-cell (NKT) and viral pathways were the most statistically significant pathways in the mucosa of CRSwNP patients compared with those of healthy control individuals. Upregulated genes in polyp mucosa, located within the genome-wide associated regions of COVID-19, included LZTFL1, CCR9, SLC6A20, IFNAR1, IFNAR2 and IL10RB. Interestingly, the second most over-expressed gene in our study, CLEC4G, has been shown to bind directly to SARS-CoV-2 spike's N-terminal domain and mediate its entry and infection. Our results on altered expression of genes related to cilia and viruses point to the de-regulation of viral defenses in CRSwNP patients, and may give clues to future intervention strategies.

The lethal malaria parasite Plasmodium falciparum needs to constantly respond and adapt to changes within the human host in order to survive and transmit. One such change is composed of nutritional limitation, which is augmented with increased parasite loads and intimately linked to severe disease development. Extracellular vesicles released from infected red blood cells have been proposed as important mediators of disease pathogenesis and intercellular communication but whether important for the parasite response to nutritional availability is unknown. Therefore, we investigated the abundance and small RNA cargo of extracellular vesicles released upon short-term nutritional starvation of P. falciparum in vitro cultures. We show that primarily ring-stage parasite cultures respond to glucose and amino acid deprivation with an increased release of extracellular vesicles. Small RNA sequencing of these extracellular vesicles further revealed human miRNAs and parasitic tRNA fragments as the main constituent biotypes. Short-term starvations led to alterations in the transcriptomic profile, most notably in terms of the over-represented biotypes. These data suggest a potential role for extracellular vesicles released from P. falciparum infected red blood cells in the response to nutritional perturbations, their potential as prognostic biomarkers and point towards an evolutionary conserved role among protozoan parasites.

The lethal malaria parasite Plasmodium falciparum needs to constantly respond and adapt to changes within the human host in order to survive and transmit. One such change is composed of nutritional limitation, which is augmented with increased parasite loads and intimately linked to severe disease development. Extracellular vesicles released from infected red blood cells have been proposed as important mediators of disease pathogenesis and intercellular communication but whether important for the parasite response to nutritional availability is unknown. Therefore, we investigated the abundance and small RNA cargo of extracellular vesicles released upon short-term nutritional starvation of P. falciparum in vitro cultures. We show that primarily ring-stage parasite cultures respond to glucose and amino acid deprivation with an increased release of extracellular vesicles. Small RNA sequencing of these extracellular vesicles further revealed human miRNAs and parasitic tRNA fragments as the main constituent biotypes. Short-term starvations led to alterations in the transcriptomic profile, most notably in terms of the over-represented biotypes. These data suggest a potential role for extracellular vesicles released from P. falciparum infected red blood cells in the response to nutritional perturbations, their potential as prognostic biomarkers and point towards an evolutionary conserved role among protozoan parasites.

BackgroundSpatial properties of a dose distribution, such as volumes of contiguous hot spots, are of clinical importance in treatment planning for high dose-rate brachytherapy (HDR BT). We have in an earlier study developed an optimization model that reduces the prevalence of contiguous hot spots by modifying a tentative treatment plan. PurposeThe aim of this study is to incorporate the correction of hot spots in a standard inverse planning workflow and to validate the integrated model in a clinical treatment planning system. The spatial function is included in the objective function for the inverse planning, as opposed to in the previous study where it was applied as a separate post-processing step. Our aim is to demonstrate that fine-adjustments of dose distributions, which are often performed manually in todays clinical practice, can be automated. MethodsA spatial optimization function was introduced in the treatment planning system RayStation (RaySearch Laboratories AB, Stockholm, Sweden) via a research interface. A series of 10 consecutive prostate patients treated with HDR BT was retrospectively replanned with and without the spatial function. ResultsOptimization with the spatial function decreased the volume of the largest contiguous hot spot by on average 31%, compared to if the function was not included. The volume receiving at least 200% of the prescription dose decreased by on average 11%. Target coverage, measured as the fractions of the clinical target volume (CTV) and the planning target volume (PTV) receiving at least the prescription dose, was virtually unchanged (less than a percent change for both metrics). Organs-at-risk received comparable or slightly decreased doses if the spatial function was included in the optimization model. ConclusionsOptimization of spatial properties such as the volume of contiguous hot spots can be integrated in a standard inverse planning workflow for brachytherapy, and need not be conducted as a separate post-processin, Funding: Vetenskapsradet (VR) [VR-NT 2019-155 05416]; Cancerfonden (Swedish Cancer Society) [CAN 2017/1029, Pj 211788]

