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The aim of the article is to explore the tensions and dilemmas that arise when bottom-up projects involving young people are placed within policy- and administratively driven institutions. The tensions and dilemmas are illustrated through three cases. The first case illustrates the colliding interests that can arise when institutions seem unable to create space for ideas from youth projects, while the second shows how bottom-up work is subordinated to policy priorities and high-level management anxieties. The third case illustrates the difficulties that arise when youth projects aiming at doing transformative and educative work collide with formal mechanisms of the legal system. The tensions and dilemmas at play are analysed through the concepts of disciplinary and project logic. The article concludes with a discussion of power relations, ownership, and control connected to youth projects and participation.

Climate is assumed to strongly influence species distribution and abundance. Although the performance of many organisms is influenced by the climate in their immediate proximity, the climate data used to model their distributions often have a coarse spatial resolution. This is problematic because the local climate experienced by individuals might deviate substantially from the regional average. This problem is likely to be particularly important for sessile organisms like plants and in environments where small-scale variation in climate is large. To quantify the effect of local temperature on vital rates and population growth rates, we used temperature values measured at the local scale (in situ logger measures) and integral projection models with demographic data from 37 populations of the forest herb Lathyrus vernus across a wide latitudinal gradient in Sweden. To assess how the spatial resolution of temperature data influences assessments of climate effects, we compared effects from models using local data with models using regionally aggregated temperature data at several spatial resolutions (≥1 km). Using local temperature data, we found that spring frost reduced the asymptotic population growth rate in the first of two annual transitions and influenced survival in both transitions. Only one of the four regional estimates showed a similar negative effect of spring frost on population growth rate. Our results for a perennial forest herb show that analyses using regionally aggregated data often fail to identify the effects of climate on population dynamics. This emphasizes the importance of using organism-relevant estimates of climate when examining effects on individual performance and population dynamics, as well as when modeling species distributions. For sessile organisms that experience the environment over small spatial scales, this will require climate data at high spatial resolutions.

The aim of the article is to explore the tensions and dilemmas that arise when bottom-up projects involving young people are placed within policy- and administratively driven institutions. The tensions and dilemmas are illustrated through three cases. The first case illustrates the colliding interests that can arise when institutions seem unable to create space for ideas from youth projects, while the second shows how bottom-up work is subordinated to policy priorities and high-level management anxieties. The third case illustrates the difficulties that arise when youth projects aiming at doing transformative and educative work collide with formal mechanisms of the legal system. The tensions and dilemmas at play are analysed through the concepts of disciplinary and project logic. The article concludes with a discussion of power relations, ownership, and control connected to youth projects and participation.

This project investigates the unintended effects and consequences within the sugarcane-bioethanol value chain in Brazil using the SEI-PCS method. The project traces four sustainability metrics – water use, land use, CO2 emissions and working conditions – and the value chain’s impact on these at the places of origin. The analysis is supported by visualizations illustrating the flow and spatial extent of the value chain, heavily relying on data from production, processing, trade, and export from three companies. SEI-PCS is an effective method for gaining a quick overview of the value chain’s segments and impact. However, its dependence on granular data limits its applicability. While it can identify the impact, understanding their underlying causes remains challenging. Despite the limitations, the project demonstrates the method’s potential to enhance traceability and identify impacts, which is particularly relevant for the growing bioethanol market to ensure a green transition.

Denne opgave tager udgangspunkt i problemstillingen om, hvorvidt ekstensive græsningsregimer i samtænkning med vildtforvaltning kan optimere plejen i Naturnationalpark Hanstholm, og hvordan disse kan virke understøttende for økosystemfunktioner og habitater. Opgavens overordnet problem, er i hvilken grad baggrundsgræsning af kronvildtet har betydning for plejen af Hanstholm Vildtreservat, og i hvilken grad baggrundsgræsningen kan optimeres og understøttes. Derudover redegøres for relevante metodiske- og videnskabsteoretiske overvejelser, samt for relevant data, teori og litteraturreviews, som danner baggrunden for analysen. Analysen undersøger ud fra eksklusion- og inklusion af ekstensive græssere, hvilke konkrete forvaltningsforslag der bør stilles. Herudover undersøges forvaltningen af kronvildtet og dennes betydning i en adfærds- og bestandsregulerende kontekst. Opgavens hovedformål er, at findes det bedst mulige forslag til forvaltning gennem optimering og inklusion af baggrundsgræsning af kronvildt. Der drages perspektiverer til, i hvilken grad open-ended naturforvaltning er mulig, samt i hvilken grad lovgivning og samtid er begrænsende for optimal naturpleje, samt for økosystemer- og deres funktioner. Konklusionen finder, at kronvildtet har betydelige økosystemfunktioner, og hvorfor en samtænkning af et ekstensivt græsningsregime, og forvaltning af kronvildt, vil virke understøttende for hinanden, og bidrage til bevarelse af sårbare atlantiske habitatnaturtyper., This thesis is based on the issue of whether extensive grazing regimes, in conjunction with wildlife management, can optimize nature preservation in Naturnationalpark Hanstholm, and how these can support ecosystem functions and habitats. The main problem of the thesis is to what extent background grazing by red deer affects the maintenance of Hanstholm Wildlife Reserve, and to what extent this background grazing can be optimized and supported. Additionally, relevant methodological and scientific theoretical considerations are discussed, as well as relevant data, theory, and literature reviews that form the basis for the analysis. The analysis investigates, based on the exclusion and inclusion of extensive grazers, which specific management proposals should be made. Furthermore, the management of red deer and its significance in a behavioral and population-regulating context are examined. The main purpose of the thesis is to find the best possible management proposal through the optimization and inclusion of background grazing by red deer. Perspectives are drawn on the extent to which open-ended nature management is possible, and to what extent regulations and sociecologial factors are limiting for optimal nature preservation, as well as for ecosystems and their functions. The conclusion finds that red deer have significant ecosystem functions, and why a combination of an extensive grazing regime and red deer management will support each other and contribute to the preservation of vulnerable Atlantic habitat types.

English abstract: The reception of Arvo Pärt’s religiously rooted tintinnabuli works have been wide and multifaceted. Grounded in a specific religious tradition, the Russian orthodox church, it can seem paradoxical that this music has been embraced both in the context of popular music culture, as well as in New Age settings to such a large extent, that the composer has been somewhat regarded as a popular music idol. Main themes in the academic research around these works have predominantly focused on the relationship between the works and Pärt’s religious belief, the connection between tintinnabuli and secular spirituality, while others have focused on Pärt’s reception in popular culture. This thesis, however, examines how the seemingly paradoxical, diverse, and multifaceted reception of Arvo Pärt’s religiously rooted tintinnabuli works can be understood. In other words, this thesis asks the question, of how these seemingly incongruous narratives are able exist side by side. The focal point of this investigation is Pärt’s work Te Deum (1985/1992/2007), which serves as the primary example throughout the thesis. To address this question, this thesis sets out by examining in what ways Te Deum can be perceived as a product of Pärt’s religious belief and theological reflections. Following this, the second part of the thesis is dedicated to exploring the prevalent trends in the reception, concerning themes such as tintinnabuli as music therapy, as a critique of society, the perceived spiritual demeanor of the composer, as well as the connection to American minimalism and film music. Additionally, the implication of any connection between tintinnabuli and the serialist composers from the aftermath of World War II will also be discussed. As the second part deals with narratives both connected to popular cultural phenomena, as well as narratives emanating from New Age-contexts, this part is mainly based on the theoretical foundation of Charles Taylors book A Secular Age

Denne opgave tager udgangspunkt i problemstillingen om, hvorvidt ekstensive græsningsregimer i samtænkning med vildtforvaltning kan optimere plejen i Naturnationalpark Hanstholm, og hvordan disse kan virke understøttende for økosystemfunktioner og habitater. Opgavens overordnet problem, er i hvilken grad baggrundsgræsning af kronvildtet har betydning for plejen af Hanstholm Vildtreservat, og i hvilken grad baggrundsgræsningen kan optimeres og understøttes. Derudover redegøres for relevante metodiske- og videnskabsteoretiske overvejelser, samt for relevant data, teori og litteraturreviews, som danner baggrunden for analysen. Analysen undersøger ud fra eksklusion- og inklusion af ekstensive græssere, hvilke konkrete forvaltningsforslag der bør stilles. Herudover undersøges forvaltningen af kronvildtet og dennes betydning i en adfærds- og bestandsregulerende kontekst. Opgavens hovedformål er, at findes det bedst mulige forslag til forvaltning gennem optimering og inklusion af baggrundsgræsning af kronvildt. Der drages perspektiverer til, i hvilken grad open-ended naturforvaltning er mulig, samt i hvilken grad lovgivning og samtid er begrænsende for optimal naturpleje, samt for økosystemer- og deres funktioner. Konklusionen finder, at kronvildtet har betydelige økosystemfunktioner, og hvorfor en samtænkning af et ekstensivt græsningsregime, og forvaltning af kronvildt, vil virke understøttende for hinanden, og bidrage til bevarelse af sårbare atlantiske habitatnaturtyper., This thesis is based on the issue of whether extensive grazing regimes, in conjunction with wildlife management, can optimize nature preservation in Naturnationalpark Hanstholm, and how these can support ecosystem functions and habitats. The main problem of the thesis is to what extent background grazing by red deer affects the maintenance of Hanstholm Wildlife Reserve, and to what extent this background grazing can be optimized and supported. Additionally, relevant methodological and scientific theoretical considerations are discussed, as well as relevant data, theory, and literature reviews that form the basis for the analysis. The analysis investigates, based on the exclusion and inclusion of extensive grazers, which specific management proposals should be made. Furthermore, the management of red deer and its significance in a behavioral and population-regulating context are examined. The main purpose of the thesis is to find the best possible management proposal through the optimization and inclusion of background grazing by red deer. Perspectives are drawn on the extent to which open-ended nature management is possible, and to what extent regulations and sociecologial factors are limiting for optimal nature preservation, as well as for ecosystems and their functions. The conclusion finds that red deer have significant ecosystem functions, and why a combination of an extensive grazing regime and red deer management will support each other and contribute to the preservation of vulnerable Atlantic habitat types.

This project investigates the unintended effects and consequences within the sugarcane-bioethanol value chain in Brazil using the SEI-PCS method. The project traces four sustainability metrics – water use, land use, CO2 emissions and working conditions – and the value chain’s impact on these at the places of origin. The analysis is supported by visualizations illustrating the flow and spatial extent of the value chain, heavily relying on data from production, processing, trade, and export from three companies. SEI-PCS is an effective method for gaining a quick overview of the value chain’s segments and impact. However, its dependence on granular data limits its applicability. While it can identify the impact, understanding their underlying causes remains challenging. Despite the limitations, the project demonstrates the method’s potential to enhance traceability and identify impacts, which is particularly relevant for the growing bioethanol market to ensure a green transition.

English abstract: The reception of Arvo Pärt’s religiously rooted tintinnabuli works have been wide and multifaceted. Grounded in a specific religious tradition, the Russian orthodox church, it can seem paradoxical that this music has been embraced both in the context of popular music culture, as well as in New Age settings to such a large extent, that the composer has been somewhat regarded as a popular music idol. Main themes in the academic research around these works have predominantly focused on the relationship between the works and Pärt’s religious belief, the connection between tintinnabuli and secular spirituality, while others have focused on Pärt’s reception in popular culture. This thesis, however, examines how the seemingly paradoxical, diverse, and multifaceted reception of Arvo Pärt’s religiously rooted tintinnabuli works can be understood. In other words, this thesis asks the question, of how these seemingly incongruous narratives are able exist side by side. The focal point of this investigation is Pärt’s work Te Deum (1985/1992/2007), which serves as the primary example throughout the thesis. To address this question, this thesis sets out by examining in what ways Te Deum can be perceived as a product of Pärt’s religious belief and theological reflections. Following this, the second part of the thesis is dedicated to exploring the prevalent trends in the reception, concerning themes such as tintinnabuli as music therapy, as a critique of society, the perceived spiritual demeanor of the composer, as well as the connection to American minimalism and film music. Additionally, the implication of any connection between tintinnabuli and the serialist composers from the aftermath of World War II will also be discussed. As the second part deals with narratives both connected to popular cultural phenomena, as well as narratives emanating from New Age-contexts, this part is mainly based on the theoretical foundation of Charles Taylors book A Secular Age

A significant amount of bacteria in the urine can be found in dogs with urinary tract infections (UTIs), as well as in dogs with subclinical bacteriuria (SBU). The inflammatory cytokines interleukin (IL)-6, -8 and -10 play an important role in response to bacterial colonization of the urinary tract, and thus it is expected to find higher levels of the interleukins aforementioned in relation to significant bacteriuria. The aim of this study was to investigate urinary IL-6, -8 and -10 in dogs with and without significant bacteriuria as a step in solving the question of why there is a difference in host immune response between cases of UTIs compared to cases of SBU. This study was designed as a prospective cross-sectional study and included 82 urine specimens from 53 dogs that were divided into four study groups: Pyelonephritis, cystitis, SBU and controls. Urine specimens were analyzed for urinary IL-6, -8 and -10 using canine-specific sandwich- ELISAs proprietary to each interleukin and comparisons were made between and within the groups, as well as analyzed for any correlations with pyuria and urine specific gravity (USG). Prior to the specimen analyses, the assays were optimized in effort to establish the most optimal protocol for testing on canine urine specimens. IL-8 was found significantly higher in dogs with bacteriuria compared to those without, although no significant difference could be found between the individual bacteriuria groups. Additionally, IL-8 was significantly higher in urine specimens with moderate and pronounced pyuria, and USG was found to decrease with severity of urinary disease. IL-6 and IL-10 were not detected in the urine specimens included for this study. In summary, IL-8 may be a potential biomarker in relation to urinary conditions such as SBU, cystitis and pyelonephritis.

Aim: There is increasing interest in open-ended restoration with the focus on restoring natural processes rather than static compositional goals. Here, we investigated vegetation dynamics in response to three decades of trophic rewilding with large herbivores in a recent anthropogenic, fertile 55-km2 landscape on reclaimed marine sediments. This site provides important insights into plant community assembly in rewilded, young ecosystems. Location: Oostvaardersplassen, the Netherlands. Methods: Using field surveys and vegetation data spanning two decades, we investigate vegetation dynamics of the mesic grasslands in Oostvaardersplassen, a pioneer trophic rewilding site in the Netherlands. To identify the effects of grazing and other ecological processes, we include comparisons to an adjacent ungrazed control site and to the dark diversity, that is, missing species expected to be present given the environment and geography. Results: The impact of large herbivores has led to a more open and homogenous vegetation with higher plant species richness in the mesic grasslands of Oostvaardersplassen compared to the ungrazed control. Compared to species in the dark diversity, the species present are more common in the region, more stress-tolerant, and less competitive, in line with joint effects of grazing and immigrational lag. Conclusions: The changes in vegetation composition and structure show that rewilding with large herbivores promotes the prevalence of stress-tolerant and low-statured plant species, which are in decline in the broader landscape while reducing the dominance of otherwise widespread, competition-adapted species. The absence of numerous rare species suggests that dispersal limitation poses an important constraint for the diversity build-up in anthropogenically isolated natural areas, necessitating active species introductions to mitigate this issue in the short to medium term.

Whole-plant senescence, defined as a decrease in individual fitness as an organism grows older, has often been assumed to not occur in plants; however, it has now been detected in a range of plant taxa. Still, reported senescence patterns vary substantially, and it remains unknown how consistent patterns are within phylogenetic groups and how they may be affected by environmental factors. Plants show a high diversity in life-history traits within phylogenetic groups and environments, but shared traits among related species are also common, making both diverse and similar patterns probable. Here, we explore how mortality changes with advancing age in four closely related species (Dactylorhiza incarnata, D. lapponica, D. maculata and Gymnadenia conopsea) across two sites in Norway: the coastal Nordmarka and inland Sølendet. Using data collected over 34 years, following more than 2500 individual plants, we conduct Bayesian survival trajectory analysis to assess mortality age trajectories. A simple Weibull model, illustrating increasing mortality at a decelerating rate with age, was the best fit for all species at both sites. From these models, we calculate rates of senescence and compare them using Kullback–Leibler divergences, finding no notable differences in rates between species or sites. Synthesis. Our findings suggest that actuarial senescence, an increase in mortality with advancing age, may be common in orchids and show that demographic ageing can proceed similarly in closely related taxa across different environments.