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common upper respiratory tract complication where the pathogenesis is largely unknown. Herein, we investigated the transcriptome profile in nasal mucosa biopsies of CRSwNP patients and healthy individuals. We further integrated the transcriptomics data with genes located in chromosomal regions containing genome-wide significant gene variants for COVID-19. Among the most significantly upregulated genes in polyp mucosa were CCL18, CLEC4G, CCL13 and SLC9A3. Pathways involving "Ciliated epithelial cells" were the most differentially expressed molecular pathways when polyp mucosa and non-polyp mucosa from the same patient was compared. Natural killer T-cell (NKT) and viral pathways were the most statistically significant pathways in the mucosa of CRSwNP patients compared with those of healthy control individuals. Upregulated genes in polyp mucosa, located within the genome-wide associated regions of COVID-19, included LZTFL1, CCR9, SLC6A20, IFNAR1, IFNAR2 and IL10RB. Interestingly, the second most over-expressed gene in our study, CLEC4G, has been shown to bind directly to SARS-CoV-2 spike's N-terminal domain and mediate its entry and infection. Our results on altered expression of genes related to cilia and viruses point to the de-regulation of viral defenses in CRSwNP patients, and may give clues to future intervention strategies.

Syfte - Precis som samhället i övrigt digitaliserar Försvarsmakten sin verksamhet i ökande grad. Det höjer förmågan men ökar riskerna för cyberangrepp. Som en av flera åtgärder introducerade därför Försvarsmakten personalkategorin cybersoldat. Syftet med denna studie är att utreda hur införandet av cybersoldater har hanterats inom Försvarsmaktens organisation och på vilket sätt det har påverkat cyberförsvarsförmågan. Design/metod/approach - Studien är genomförd som en kvalitativ intervjustudie där respondenter från olika organisationsnivåer inom Försvarsmakten har gett sin syn på cybersoldatinförandet. Detta för att följa cybersoldatsrollen ur ett livscykelperspektiv från planeringsstadiet genom utbildningen och vidare mot karriären. Slutsatser – Resultatet av studien visar att strategin för uppbyggnaden av cyberförsvaret och cybersoldaternas roll inte är tillräckligt väl kommunicerad inom Försvarsmaktens organisation. Studien visar att det behövs ett livscykelperspektiv på cybersoldaternas kompetensutveckling som sträcker sig bortom värnplikten, vilket kan ses som ett paradigmskifte för hur Försvarsmakten normalt sett utbildar och hanterare krigsplacerad personal., Purpose - Just like society in general, the Swedish Armed Forces are increasingly digitizing their operations. It increases capability but increases the risks of cyberattacks. As one of several measures, the Swedish Armed Forces therefore introduced the Cyber Soldier personnel category. The purpose of this study is to investigate how the introduction of cyber soldiers has been handled within the Swedish Armed Forces' organization and in what way it has affected cyber defence capability. Design/methodology/approach - The study was conducted as a qualitative interview study where respondents from different organizational levels gave their views on the cyber soldier introduction. This by following the cyber soldier role from a life cycle perspective from the planning stage through the education and on to the career. Findings - The findings of the study shows that the strategy for building up cyber defence and the role of cyber soldiers are not sufficiently well communicated within the Armed Forces. The study shows that there is a need for a life cycle perspective for cyber soldiers' competence development that extends beyond conscription, which can be seen as a paradigm shift for how the Armed Forces normally train and handle war-deployed personnel.

A computationally efficient method for marginal maximum likelihood estimation of multiple group generalized linear latent variable models for categorical data is introduced. The approach utilizes second-order Laplace approximations of the integrals in the likelihood function. It is demonstrated how second-order Laplace approximations can be utilized highly efficiently for generalized linear latent variable models by considering symmetries that exist for many types of model structures. In a simulation with binary observed variables and four correlated latent variables in four groups, the method has similar bias and mean squared error compared to adaptive Gauss-Hermite quadrature with five quadrature points while substantially improving computational efficiency. An empirical example from a large-scale educational assessment illustrates the accuracy and computational efficiency of the method when compared against adaptive Gauss-Hermite quadrature with three, five, and 13 quadrature points.