Dette specialeprojekt havde til formål at vurdere, hvordan tid siden sidste vaccination (TSLV), alder og vægt påvirker antistofniveauerne af canine parvovirus (CPV-2), distemper virus (CDV) og adenovirus (CAV) ved at bruge den serologiske patientnære (in-house) antistoftiter-test, VacciCheck®, til at måle antistofniveauer i en population af danske hunde. Studiet inkluderede prøver fra 166 hunde med en kendt sidste vaccinationsdato. Hundene skulle enten være ≳ seks måneder gamle og vaccineret mindst én gang med en modificeret levende kombinationsvaccine mod CDV, CAV og CPV-2 (DHP) inden for seks-måneders-alderen, men ikke revaccineret siden, eller voksne hunde sidst vaccineret ≳ tre år tidligere. De blev kategoriseret i definerede grupper baseret på TSLV, alder og vægt. Prøverne blev analyseret for beskyttende antistoftitre (PATs) defineret som ≥ 1:80 for CPV-2, ≥ 1:32 for CDV og ≥ 1:16 for CAV. Andelen af hunde med PATs var 98,8% for CPV-2, 76,5% for CDV og 88,0% for CAV. Med hensyn til TSLV, var der en generel forskel i CPV-2’s og CAV’s antistofniveauer mellem grupperne samt en svag negativ korrelation mellem TSLV og CPV-2. Alder viste en generel forskel i CPV-2 antistofniveauer mellem grupperne og en moderat negativ korrelation mellem alder og CPV-2 samt en svag negativ korrelation for CAV. Derudover havde vægt og CPV-2 også en svag negativ korrelation. På trods af resultaterne, som indikerer en sammenhæng mellem en stigning i disse tre faktorer og et fald i CPV-2 antistofniveauer samt en tendens til at CAV antistofniveauet falder med stigende TSLV og alder, konkluderes det stadig, at udviklingen og opretholdelsen af antistofniveau efter vaccination er meget individuel og afhænger af forskellige andre faktorer, som påvirker denne proces. Selvom flertallet af de inkluderede hunde opretholder PATs i mere end tre år, manglede 15 (11.2%) ud af 134 hunde over ét år PATs for én eller to sygdomme og havde en TSLV på ≤ tre år. Af de 32 juvenile hunde manglede 9 (28.1%) PA, This master’s thesis aimed to assess the influence of time since last vaccination (TSLV), age, and weight on antibody titre levels, by utilising the serological in-house antibody titre test, VacciCheck®, to measure antibody titres against canine parvovirus (CPV-2), distemper virus (CDV), and adenovirus (CAV) in a population of Danish dogs. The study included samples from 166 dogs with a known last date of vaccination. They were required to be either aged ≳ six months and vaccinated at least once with a modified live combination vaccine against CDV, CAV, and CPV-2 (DHP) before six months of age but not revaccinated since, or adult dogs last vaccinated ≳ three years prior to presentation. The dogs were categorised into defined groups based on TSLV, age, and weight. Samples were analysed for protective antibody titres (PAT) defined as ≥ 1:80 for CPV-2, ≥ 1:32 for CDV, and ≥ 1:16 for CAV. The percentage of dogs with PATs was 98.8% for CPV-2, 76.5% for CDV, and 88.0% for CAV. In terms of TSLV, an overall difference for CPV-2 and CAV antibody titres was observed between the groups as well as a weak negative correlation between TSLV and CPV-2. Age demonstrated an overall difference in CPV-2 antibody titres among groups and a moderate negative correlation between age and CPV-2 as well as a weak negative correlation for CAV. Additionally, weight and CPV-2 also had a weak negative correlation. Despite the results indicating that as these three factors increase, the CPV-2 antibody titres decrease, and that there is a tendency for CAV antibody titres to decrease with increasing TSLV and age, it is still concluded that the development and the longevity of antibodies following vaccination are highly individualised for each dog and dependent on various other factors that influence this process. Though the majority of the included dogs maintained a PAT for more than three years, 15 (11.2%) out of 134 dogs over one year of age lacked PATs for one or two diseases and had a TSLV ≤ thr

Hovedformålet med projektet var at kortlægge prævalensen af halelæsioner hos Holstein og Holstein krydsninger i hhv. udvalgte besætninger i Nordjylland, og på et Nordjysk kreaturslagteri. Derudover skulle læsionerne beskrives makroskopisk og histologisk. Der er foretaget to delundersøgelser: en på slagteriet, hvor 457 malkekøer indgik, og her blev der fundet en prævalens på 23% [21,6%-25,2%], samt en i 16 udvalgte besætninger med i alt 2099 malkekøer, hvor prævalensen var 25% [23,6%-27,4%]. Halelæsioner fra slagteriet blev udtaget til histologisk undersøgelse. Udgangspunktet for specialet var læsioner klassificeret i tre makroskopiske grupper: 1. Akut, 2. Kronisk, 3. Ophelet. De histologiske resultater viste, at ingen akutte læsioner var akutte, selvom de makroskopisk var beskrevet sådan. Resultaterne for de kroniske læsioner viste som forventet tegn på inflammation og reparation. For de makroskopisk klassificerede ophelede læsioner viste det sig, at hårfolikler og svedkirtler var intakte, med ophobning af kollagen omkring. Udfra disse resultater kunne man ikke sige om læsionerne startede eller sluttede med denne gruppe. Af denne grund blev gruppe 3. omdøbt til i stedet at hedde ”bindevævsringe”. Det blev observeret, at læsionerne altid sad mellem 2 og 22 cm fra halespidsen, med en gennemsnitsplacering på henholdsvis 8 og 7 cm fra halespidsen for de kroniske læsioner og bindevævsringene fra slagteridelundersøgelsen, og tilsvarende henholdsvis 7 og 6,25 cm fra halespidsen i besætningsdelundersøgelsen. Læsionerne omkranser halen i varierende grad, og i størstedelen af tilfældene er omkring halvdelen af halens omkreds dækket af læsionen. Læsionen fandtes altid dorsalt på halen, hvis ikke den var fuld circumciderende. Udvalgte variabler er undersøgt i forbindelse med de to delundersøgelser. Der er udarbejdet en univariabel og multivariabel analyse på disse. Resultaterne viste en sammenhæng mellem forekomsten af halelæsioner og stig, The purpose of this master’s thesis was to estimate the prevalence of tail lesions in Danish Holstein and Holstein-mix dairy cows. The study was split in two parts, one of which occurred in selected herds, and the other at a cattle abattoir, both in Northern Jutland, Denmark. The tail lesions were described macroscopically and histologically. A sample size of 457 dairy cows in the abattoir dataset found a prevalence of tail lesions at 23% [21,6%-25,2%], whereas in the 16 studied herds with a sample size of 2099 dairy cows, a prevalence of 25% [23,6%-27,4%] was found. Tail lesions found at the abattoir were selected and stored for later histology. Lesions were categorized macroscopically into three categories, acute, chronic, and healed lesions. Histological results suggested, that despite lesions being macroscopically assessed as acute, no histological indicators of this were found. Results from chronic lesions were as expected, with signs of inflammation and reparation. Healed lesions were found to have intact hair follicles and sweat glands, with a buildup of collagen around the named structures. From these results, it cannot be concluded if the lesion arose or ended in this specific group. Therefore, Group 3 was renamed “connective tissue rings”. It was observed that lesions were always placed between 2 to 22cm from tail tip, with an average placement of 8 and 7 cm from the tip of the tail of the chronic lesions and the connective tissue rings from the abattoir data, respectively. The average location in the herd data where 7 and 6,25 cm from the tip of the tail, respectively. The lesions circumcised the tail to a varying degree, but in most cases circumcised half of the tail’s circumference. Besides the characteristic placement and distribution, it was found, that the lesions always initially arose on the dorsal surface of the tail. Selected variables were studied, in both datasets, where a univariable and multivariable analyses were

Kabuki syndrom er en sjælden neuroudviklingsforstyrrelse der rammer ca. 1:32,000-86,000 om året. Kabuki syndrom kan give svære følgevirkninger som udviklingshæmning, mental retardering, medfødt hjertemisdannelse, medfødt muskelslaphed, m.fl. samt karakteristiske ansigts-træk, der har givet navn til syndromet fra det traditionelle japanske ”Kabuki” teater. Kabuki syndrom skyldes oftest en genetisk variant i histonmethyleringsgenet KMT2D og diagnosticeres ved hjælp af genetisk sekventering, hvor kun omkring halvdelen af de sjældne genetiske sygdomme får identificeret en patogen variant. Denne afhandling foreligger de overordnede resultater ved litteratursøgning omhandlende brug af DNA methyleringssignatur, også kaldet episignatur, som en supplerende diagnostisk metode for Kabuki syndrom. DNA methyleringssignatur er et bestemt mønster af methylerede områder på genomet, der er specifikke for især sygdomme med defekte gener, der regulerer kromatin modificering, som Kabuki syndrom. Ved at sammenligne en patients methyleringsprofil med etablerede profiler af kendte genetiske sygdomme, kan man afgøre om patienten matcher sygdomsprofilen. Ud fra artiklerne kan det udledes, at DNA methyleringssignatur har mange fordele ved diagnosticering af Kabuki syndrom. Fra at diagnosticeringsraten i flere studier kunne øges, til at adskille Kabuki syndrom fra andre klinisk overlappende syndromer, diagnosticere mosaicisme, samt kunne re-klassificere varianter med ukendt betydning. Derudover var det klart at fordelene især gavnede patienter, hvor der ikke kunne findes en diagnose ved genetisk sekventering eller ved tvivl om den kliniske diagnose eller varianternes betydning., Kabuki syndrome is a rare neurodevelopmental disorder that affects approximately 1 in 32,000-86,000births annually. Kabuki syndrome can result in severe consequences such as developmental delay, mental retardation, congenital heart defects, congenital muscle hypotonia, and more. It is characterized by distinctive facial features, which inspired the syndrome's name from the traditional Japanese "Kabuki" theater. The syndrome is most commonly caused by a genetic variant in the histone methylation gene KMT2D, and diagnosis is typically done through genetic sequencing. However, only about half of rare genetic diseases can be identified with a pathogenic variant using this method. This thesis presents the overarching results of a literature review on the use of DNA methylation signature, also known as episignature, as a complementary diagnostic method for Kabuki syndrome. DNA methylation signature is a specific pattern of methylated regions on the genome, particularly associated with diseases involving defective genes that regulate chromatin modification, such as Kabuki syndrome. By comparing a patient's methylation profile with established profiles of known genetic diseases, one can determine whether the patient matches the disease profile. The articles suggest that DNA methylation signature has several advantages in diagnosing Kabuki syndrome. It can increase the diagnostic rate in multiple studies, differentiate Kabuki syndrome from other clinically overlapping syndromes, diagnose mosaicism, and reclassify variants of unknown significance. Furthermore, it is evident that these benefits are particularly valuable for patients for whom a diagnosis could not be found through genetic sequencing or in cases of uncertainty regarding the clinical diagnosis or the significance of variants.

Kabuki syndrom er en sjælden neuroudviklingsforstyrrelse der rammer ca. 1:32,000-86,000 om året. Kabuki syndrom kan give svære følgevirkninger som udviklingshæmning, mental retardering, medfødt hjertemisdannelse, medfødt muskelslaphed, m.fl. samt karakteristiske ansigts-træk, der har givet navn til syndromet fra det traditionelle japanske ”Kabuki” teater. Kabuki syndrom skyldes oftest en genetisk variant i histonmethyleringsgenet KMT2D og diagnosticeres ved hjælp af genetisk sekventering, hvor kun omkring halvdelen af de sjældne genetiske sygdomme får identificeret en patogen variant. Denne afhandling foreligger de overordnede resultater ved litteratursøgning omhandlende brug af DNA methyleringssignatur, også kaldet episignatur, som en supplerende diagnostisk metode for Kabuki syndrom. DNA methyleringssignatur er et bestemt mønster af methylerede områder på genomet, der er specifikke for især sygdomme med defekte gener, der regulerer kromatin modificering, som Kabuki syndrom. Ved at sammenligne en patients methyleringsprofil med etablerede profiler af kendte genetiske sygdomme, kan man afgøre om patienten matcher sygdomsprofilen. Ud fra artiklerne kan det udledes, at DNA methyleringssignatur har mange fordele ved diagnosticering af Kabuki syndrom. Fra at diagnosticeringsraten i flere studier kunne øges, til at adskille Kabuki syndrom fra andre klinisk overlappende syndromer, diagnosticere mosaicisme, samt kunne re-klassificere varianter med ukendt betydning. Derudover var det klart at fordelene især gavnede patienter, hvor der ikke kunne findes en diagnose ved genetisk sekventering eller ved tvivl om den kliniske diagnose eller varianternes betydning., Kabuki syndrome is a rare neurodevelopmental disorder that affects approximately 1 in 32,000-86,000births annually. Kabuki syndrome can result in severe consequences such as developmental delay, mental retardation, congenital heart defects, congenital muscle hypotonia, and more. It is characterized by distinctive facial features, which inspired the syndrome's name from the traditional Japanese "Kabuki" theater. The syndrome is most commonly caused by a genetic variant in the histone methylation gene KMT2D, and diagnosis is typically done through genetic sequencing. However, only about half of rare genetic diseases can be identified with a pathogenic variant using this method. This thesis presents the overarching results of a literature review on the use of DNA methylation signature, also known as episignature, as a complementary diagnostic method for Kabuki syndrome. DNA methylation signature is a specific pattern of methylated regions on the genome, particularly associated with diseases involving defective genes that regulate chromatin modification, such as Kabuki syndrome. By comparing a patient's methylation profile with established profiles of known genetic diseases, one can determine whether the patient matches the disease profile. The articles suggest that DNA methylation signature has several advantages in diagnosing Kabuki syndrome. It can increase the diagnostic rate in multiple studies, differentiate Kabuki syndrome from other clinically overlapping syndromes, diagnose mosaicism, and reclassify variants of unknown significance. Furthermore, it is evident that these benefits are particularly valuable for patients for whom a diagnosis could not be found through genetic sequencing or in cases of uncertainty regarding the clinical diagnosis or the significance of variants.

Hovedformålet med projektet var at kortlægge prævalensen af halelæsioner hos Holstein og Holstein krydsninger i hhv. udvalgte besætninger i Nordjylland, og på et Nordjysk kreaturslagteri. Derudover skulle læsionerne beskrives makroskopisk og histologisk. Der er foretaget to delundersøgelser: en på slagteriet, hvor 457 malkekøer indgik, og her blev der fundet en prævalens på 23% [21,6%-25,2%], samt en i 16 udvalgte besætninger med i alt 2099 malkekøer, hvor prævalensen var 25% [23,6%-27,4%]. Halelæsioner fra slagteriet blev udtaget til histologisk undersøgelse. Udgangspunktet for specialet var læsioner klassificeret i tre makroskopiske grupper: 1. Akut, 2. Kronisk, 3. Ophelet. De histologiske resultater viste, at ingen akutte læsioner var akutte, selvom de makroskopisk var beskrevet sådan. Resultaterne for de kroniske læsioner viste som forventet tegn på inflammation og reparation. For de makroskopisk klassificerede ophelede læsioner viste det sig, at hårfolikler og svedkirtler var intakte, med ophobning af kollagen omkring. Udfra disse resultater kunne man ikke sige om læsionerne startede eller sluttede med denne gruppe. Af denne grund blev gruppe 3. omdøbt til i stedet at hedde ”bindevævsringe”. Det blev observeret, at læsionerne altid sad mellem 2 og 22 cm fra halespidsen, med en gennemsnitsplacering på henholdsvis 8 og 7 cm fra halespidsen for de kroniske læsioner og bindevævsringene fra slagteridelundersøgelsen, og tilsvarende henholdsvis 7 og 6,25 cm fra halespidsen i besætningsdelundersøgelsen. Læsionerne omkranser halen i varierende grad, og i størstedelen af tilfældene er omkring halvdelen af halens omkreds dækket af læsionen. Læsionen fandtes altid dorsalt på halen, hvis ikke den var fuld circumciderende. Udvalgte variabler er undersøgt i forbindelse med de to delundersøgelser. Der er udarbejdet en univariabel og multivariabel analyse på disse. Resultaterne viste en sammenhæng mellem forekomsten af halelæsioner og stig, The purpose of this master’s thesis was to estimate the prevalence of tail lesions in Danish Holstein and Holstein-mix dairy cows. The study was split in two parts, one of which occurred in selected herds, and the other at a cattle abattoir, both in Northern Jutland, Denmark. The tail lesions were described macroscopically and histologically. A sample size of 457 dairy cows in the abattoir dataset found a prevalence of tail lesions at 23% [21,6%-25,2%], whereas in the 16 studied herds with a sample size of 2099 dairy cows, a prevalence of 25% [23,6%-27,4%] was found. Tail lesions found at the abattoir were selected and stored for later histology. Lesions were categorized macroscopically into three categories, acute, chronic, and healed lesions. Histological results suggested, that despite lesions being macroscopically assessed as acute, no histological indicators of this were found. Results from chronic lesions were as expected, with signs of inflammation and reparation. Healed lesions were found to have intact hair follicles and sweat glands, with a buildup of collagen around the named structures. From these results, it cannot be concluded if the lesion arose or ended in this specific group. Therefore, Group 3 was renamed “connective tissue rings”. It was observed that lesions were always placed between 2 to 22cm from tail tip, with an average placement of 8 and 7 cm from the tip of the tail of the chronic lesions and the connective tissue rings from the abattoir data, respectively. The average location in the herd data where 7 and 6,25 cm from the tip of the tail, respectively. The lesions circumcised the tail to a varying degree, but in most cases circumcised half of the tail’s circumference. Besides the characteristic placement and distribution, it was found, that the lesions always initially arose on the dorsal surface of the tail. Selected variables were studied, in both datasets, where a univariable and multivariable analyses were