BackgroundSpatial properties of a dose distribution, such as volumes of contiguous hot spots, are of clinical importance in treatment planning for high dose-rate brachytherapy (HDR BT). We have in an earlier study developed an optimization model that reduces the prevalence of contiguous hot spots by modifying a tentative treatment plan. PurposeThe aim of this study is to incorporate the correction of hot spots in a standard inverse planning workflow and to validate the integrated model in a clinical treatment planning system. The spatial function is included in the objective function for the inverse planning, as opposed to in the previous study where it was applied as a separate post-processing step. Our aim is to demonstrate that fine-adjustments of dose distributions, which are often performed manually in todays clinical practice, can be automated. MethodsA spatial optimization function was introduced in the treatment planning system RayStation (RaySearch Laboratories AB, Stockholm, Sweden) via a research interface. A series of 10 consecutive prostate patients treated with HDR BT was retrospectively replanned with and without the spatial function. ResultsOptimization with the spatial function decreased the volume of the largest contiguous hot spot by on average 31%, compared to if the function was not included. The volume receiving at least 200% of the prescription dose decreased by on average 11%. Target coverage, measured as the fractions of the clinical target volume (CTV) and the planning target volume (PTV) receiving at least the prescription dose, was virtually unchanged (less than a percent change for both metrics). Organs-at-risk received comparable or slightly decreased doses if the spatial function was included in the optimization model. ConclusionsOptimization of spatial properties such as the volume of contiguous hot spots can be integrated in a standard inverse planning workflow for brachytherapy, and need not be conducted as a separate post-processin, Funding: Vetenskapsradet (VR) [VR-NT 2019-155 05416]; Cancerfonden (Swedish Cancer Society) [CAN 2017/1029, Pj 211788]

The thesis seeks to investigate whether there is a general duty to give notice in the event of a breach of contract in situations not covered by a statutory regulation. A particular purpose is to clarify the inner nature of the legal institute of notification when it comes to contracts on complex intangible services, such as legal advice and investigation services. A legal dogmatic method is applied. Supported by case law from the Supreme Court as well as by doctrine, the conclusion is that there is indeed a general duty to give notice in the event of a breach of contract in Swedish law. At the same time, the author identifies certain ambiguities in the scope of this duty. A recent case seems to indicate that the general duty to give notice is limited to breach of contract in the strict sense. Another ambiguity is whether preclusion is the exclusive legal consequence of a failure to notify, or whether less intrusive consequences may follow. For complex intangible services, the investigation indicates that the duty to give notice starts even before actual knowledge of the breach of contract, which is surprising since there is no obligation to investigate the performance of such services in Swedish law. The length of the notification period is estimated to be around six months for advanced complex intangible services, such as legal advice, and about a month or two shorter for somewhat less advanced services, such as investigation of real estate. This is to be seen as the main rule, but a balanced assessment of the circumstances in casu must be made to determine the length of the notification period in the individual case. Finally, a proposal for a clarified and modified legal regulation is presented de lege ferenda, which emphasizes that the duty to give notice applies to all forms of breach of contract and that, as a default rule, preclusion is the legal consequence in case of a failure to notify. A less intrusive alternative rule is suggested for situations where th, Uppsatsen syftar till att utreda rättsläget i frågan om en allmän reklamationsplikt vid avtalsbrott i situationer som inte omfattas av någon lagreglering. Ett särskilt syfte är att klargöra reklamationsplikten närmare beskaffenhet när det handlar om avtal om komplexa immateriella tjänster, såsom rådgivnings- och undersökningstjänster. En rättsdogmatisk metod tillämpas. Utredningen kommer fram till att det finns en allmän reklamationsplikt vid avtalsbrott i svensk rätt. Slutsatsen stöds av rättspraxis från Högsta domstolen liksom av doktrin. Samtidigt identifierar författaren vissa oklarheter i den allmänna reklamationspliktens omfattning. Ett färskt rättsfall kan uppfattas som att den allmänna reklamationsplikten är begränsad till avtalsbrott i strikt mening. En annan oklarhet är om rättsföljden vid försummad reklamation alltid är preklusion, eller om mindre ingripande konsekvenser kan bli aktuella. Författaren gör bedömningen att det rättsliga stödet är svagt för någon annan rättsföljd än preklusion. Utredningen visar att reklamationsplikten vid komplexa immateriella tjänster startar redan före faktisk vetskap om avtalsbrottet, vilket är överraskande eftersom undersökningsplikt saknas. Reklamationstidens längd bedöms vara omkring sex månader vid komplexa immateriella tjänster av det mera avancerade slaget, såsom juridisk rådgivning, och någon månad kortare vid något mindre avancerade tjänster, såsom undersökning av fastigheter. Detta gäller i princip oavsett partsförhållandena och är att ses som huvudregler. En sammanvägd bedömning av omständigheterna ska göras för att bestämma reklamationsfristens längd i det enskilda fallet. Avslutningsvis presenteras, de lege ferenda, ett förslag på en förtydligad och modifierad rättslig reglering, där det understryks att reklamationsplikten gäller vid alla former av avtalsbrott och att preklusion är rättsföljden vid reklamationsförsummelse enligt huvudregeln. Detta kompenseras med en mindre ingripande alternativregel som kan ti

Torque teno virus (TTV) is a group of chronically persisting viruses with a short circular DNA genome. TTV demonstrates a wide sequence diversity and a large majority of humans are chronically infected by one or more types of TTV. As TTV is ubiquitous, and viral replication correlates with immune status, TTV has been studied as a marker to assess global functional immune competence in transplant recipients. Most studies of the prevalence, amounts, and variation in TTV have been performed using PCR assays. We here present a comparison of the most frequently used quantitative PCR (qPCR) assay for TTV with shotgun metagenomic sequencing for detection and characterization of TTV in a cohort of pediatric cancer patients. The results show that TTV is more common than the qPCR assays indicate, and analysis of the TTV genome sequences indicate that a qPCR with primers and probe designed on a conserved region of the TTV genome may fail to detect some of the TTV strains found in this study., Last two authors: Ljungman G and Andersson B contributed equally

Torque teno virus (TTV) is a group of chronically persisting viruses with a short circular DNA genome. TTV demonstrates a wide sequence diversity and a large majority of humans are chronically infected by one or more types of TTV. As TTV is ubiquitous, and viral replication correlates with immune status, TTV has been studied as a marker to assess global functional immune competence in transplant recipients. Most studies of the prevalence, amounts, and variation in TTV have been performed using PCR assays. We here present a comparison of the most frequently used quantitative PCR (qPCR) assay for TTV with shotgun metagenomic sequencing for detection and characterization of TTV in a cohort of pediatric cancer patients. The results show that TTV is more common than the qPCR assays indicate, and analysis of the TTV genome sequences indicate that a qPCR with primers and probe designed on a conserved region of the TTV genome may fail to detect some of the TTV strains found in this study., Last two authors: Ljungman G and Andersson B contributed equally

Torque teno virus (TTV) is a group of chronically persisting viruses with a short circular DNA genome. TTV demonstrates a wide sequence diversity and a large majority of humans are chronically infected by one or more types of TTV. As TTV is ubiquitous, and viral replication correlates with immune status, TTV has been studied as a marker to assess global functional immune competence in transplant recipients. Most studies of the prevalence, amounts, and variation in TTV have been performed using PCR assays. We here present a comparison of the most frequently used quantitative PCR (qPCR) assay for TTV with shotgun metagenomic sequencing for detection and characterization of TTV in a cohort of pediatric cancer patients. The results show that TTV is more common than the qPCR assays indicate, and analysis of the TTV genome sequences indicate that a qPCR with primers and probe designed on a conserved region of the TTV genome may fail to detect some of the TTV strains found in this study., Last two authors: Ljungman G and Andersson B contributed equally

Background: Necrotizing enterocolitis (NEC) is an inflammatory bowel disease in preterm neonates with high morbidity and mortality. The only treatment available is supportive with broad-spectrum antibiotics and gastrointestinal rest. Better understanding of the pathogenesis is crucial for the development of new therapies. Vascular adhesion protein-1 (VAP-1), expressed in human blood vessels and lymphatic, plays a crucial role in the pathogenesis of inflammatory diseases in adults. The aim of the study was to investigate the VAP-1 expression in the intestines of infants affected by NEC. Methods: Intestinal tissues from 42 preterm infants with NEC were examined with immunohistochemical staining using antibodies against VAP-1 and semi-automated digital image analysis was performed to determine tissue protein expression of VAP-1 in blood vessels located in the submucosa. Intestinal tissue from 26 neonates that underwent laparotomy and ileostomy due to other intestinal surgical conditions served as controls. Clinical data and protein expression were compared between the NEC-group and Controls. Results: Mean gestational age was lower in NEC infants compared to controls, 26.6 +/- 3.0 gestational weeks versus 36.5 +/- 4.0 (p < 0.001) but without any significant difference in median postnatal age at surgery; for NEC 8 (5-27) days and for controls 3 (1-36) days (p = 0.6). Low VAP-1 correlated with increased risk for developing NEC in the logistic regression (p < 0.001). Multiple linear regression showed that both gestational age and NEC were independent predictors of VAP-1 expression. Conclusion: VAP-1 may play a role in the pathogenesis of NEC. Diminished expression of VAP-1 independent of maturation could indicate arrested vascular development in infants suffering from NEC. Further studies are needed to elucidate the role of VAP-1 in NEC.