Dette specialeprojekt havde til formål at vurdere, hvordan tid siden sidste vaccination (TSLV), alder og vægt påvirker antistofniveauerne af canine parvovirus (CPV-2), distemper virus (CDV) og adenovirus (CAV) ved at bruge den serologiske patientnære (in-house) antistoftiter-test, VacciCheck®, til at måle antistofniveauer i en population af danske hunde. Studiet inkluderede prøver fra 166 hunde med en kendt sidste vaccinationsdato. Hundene skulle enten være ≳ seks måneder gamle og vaccineret mindst én gang med en modificeret levende kombinationsvaccine mod CDV, CAV og CPV-2 (DHP) inden for seks-måneders-alderen, men ikke revaccineret siden, eller voksne hunde sidst vaccineret ≳ tre år tidligere. De blev kategoriseret i definerede grupper baseret på TSLV, alder og vægt. Prøverne blev analyseret for beskyttende antistoftitre (PATs) defineret som ≥ 1:80 for CPV-2, ≥ 1:32 for CDV og ≥ 1:16 for CAV. Andelen af hunde med PATs var 98,8% for CPV-2, 76,5% for CDV og 88,0% for CAV. Med hensyn til TSLV, var der en generel forskel i CPV-2’s og CAV’s antistofniveauer mellem grupperne samt en svag negativ korrelation mellem TSLV og CPV-2. Alder viste en generel forskel i CPV-2 antistofniveauer mellem grupperne og en moderat negativ korrelation mellem alder og CPV-2 samt en svag negativ korrelation for CAV. Derudover havde vægt og CPV-2 også en svag negativ korrelation. På trods af resultaterne, som indikerer en sammenhæng mellem en stigning i disse tre faktorer og et fald i CPV-2 antistofniveauer samt en tendens til at CAV antistofniveauet falder med stigende TSLV og alder, konkluderes det stadig, at udviklingen og opretholdelsen af antistofniveau efter vaccination er meget individuel og afhænger af forskellige andre faktorer, som påvirker denne proces. Selvom flertallet af de inkluderede hunde opretholder PATs i mere end tre år, manglede 15 (11.2%) ud af 134 hunde over ét år PATs for én eller to sygdomme og havde en TSLV på ≤ tre år. Af de 32 juvenile hunde manglede 9 (28.1%) PA, This master’s thesis aimed to assess the influence of time since last vaccination (TSLV), age, and weight on antibody titre levels, by utilising the serological in-house antibody titre test, VacciCheck®, to measure antibody titres against canine parvovirus (CPV-2), distemper virus (CDV), and adenovirus (CAV) in a population of Danish dogs. The study included samples from 166 dogs with a known last date of vaccination. They were required to be either aged ≳ six months and vaccinated at least once with a modified live combination vaccine against CDV, CAV, and CPV-2 (DHP) before six months of age but not revaccinated since, or adult dogs last vaccinated ≳ three years prior to presentation. The dogs were categorised into defined groups based on TSLV, age, and weight. Samples were analysed for protective antibody titres (PAT) defined as ≥ 1:80 for CPV-2, ≥ 1:32 for CDV, and ≥ 1:16 for CAV. The percentage of dogs with PATs was 98.8% for CPV-2, 76.5% for CDV, and 88.0% for CAV. In terms of TSLV, an overall difference for CPV-2 and CAV antibody titres was observed between the groups as well as a weak negative correlation between TSLV and CPV-2. Age demonstrated an overall difference in CPV-2 antibody titres among groups and a moderate negative correlation between age and CPV-2 as well as a weak negative correlation for CAV. Additionally, weight and CPV-2 also had a weak negative correlation. Despite the results indicating that as these three factors increase, the CPV-2 antibody titres decrease, and that there is a tendency for CAV antibody titres to decrease with increasing TSLV and age, it is still concluded that the development and the longevity of antibodies following vaccination are highly individualised for each dog and dependent on various other factors that influence this process. Though the majority of the included dogs maintained a PAT for more than three years, 15 (11.2%) out of 134 dogs over one year of age lacked PATs for one or two diseases and had a TSLV ≤ thr

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) and major depressive disorder (MDD) are two highly prevalent disorders that frequently co-occur. Prior evidence from genetic and cohort studies supports an association between ADHD and MDD. However, the direction and mechanisms underlying their association remain unclear. As ADHD onsets in early life, it has been hypothesized that ADHD may cause MDD. METHODS: In this study, we examined the association of ADHD with MDD using three different genetically informed methods to disentangle causality from confounding: 1) a nationwide longitudinal register-based full sibling comparison (N=1,018,489) adjusting for shared familial confounding; 2) a prospective co-twin control study comprising 16,447 twins (5,084 monozygotic and 11,393 dizygotic); and 3) a two-sample Mendelian randomization analysis using the largest available ADHD (N=225,534) and MDD (N=500,199) genome wide association (GWAS) summary statistics, adjusting for correlated and uncorrelated horizontal pleiotropy. RESULTS: Sibling and twin comparisons indicated that individuals with ADHD have an increased risk for subsequent development of MDD (HR=4.12 [3.62-4.69]) after adjusting for shared genetic and familial factors, and that ADHD scores endorsed by parents are positively associated with subsequent MDD scores at ages 15 and 18 years (b=0.07 [0.05-0.08]) and b=0.09 [0.08-0.11], respectively). Mendelian randomization analyses showed that genetic liability for ADHD is causally related to MDD (OR=1.15 [1.08-1.23]). CONCLUSIONS: Our study provided consistent results across three different genetically informative approaches, strengthening the hypothesis that ADHD is causally related to MDD., This work was supported by the European Union's Horizon 2020 research and innovation programme (Grant No. 965381) , Swedish Research Council (Grant No. 2018-02599 [to HL] ) , Hjarnfonden (Swedish Brain Foundation) (Grant No. FO2021-0115 [to HL] , and to IB) , Fredrik och Ingrid Thurings Stiftelse (Grant No. 2020-00610 [to IB] ) , Wolfson Centre for Young People's Mental Health (to AT) , Novo Nordisk Foundation (Grant No. NNF20OC0065561 [to DD] ) , and Lundbeck Foundation (Grant No. R344-2020-1060 [to DD] ).

The risk for a severe coronavirus disease 2019 (COVID-19) with need for an intensive care unit (ICU) admission in a non-immunocompromised vaccinated population dropped from 5% at the beginning of the pandemic to at least 0.2% and is still decreasing since the omicron strain dominates the COVID-19 pandemic [1]. Beyond the risk factors identified for a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection like male sex, older age, and comorbidities such as cardiovascular disease, lung disease or obesity, patients with a history of malignancy, specifically patients with haematological malignancy, are prone to develop a complicated SARS-CoV-2 infection with need for ICU which is still associated with poorer clinical outcome [2,3,4,5,6,7,8,9,10,11,12,13,14,15]. The circumstances of a widely heterogenous population with regards to the type of haematological malignancy, extent of disease, haematological malignancy treatment history, [16,17,18] and baseline performance status are even more challenging in the environment of an ICU [19]. Although, data referring to critically ill COVID-19 patients regarding treatment strategies and outcome are widely available, data referring to critically ill patients with haematological malignancy are scarce and underreported [20]. The aim of this study is to analyze the epidemiology, risk factors and outcome of patients with haematological malignancy with need for an ICU setting using the data from the large-scale EPICOVIDEHA registry of the European Hematology Association—Scientific Working Group Infectious in Hematology (EHA-SWG) [21].