Background: Necrotizing enterocolitis (NEC) is an inflammatory bowel disease in preterm neonates with high morbidity and mortality. The only treatment available is supportive with broad-spectrum antibiotics and gastrointestinal rest. Better understanding of the pathogenesis is crucial for the development of new therapies. Vascular adhesion protein-1 (VAP-1), expressed in human blood vessels and lymphatic, plays a crucial role in the pathogenesis of inflammatory diseases in adults. The aim of the study was to investigate the VAP-1 expression in the intestines of infants affected by NEC. Methods: Intestinal tissues from 42 preterm infants with NEC were examined with immunohistochemical staining using antibodies against VAP-1 and semi-automated digital image analysis was performed to determine tissue protein expression of VAP-1 in blood vessels located in the submucosa. Intestinal tissue from 26 neonates that underwent laparotomy and ileostomy due to other intestinal surgical conditions served as controls. Clinical data and protein expression were compared between the NEC-group and Controls. Results: Mean gestational age was lower in NEC infants compared to controls, 26.6 +/- 3.0 gestational weeks versus 36.5 +/- 4.0 (p < 0.001) but without any significant difference in median postnatal age at surgery; for NEC 8 (5-27) days and for controls 3 (1-36) days (p = 0.6). Low VAP-1 correlated with increased risk for developing NEC in the logistic regression (p < 0.001). Multiple linear regression showed that both gestational age and NEC were independent predictors of VAP-1 expression. Conclusion: VAP-1 may play a role in the pathogenesis of NEC. Diminished expression of VAP-1 independent of maturation could indicate arrested vascular development in infants suffering from NEC. Further studies are needed to elucidate the role of VAP-1 in NEC.

Background: Necrotizing enterocolitis (NEC) is an inflammatory bowel disease in preterm neonates with high morbidity and mortality. The only treatment available is supportive with broad-spectrum antibiotics and gastrointestinal rest. Better understanding of the pathogenesis is crucial for the development of new therapies. Vascular adhesion protein-1 (VAP-1), expressed in human blood vessels and lymphatic, plays a crucial role in the pathogenesis of inflammatory diseases in adults. The aim of the study was to investigate the VAP-1 expression in the intestines of infants affected by NEC. Methods: Intestinal tissues from 42 preterm infants with NEC were examined with immunohistochemical staining using antibodies against VAP-1 and semi-automated digital image analysis was performed to determine tissue protein expression of VAP-1 in blood vessels located in the submucosa. Intestinal tissue from 26 neonates that underwent laparotomy and ileostomy due to other intestinal surgical conditions served as controls. Clinical data and protein expression were compared between the NEC-group and Controls. Results: Mean gestational age was lower in NEC infants compared to controls, 26.6 +/- 3.0 gestational weeks versus 36.5 +/- 4.0 (p < 0.001) but without any significant difference in median postnatal age at surgery; for NEC 8 (5-27) days and for controls 3 (1-36) days (p = 0.6). Low VAP-1 correlated with increased risk for developing NEC in the logistic regression (p < 0.001). Multiple linear regression showed that both gestational age and NEC were independent predictors of VAP-1 expression. Conclusion: VAP-1 may play a role in the pathogenesis of NEC. Diminished expression of VAP-1 independent of maturation could indicate arrested vascular development in infants suffering from NEC. Further studies are needed to elucidate the role of VAP-1 in NEC.