The COVID-19 pandemic heightened risks for individuals with hematological malignancies due to compromised immune systems, leading to more severe outcomes and increased mortality. While interventions like vaccines, targeted antivirals, and monoclonal antibodies have been effective for the general population, their benefits for these patients may not be as pronounced.

Since the beginning of the COVID-19 pandemic, there has been an overall improvement in patient mortality. However, haematological malignancy patients continue to experience significant impacts from COVID-19, including high rates of hospitalization, intensive care unit (ICU) admissions, and mortality. In comparison to other haematological malignancy patients, individuals with chronic myeloid leukemia (CML) generally have better prognosis. This study, conducted using a large haematological malignancy patient database (EPICOVIDEHA), demonstrated that the majority of CML patients experienced mild infections. The decline in severe and critical infections over the years can largely be attributed to the widespread administration of vaccinations and the positive response they elicited. Notably, the mortality rate among CML patients was low and exhibited a downward trend in subsequent years. Importantly, our analysis provided confirmation of the effectiveness of vaccinations in CML patients.

We have detected solar-like oscillations in the mid K-dwarf $\varepsilon$ Indi A, making it the coolest dwarf to have measured oscillations. The star is noteworthy for harboring a pair of brown dwarf companions and a Jupiter-type planet. We observed $\varepsilon$ Indi A during two radial velocity campaigns, using the high-resolution spectrographs HARPS (2011) and UVES (2021). Weighting the time series, we computed the power spectra and established the detection of solar-like oscillations with a power excess located at $5265 \pm 110 \ \mu$Hz -- the highest frequency solar-like oscillations so far measured in any star. The measurement of the center of the power excess allows us to compute a stellar mass of $0.782 \pm 0.023 \ M_\odot$ based on scaling relations and a known radius from interferometry. We also determine the amplitude of the peak power and note that there is a slight difference between the two observing campaigns, indicating a varying activity level. Overall, this work confirms that low-amplitude solar-like oscillations can be detected in mid-K type stars in radial velocity measurements obtained with high-precision spectrographs., Comment: 10 pages, 3 figures, accepted for publication in ApJ

Introduction: The internet is a popular source of health information including images of disease manifestations. Online photographs of skin lesions may aid patients in identifying their disease, if these pictures are of good quality and of the disease they claim to show. If not, patients may be at risk of delayed diagnosis, misdiagnosis, and suboptimal treatment. For urticaria, the mismatch rate and quality of online pictures are unknown. The objective of this study was therefore to evaluate the content and quality of online images of urticaria. Methods: The search term "urticaria"was applied to Google Images and Shutterstock. The top 100 photographs from each search engine were retrieved on October 9th, 2022. Illustrations, drawings, and heavily edited photographs were excluded. Each image was evaluated for patient characteristics, characteristics of urticarial lesions, and image quality. Results: Across 194 unique images of urticaria (after removing duplicates), 35 (18.0%) did not depict urticarial lesions, and 38 (19.6%) were ambiguous. Less than two-thirds of images 121 (62.4%) showed bona fide urticarial lesions. Pictures of urticarial lesions under-represented children and did not reflect female preponderance of the disease. Images predominantly depicted urticaria lesions on Caucasian skin (59.8%) and were typical of spontaneous rather than inducible urticaria. Only 3 (1.5%) pictures showed angioedema, a common clinical sign in patients with urticaria. The overall quality of online urticaria pictures was mostly good or very good. Conclusion: Physicians and patients should be aware that one in five online pictures of urticaria does not show urticarial skin lesions, and children, females, non-Caucasian patients, inducible urticaria, and angioedema are under-represented. These findings should prompt efforts to improve the accuracy and representativeness of online urticaria pictures.

The fetal development of organs and functions is vulnerable to perturbation by maternal inflammation which may increase susceptibility to disorders after birth. Because it is not well understood how the placenta and fetus respond to acute lung- inflammation, we characterize the response to maternal pulmonary lipopolysaccharide exposure across 24 h in maternal and fetal organs using multi-omics, imaging and integrative analyses. Unlike maternal organs, which mount strong inflammatory immune responses, the placenta upregulates immuno-modulatory genes, in particular the IL-6 signaling suppressor Socs3. Similarly, we observe no immune response in the fetal liver, which instead displays metabolic changes, including increases in lipids containing docosahexaenoic acid, crucial for fetal brain development. The maternal liver and plasma display similar metabolic alterations, potentially increasing bioavailability of docosahexaenoic acid for the mother and fetus. Thus, our integrated temporal analysis shows that systemic inflammation in the mother leads to a metabolic perturbation in the fetus., The fetal development of organs and functions is vulnerable to perturbation by maternal inflammation which may increase susceptibility to disorders after birth. Because it is not well understood how the placenta and fetus respond to acute lung- inflammation, we characterize the response to maternal pulmonary lipopolysaccharide exposure across 24 h in maternal and fetal organs using multi-omics, imaging and integrative analyses. Unlike maternal organs, which mount strong inflammatory immune responses, the placenta upregulates immuno-modulatory genes, in particular the IL-6 signaling suppressor Socs3. Similarly, we observe no immune response in the fetal liver, which instead displays metabolic changes, including increases in lipids containing docosahexaenoic acid, crucial for fetal brain development. The maternal liver and plasma display similar metabolic alterations, potentially increasing bioavailability of docosahexaenoic acid for the mother and fetus. Thus, our integrated temporal analysis shows that systemic inflammation in the mother leads to a metabolic perturbation in the fetus.

Hypothalamic-pituitary-adrenal (HPA)-axis hyperactivity measured by the combined dexamethasone-CRH test (DEX-CRH test) has been found in patients with major depressive disorder (MDD), whereas hypoactivity has been found in patients with work-related stress. We aimed to investigate the DEX-CRH test as a biomarker to distinguish between MDD and work-related stress (exhaustion disorder - ED). We hypothesized that there would be lower cortisol and ACTH response in participants with ED compared to MDD and healthy controls (HC). Also, we explored if the cortisol response of those patients interacted with robust markers of oxidative stress. Thirty inpatients with MDD and 23 outpatients with ED were recruited. Plasma cortisol and ACTH were sampled during a DEX-CRH test. The main outcome measure, area under the curve (AUC) for cortisol and ACTH, was compa-red between MDD vs. ED participants and a historical HC group. Secondary markers of oxidative stress urinary 8-oxodG and 8-oxoGuo; quality of sleep and psychometrics were obtained. Cortisol concentrations were higher in MDD and ED participants compared to HC, and no differences in AUC cortisol and ACTH were found between ED vs. MDD. Compared to ED, MDD participants had higher stress symptom severity and a lower sense of well-being. No differences in oxidative stress markers or quality of sleep between the groups were found. The result indicates that the patients with ED, like patients with MDD, are non-suppressors in DEX-CRH test and not hypocortisolemic as suggested., Hypothalamic-pituitary-adrenal (HPA)-axis hyperactivity measured by the combined dexamethasone-CRH test (DEX-CRH test) has been found in patients with major depressive disorder (MDD), whereas hypoactivity has been found in patients with work-related stress. We aimed to investigate the DEX-CRH test as a biomarker to distinguish between MDD and work-related stress (exhaustion disorder - ED). We hypothesized that there would be lower cortisol and ACTH response in participants with ED compared to MDD and healthy controls (HC). Also, we explored if the cortisol response of those patients interacted with robust markers of oxidative stress. Thirty inpatients with MDD and 23 outpatients with ED were recruited. Plasma cortisol and ACTH were sampled during a DEX-CRH test. The main outcome measure, area under the curve (AUC) for cortisol and ACTH, was compa-red between MDD vs. ED participants and a historical HC group. Secondary markers of oxidative stress urinary 8-oxodG and 8-oxoGuo; quality of sleep and psychometrics were obtained. Cortisol concentrations were higher in MDD and ED participants compared to HC, and no differences in AUC cortisol and ACTH were found between ED vs. MDD. Compared to ED, MDD participants had higher stress symptom severity and a lower sense of well-being. No differences in oxidative stress markers or quality of sleep between the groups were found. The result indicates that the patients with ED, like patients with MDD, are non-suppressors in DEX-CRH test and not hypocortisolemic as suggested.

Brief introduction: What are microclimates and why are they important?: Microclimate science has developed into a global discipline. Microclimate science is increasingly used to understand and mitigate climate and biodiversity shifts. Here, we provide an overview of the current status of microclimate ecology and biogeography in terrestrial ecosystems, and where this field is heading next. Microclimate investigations in ecology and biogeography: We highlight the latest research on interactions between microclimates and organisms, including how microclimates influence individuals, and through them populations, communities and entire ecosystems and their processes. We also briefly discuss recent research on how organisms shape microclimates from the tropics to the poles. Microclimate applications in ecosystem management: Microclimates are also important in ecosystem management under climate change. We showcase new research in microclimate management with examples from biodiversity conservation, forestry and urban ecology. We discuss the importance of microrefugia in conservation and how to promote microclimate heterogeneity. Methods for microclimate science: We showcase the recent advances in data acquisition, such as novel field sensors and remote sensing methods. We discuss microclimate modelling, mapping and data processing, including accessibility of modelling tools, advantages of mechanistic and statistical modelling and solutions for computational challenges that have pushed the state-of-the-art of the field. What's next?: We identify major knowledge gaps that need to be filled for further advancing microclimate investigations, applications and methods. These gaps include spatiotemporal scaling of microclimate data, mismatches between macroclimate and microclimate in predicting responses of organisms to climate change, and the need for more evidence on the outcomes of microclimate management.

The aim of the study was to characterise and determine the prevalence of band-shaped tail lesions in Holstein cows. Lesions were present either as wounds or by epithelised granulation/connective tissue formations. Both types were characterised by a median localisation 7 cm from the tip of the tail, and they occurred on the dorsal aspect of the tail. From here they encircled the tail either completely or in varying degrees, and they were often present as isolated lesions (93%). The prevalence of band-shaped tail lesions was found to be 25% among 2099 cows examined in 16 Danish Holstein herds with a variation from 18 to 40% between herds. In the herds, the wound lesions and the connective tissue formations accounted for 22% and 78% of all band-shaped tail lesions, respectively. Among 458 Holstein cows examined at an abattoir the prevalence of band-shaped tail lesions was 23%, i.e. similar to the prevalence within the herds. At the abattoir the share of band-shaped wound lesions was 67% and the band-shaped connective tissue formation 33%. Associations between the occurrence of band-shaped tail lesions and parity and lack of the tail tip were observed.

STUDY QUESTION Do children born after ART have a higher risk of developing Type 1 diabetes (DM1) than children conceived without ART? SUMMARY ANSWER The risk of DM1 was similar for children conceived with and without ART, and there were no clear differences in risk according to method of fertility treatment. WHAT IS KNOWN ALREADY ART is associated with a higher risk of adverse perinatal outcomes, and the risk depends on the method of ART. The Developmental Origins of Health and Disease theory proposes that prenatal stress can provoke changes in endocrine processes which impact health later in life. STUDY DESIGN, SIZE, DURATION A Nordic register-based cohort study was carried out, including all children born in Denmark (birth years 1994–2014), Finland (1990–2014), and Norway (1984–2015). The study included 76 184 liveborn singletons born after ART and 4 403 419 born without ART. Median follow-up was 8.3 and 13.7 years in the ART and non-ART group, respectively. PARTICIPANTS/MATERIALS, SETTING, METHODS The cohort, initiated by the Committee of Nordic Assisted Reproductive Technology and Safety (CoNARTaS), was established by linking national registry data from the medical birth registries and national patient registries available in the Nordic countries. We performed multivariable logistic regression analyses for the birth year intervals 1984–1990, 1991–1995, 1996–2000, 2001–2005, 2006–2010, and 2011–2015, while adjusting for year of birth within each interval, sex of the child, parity, maternal age, maternal diabetes, and maternal smoking during pregnancy as potential confounders. MAIN RESULTS AND THE ROLE OF CHANCE During follow-up, 259 (3.4‰) children born after ART were diagnosed with DM1, while this was the case for 22 209 (5.0‰) born without ART, corresponding to an adjusted odds ratio of 0.98 (95% CI: 0.861.11). Within the different birth year intervals, no significant difference in risk of DM1, STUDY QUESTION: Do children born after ART have a higher risk of developing Type 1 diabetes (DM1) than children conceived without ART?SUMMARY ANSWER: The risk of DM1 was similar for children conceived with and without ART, and there were no clear differences in risk according to method of fertility treatment.WHAT IS KNOWN ALREADY: ART is associated with a higher risk of adverse perinatal outcomes, and the risk depends on the method of ART. The Developmental Origins of Health and Disease theory proposes that prenatal stress can provoke changes in endocrine processes which impact health later in life.STUDY DESIGN SIZE DURATION: A Nordic register-based cohort study was carried out, including all children born in Denmark (birth years 1994-2014), Finland (1990-2014), and Norway (1984-2015). The study included 76 184 liveborn singletons born after ART and 4 403 419 born without ART. Median follow-up was 8.3 and 13.7 years in the ART and non-ART group, respectively.PARTICIPANTS/MATERIALS SETTING METHODS: The cohort, initiated by the Committee of Nordic Assisted Reproductive Technology and Safety (CoNARTaS), was established by linking national registry data from the medical birth registries and national patient registries available in the Nordic countries. We performed multivariable logistic regression analyses for the birth year intervals 1984-1990, 1991-1995, 1996-2000, 2001-2005, 2006-2010, and 2011-2015, while adjusting for year of birth within each interval, sex of the child, parity, maternal age, maternal diabetes, and maternal smoking during pregnancy as potential confounders.MAIN RESULTS AND THE ROLE OF CHANCE: During follow-up, 259 (3.4‰) children born after ART were diagnosed with DM1, while this was the case for 22 209 (5.0‰) born without ART, corresponding to an adjusted odds ratio of 0.98 (95% CI: 0.861.11). Within the different birth year intervals, no significant difference in risk of DM1 between the two groups was found