Background: Necrotizing enterocolitis (NEC) is an inflammatory bowel disease in preterm neonates with high morbidity and mortality. The only treatment available is supportive with broad-spectrum antibiotics and gastrointestinal rest. Better understanding of the pathogenesis is crucial for the development of new therapies. Vascular adhesion protein-1 (VAP-1), expressed in human blood vessels and lymphatic, plays a crucial role in the pathogenesis of inflammatory diseases in adults. The aim of the study was to investigate the VAP-1 expression in the intestines of infants affected by NEC. Methods: Intestinal tissues from 42 preterm infants with NEC were examined with immunohistochemical staining using antibodies against VAP-1 and semi-automated digital image analysis was performed to determine tissue protein expression of VAP-1 in blood vessels located in the submucosa. Intestinal tissue from 26 neonates that underwent laparotomy and ileostomy due to other intestinal surgical conditions served as controls. Clinical data and protein expression were compared between the NEC-group and Controls. Results: Mean gestational age was lower in NEC infants compared to controls, 26.6 +/- 3.0 gestational weeks versus 36.5 +/- 4.0 (p < 0.001) but without any significant difference in median postnatal age at surgery; for NEC 8 (5-27) days and for controls 3 (1-36) days (p = 0.6). Low VAP-1 correlated with increased risk for developing NEC in the logistic regression (p < 0.001). Multiple linear regression showed that both gestational age and NEC were independent predictors of VAP-1 expression. Conclusion: VAP-1 may play a role in the pathogenesis of NEC. Diminished expression of VAP-1 independent of maturation could indicate arrested vascular development in infants suffering from NEC. Further studies are needed to elucidate the role of VAP-1 in NEC.

Torque teno virus (TTV) is a group of chronically persisting viruses with a short circular DNA genome. TTV demonstrates a wide sequence diversity and a large majority of humans are chronically infected by one or more types of TTV. As TTV is ubiquitous, and viral replication correlates with immune status, TTV has been studied as a marker to assess global functional immune competence in transplant recipients. Most studies of the prevalence, amounts, and variation in TTV have been performed using PCR assays. We here present a comparison of the most frequently used quantitative PCR (qPCR) assay for TTV with shotgun metagenomic sequencing for detection and characterization of TTV in a cohort of pediatric cancer patients. The results show that TTV is more common than the qPCR assays indicate, and analysis of the TTV genome sequences indicate that a qPCR with primers and probe designed on a conserved region of the TTV genome may fail to detect some of the TTV strains found in this study., Last two authors: Ljungman G and Andersson B contributed equally

Formal settings of youth participation such as youth and student councils aim to educate young people into models of citizenships and mainstream politics. The activities developed in these spaces are framed in a way as to allow young people to develop learning activities that enhance their participatory skills and competences. These activities however can result in a set of unintended outcomes, where young people end up learning more than the officially recognised skills and competences. In this article, I use elements from the PARTICISPACE project to illustrate how despite the good intentions surrounding the framing of formal spaces of learning, these spaces can function as a mean for the reproduction of political models of participation that do not only fail to challenge the status quo, but in fact create the kind of citizens that enjoy the cynical and bureaucratic political participation that characterises late capitalism.

Validation of models for plant disease management is a crucial part in the development of decision support systems in plant protection. Bespoke field trials are usually conducted to determine the performance of a model under practical conditions. However, field trials are very resource-demanding, and the use of already existing field trial data could significantly reduce costs for model validation. In this study, we took this novel approach to verify the performance of models for determining the need of fungicide applications against leaf blotch diseases in wheat by utilising historical weather data and yield data available from fungicide efficacy field trials. Two models based on humidity factors were used in the study. To estimate how specific humidity settings in the two models affect the number of recommended fungicide treatments per season, historical weather data from a 5-year period from weather stations in Denmark, Sweden, Norway, Finland, and Lithuania was used. The model output shows major differences between seasons and regions, typically recommending between one and three treatments per season. To determine the prediction potential of the models, data on yield gains from either one or two fungicide applications in fungicide efficacy trials conducted in wheat over a 5-year period in the five countries was utilised. The yield responses from fungicide treatments in the efficacy trials varied considerably between years and countries, as did the proportion of predictions of profitable treatments. In general, there was a tendency for the models to overestimate the need to apply fungicides (low specificity), but they rarely failed to recommend an application that was needed (high sensitivity). Despite the importance of having specific trials across regions in order to adjust models to local cropping and weather conditions, our study shows that historical weather data and existing field trial data have the potential to be used in model validation.

Validation of models for plant disease management is a crucial part in the development of decision support systems in plant protection. Bespoke field trials are usually conducted to determine the performance of a model under practical conditions. However, field trials are very resource-demanding, and the use of already existing field trial data could significantly reduce costs for model validation. In this study, we took this novel approach to verify the performance of models for determining the need of fungicide applications against leaf blotch diseases in wheat by utilising historical weather data and yield data available from fungicide efficacy field trials. Two models based on humidity factors were used in the study. To estimate how specific humidity settings in the two models affect the number of recommended fungicide treatments per season, historical weather data from a 5-year period from weather stations in Denmark, Sweden, Norway, Finland, and Lithuania was used. The model output shows major differences between seasons and regions, typically recommending between one and three treatments per season. To determine the prediction potential of the models, data on yield gains from either one or two fungicide applications in fungicide efficacy trials conducted in wheat over a 5-year period in the five countries was utilised. The yield responses from fungicide treatments in the efficacy trials varied considerably between years and countries, as did the proportion of predictions of profitable treatments. In general, there was a tendency for the models to overestimate the need to apply fungicides (low specificity), but they rarely failed to recommend an application that was needed (high sensitivity). Despite the importance of having specific trials across regions in order to adjust models to local cropping and weather conditions, our study shows that historical weather data and existing field trial data have the potential to be used in model validation.

Background: Necrotizing enterocolitis (NEC) is an inflammatory bowel disease in preterm neonates with high morbidity and mortality. The only treatment available is supportive with broad-spectrum antibiotics and gastrointestinal rest. Better understanding of the pathogenesis is crucial for the development of new therapies. Vascular adhesion protein-1 (VAP-1), expressed in human blood vessels and lymphatic, plays a crucial role in the pathogenesis of inflammatory diseases in adults. The aim of the study was to investigate the VAP-1 expression in the intestines of infants affected by NEC. Methods: Intestinal tissues from 42 preterm infants with NEC were examined with immunohistochemical staining using antibodies against VAP-1 and semi-automated digital image analysis was performed to determine tissue protein expression of VAP-1 in blood vessels located in the submucosa. Intestinal tissue from 26 neonates that underwent laparotomy and ileostomy due to other intestinal surgical conditions served as controls. Clinical data and protein expression were compared between the NEC-group and Controls. Results: Mean gestational age was lower in NEC infants compared to controls, 26.6 +/- 3.0 gestational weeks versus 36.5 +/- 4.0 (p < 0.001) but without any significant difference in median postnatal age at surgery; for NEC 8 (5-27) days and for controls 3 (1-36) days (p = 0.6). Low VAP-1 correlated with increased risk for developing NEC in the logistic regression (p < 0.001). Multiple linear regression showed that both gestational age and NEC were independent predictors of VAP-1 expression. Conclusion: VAP-1 may play a role in the pathogenesis of NEC. Diminished expression of VAP-1 independent of maturation could indicate arrested vascular development in infants suffering from NEC. Further studies are needed to elucidate the role of VAP-1 in NEC.

This thesis devolops a general formalism for continuous feedback control in quantum systems. The main result is a quantum Fokker-Planck master equation describing the joint dynamics of a quantum system and a detector with finite bandwidth. For a fast detector, this equation can be reduced to a Markovian master equation for the system dynamics. In particular, the formalism is amenable to analytical treatments of feedback protocols that depend nonlinearly on the measured signal. Previously, only numerical methods were available for this. We apply the formalism on two toy models to highlight its usefuleness. We find that the formalism provides insight into the connection between thermodynamics and information theory.

The thesis seeks to investigate whether there is a general duty to give notice in the event of a breach of contract in situations not covered by a statutory regulation. A particular purpose is to clarify the inner nature of the legal institute of notification when it comes to contracts on complex intangible services, such as legal advice and investigation services. A legal dogmatic method is applied. Supported by case law from the Supreme Court as well as by doctrine, the conclusion is that there is indeed a general duty to give notice in the event of a breach of contract in Swedish law. At the same time, the author identifies certain ambiguities in the scope of this duty. A recent case seems to indicate that the general duty to give notice is limited to breach of contract in the strict sense. Another ambiguity is whether preclusion is the exclusive legal consequence of a failure to notify, or whether less intrusive consequences may follow. For complex intangible services, the investigation indicates that the duty to give notice starts even before actual knowledge of the breach of contract, which is surprising since there is no obligation to investigate the performance of such services in Swedish law. The length of the notification period is estimated to be around six months for advanced complex intangible services, such as legal advice, and about a month or two shorter for somewhat less advanced services, such as investigation of real estate. This is to be seen as the main rule, but a balanced assessment of the circumstances in casu must be made to determine the length of the notification period in the individual case. Finally, a proposal for a clarified and modified legal regulation is presented de lege ferenda, which emphasizes that the duty to give notice applies to all forms of breach of contract and that, as a default rule, preclusion is the legal consequence in case of a failure to notify. A less intrusive alternative rule is suggested for situations where th, Uppsatsen syftar till att utreda rättsläget i frågan om en allmän reklamationsplikt vid avtalsbrott i situationer som inte omfattas av någon lagreglering. Ett särskilt syfte är att klargöra reklamationsplikten närmare beskaffenhet när det handlar om avtal om komplexa immateriella tjänster, såsom rådgivnings- och undersökningstjänster. En rättsdogmatisk metod tillämpas. Utredningen kommer fram till att det finns en allmän reklamationsplikt vid avtalsbrott i svensk rätt. Slutsatsen stöds av rättspraxis från Högsta domstolen liksom av doktrin. Samtidigt identifierar författaren vissa oklarheter i den allmänna reklamationspliktens omfattning. Ett färskt rättsfall kan uppfattas som att den allmänna reklamationsplikten är begränsad till avtalsbrott i strikt mening. En annan oklarhet är om rättsföljden vid försummad reklamation alltid är preklusion, eller om mindre ingripande konsekvenser kan bli aktuella. Författaren gör bedömningen att det rättsliga stödet är svagt för någon annan rättsföljd än preklusion. Utredningen visar att reklamationsplikten vid komplexa immateriella tjänster startar redan före faktisk vetskap om avtalsbrottet, vilket är överraskande eftersom undersökningsplikt saknas. Reklamationstidens längd bedöms vara omkring sex månader vid komplexa immateriella tjänster av det mera avancerade slaget, såsom juridisk rådgivning, och någon månad kortare vid något mindre avancerade tjänster, såsom undersökning av fastigheter. Detta gäller i princip oavsett partsförhållandena och är att ses som huvudregler. En sammanvägd bedömning av omständigheterna ska göras för att bestämma reklamationsfristens längd i det enskilda fallet. Avslutningsvis presenteras, de lege ferenda, ett förslag på en förtydligad och modifierad rättslig reglering, där det understryks att reklamationsplikten gäller vid alla former av avtalsbrott och att preklusion är rättsföljden vid reklamationsförsummelse enligt huvudregeln. Detta kompenseras med en mindre ingripande alternativregel som kan ti

Torque teno virus (TTV) is a group of chronically persisting viruses with a short circular DNA genome. TTV demonstrates a wide sequence diversity and a large majority of humans are chronically infected by one or more types of TTV. As TTV is ubiquitous, and viral replication correlates with immune status, TTV has been studied as a marker to assess global functional immune competence in transplant recipients. Most studies of the prevalence, amounts, and variation in TTV have been performed using PCR assays. We here present a comparison of the most frequently used quantitative PCR (qPCR) assay for TTV with shotgun metagenomic sequencing for detection and characterization of TTV in a cohort of pediatric cancer patients. The results show that TTV is more common than the qPCR assays indicate, and analysis of the TTV genome sequences indicate that a qPCR with primers and probe designed on a conserved region of the TTV genome may fail to detect some of the TTV strains found in this study., Last two authors: Ljungman G and Andersson B contributed equally

Caloric need has long been thought a major driver of appetite. However, it is unclear whether caloric need regulates appetite in environments offered by many societies today where there is no shortage of food. Here we observed that wildtype mice with free access to food did not match calorie intake to calorie expenditure. While the size of a meal affected subsequent intake, there was no compensation for earlier under- or over-consumption. To test how spontaneous eating is subject to caloric control, we manipulated O-linked β-N-acetylglucosamine (O-GlcNAc), an energy signal inside cells dependent on nutrient access and metabolic hormones. Genetic and pharmacological manipulation in mice increasing or decreasing O-GlcNAcylation regulated daily intake by controlling meal size. Meal size was affected at least in part due to faster eating speed. Without affecting meal frequency, O-GlcNAc disrupted the effect of caloric consumption on future intake. Across days, energy balance was improved upon increased O-GlcNAc levels and impaired upon removal of O-GlcNAcylation. Rather than affecting a perceived need for calories, O-GlcNAc regulates how a meal affects future intake, suggesting that O-GlcNAc mediates a caloric memory and subsequently energy balance.