Aims/hypothesis Diabetic gastroenteropathy frequently causes debilitating gastrointestinal symptoms. Previous uncontrolled studies have shown that transcutaneous vagal nerve stimulation (tVNS) may improve gastrointestinal symptoms. To investigate the effect of cervical tVNS in individuals with diabetes suffering from autonomic neuropathy and gastrointestinal symptoms, we conducted a randomised, sham-controlled, double-blind (participants and investigators were blinded to the allocated treatment) study. Methods This study included adults (aged 20–86) with type 1 or 2 diabetes, gastrointestinal symptoms and autonomic neuropathy recruited from three Steno Diabetes Centres in Denmark. Participants were randomly allocated 1:1 to receive active or sham stimulation. Active cervical tVNS or sham stimulation was self-administered over two successive study periods: 1 week of four daily stimulations and 8 weeks of two daily stimulations. The primary outcome measures were gastrointestinal symptom changes as measured using the gastroparesis cardinal symptom index (GCSI) and the gastrointestinal symptom rating scale (GSRS). Secondary outcomes included gastrointestinal transit times and cardiovascular autonomic function. Results Sixty-eight participants were randomised to the active group, while 77 were randomised to the sham group. Sixty-three in the active and 68 in the sham group remained for analysis in study period 1, while 62 in each group were analysed in study period 2. In study period 1, active and sham tVNS resulted in similar symptom reductions (GCSI: −0.26 ± 0.64 vs −0.17 ± 0.62, p=0.44; GSRS: −0.35 ± 0.62 vs −0.32 ± 0.59, p=0.77; mean ± SD). In study period 2, active stimulation also caused a mean symptom decrease that was comparable to that observed after sham stimulation (GCSI: −0.47 ± 0.78 vs −0.33 ± 0.75, p=0.34; GSRS: −0.46 ± 0.90 vs −0.35 ± 0.79, p=0.50). Gastric emptying time was increased in the active group compared with sham (23, Aims/hypothesis: Diabetic gastroenteropathy frequently causes debilitating gastrointestinal symptoms. Previous uncontrolled studies have shown that transcutaneous vagal nerve stimulation (tVNS) may improve gastrointestinal symptoms. To investigate the effect of cervical tVNS in individuals with diabetes suffering from autonomic neuropathy and gastrointestinal symptoms, we conducted a randomised, sham-controlled, double-blind (participants and investigators were blinded to the allocated treatment) study. Methods: This study included adults (aged 20–86) with type 1 or 2 diabetes, gastrointestinal symptoms and autonomic neuropathy recruited from three Steno Diabetes Centres in Denmark. Participants were randomly allocated 1:1 to receive active or sham stimulation. Active cervical tVNS or sham stimulation was self-administered over two successive study periods: 1 week of four daily stimulations and 8 weeks of two daily stimulations. The primary outcome measures were gastrointestinal symptom changes as measured using the gastroparesis cardinal symptom index (GCSI) and the gastrointestinal symptom rating scale (GSRS). Secondary outcomes included gastrointestinal transit times and cardiovascular autonomic function. Results: Sixty-eight participants were randomised to the active group, while 77 were randomised to the sham group. Sixty-three in the active and 68 in the sham group remained for analysis in study period 1, while 62 in each group were analysed in study period 2. In study period 1, active and sham tVNS resulted in similar symptom reductions (GCSI: −0.26 ± 0.64 vs −0.17 ± 0.62, p=0.44; GSRS: −0.35 ± 0.62 vs −0.32 ± 0.59, p=0.77; mean ± SD). In study period 2, active stimulation also caused a mean symptom decrease that was comparable to that observed after sham stimulation (GCSI: −0.47 ± 0.78 vs −0.33 ± 0.75, p=0.34; GSRS: −0.46 ± 0.90 vs −0.35 ± 0.79, p=0.50). Gastric emptying time was increased in the active group compared with sham (23 min vs −19 min, p=0.04)

INTRODUCTION: Psoriasis is a chronic T-cell-mediated inflammatory and proliferative skin disease. Chronic obstructive pulmonary disease (COPD) is an inflammatory disease of the airways. COPD has been studied as a comorbidity of psoriasis, but the association needs further study, hence the objective of this study. eVIDeNCe aCQuISItIoN: a systematic review was performed using the database Pubmed and 155 records were found including the ones found through references. Seven records were found eligible for this study including six observational studies and one experimental study with a total of 229,075 participants. the odds ratio of CoPD in patients with psoriasis and healthy subjects was analysed using a random effects model. EVIDENCE SYNTHESIS: The pooled data showed a significant association (OR=1.77, 95% CI [1.32; 2.39]) between psoriasis and COPD with high inter-study heterogeneity (I2=96%). Sub-analyses of the different types of studies (cohort study: OR=2.53 [2.43; 2.63], case-control study: OR=1.6 [0.03; 100.96] and cross-sectional study: OR=1.57 [0.58; 4.22]) and smoking status (OR=1.7 [0.69; 4.14]) were also performed to further examine the association. CONCLUSIONS: There is a significant association between psoriasis and COPD, but the underlying mechanism and how smoking status affects the results remain unclear and need further study. Physicians should be aware of the risk and its seriousness to provide better and more targeted treatment.

Introduction Atrial fibrillation is highly prevalent in patients on chronic dialysis. It is unclear whether anticoagulant therapy for stroke prevention is beneficial in these patients. Vitamin K-antagonists (VKA) remain the predominant anticoagulant choice. Importantly, anticoagulation remains inconsistently used and a possible benefit remains untested in randomised clinical trials comparing oral anticoagulation with no treatment in patients on chronic dialysis. The Danish Warfarin-Dialysis (DANWARD) trial aims to investigate the safety and efficacy of VKAs in patients with atrial fibrillation on chronic dialysis. The hypothesis is that VKA treatment compared with no treatment is associated with stroke risk reduction and overall benefit. Methods and analysis The DANWARD trial is an investigator-initiated trial at 13 Danish dialysis centres. In an open-label randomised clinical trial study design, a total of 718 patients with atrial fibrillation on chronic dialysis will be randomised in a 1:1 ratio to receive either standard dose VKA targeting an international normalised ratio of 2.0–3.0 or no oral anticoagulation. Principal analyses will compare the risk of a primary efficacy endpoint, stroke or transient ischaemic attack and a primary safety endpoint, major bleeding, in patients allocated to VKA treatment and no treatment, respectively. The first patient was randomised in October 2019. Patients will be followed until 1 year after the inclusion of the last patient. Ethics and dissemination The study protocol was approved by the Regional Research Ethics Committee (journal number H-18050839) and the Danish Medicines Agency (case number 2018101877). The trial is conducted in accordance with the Helsinki declaration and standards of Good Clinical Practice. Study results will be disseminated to participating sites, at research conferences and in peer-reviewed journals., Introduction Atrial fibrillation is highly prevalent in patients on chronic dialysis. It is unclear whether anticoagulant therapy for stroke prevention is beneficial in these patients. Vitamin K-antagonists (VKA) remain the predominant anticoagulant choice. Importantly, anticoagulation remains inconsistently used and a possible benefit remains untested in randomised clinical trials comparing oral anticoagulation with no treatment in patients on chronic dialysis. The Danish Warfarin-Dialysis (DANWARD) trial aims to investigate the safety and efficacy of VKAs in patients with atrial fibrillation on chronic dialysis. The hypothesis is that VKA treatment compared with no treatment is associated with stroke risk reduction and overall benefit. Methods and analysis The DANWARD trial is an investigator-initiated trial at 13 Danish dialysis centres. In an open-label randomised clinical trial study design, a total of 718 patients with atrial fibrillation on chronic dialysis will be randomised in a 1:1 ratio to receive either standard dose VKA targeting an international normalised ratio of 2.0-3.0 or no oral anticoagulation. Principal analyses will compare the risk of a primary efficacy endpoint, stroke or transient ischaemic attack and a primary safety endpoint, major bleeding, in patients allocated to VKA treatment and no treatment, respectively. The first patient was randomised in October 2019. Patients will be followed until 1 year after the inclusion of the last patient. Ethics and dissemination The study protocol was approved by the Regional Research Ethics Committee (journal number H-18050839) and the Danish Medicines Agency (case number 2018101877). The trial is conducted in accordance with the Helsinki declaration and standards of Good Clinical Practice. Study results will be disseminated to participating sites, at research conferences and in peer-reviewed journals. Trial registration numbers NCT03862859, EUDRA-CT 2018-000484-86 and CTIS ID 2022-502500-75-00.

Background Most adult smokers started smoking in their teenage years, which increases the risk of nicotine dependence. In Denmark, there is a high prevalence of youth smoking among students in Vocational Education and Training (VET). However, reducing and preventing smoking in this group is a major challenge. This article presents a needs assessment aimed to explore factors sustaining legitimacy of smoking in VET schools and consider the measures needed to prepare VET schools’ implementation of smoking reduction and prevention interventions. Methods Participant observations were conducted in four VET classes representing three VET schools in Denmark with a duration of four days each. Individual, semi-structured interviews were conducted with teachers, managers, and a student advisor, as well as four focus groups with a total of 20 students. Interviews were audio-taped, transcribed, and the data material was analyzed following Malterud’s systematic text condensation. Findings Factors that helped sustain legitimacy of smoking in VET schools included a positive and normalized attitude towards smoking at home and among friends, an understanding of smoking as an integral and expected practice in VET professions and schools, a perceived reliance on smoking as an icebreaker in new social relations and as a pedagogical tool, and smoking as a habit and a means to deal with boredom and stress relief. Conclusions The factors sustaining legitimacy of smoking in VET schools are reciprocal and call for smoking reduction and prevention intervention efforts which consider and address social influence, habitual behavior, and psychological needs, as well as changes at the policy level., BACKGROUND: Most adult smokers started smoking in their teenage years, which increases the risk of nicotine dependence. In Denmark, there is a high prevalence of youth smoking among students in Vocational Education and Training (VET). However, reducing and preventing smoking in this group is a major challenge. This article presents a needs assessment aimed to explore factors sustaining legitimacy of smoking in VET schools and consider the measures needed to prepare VET schools' implementation of smoking reduction and prevention interventions.METHODS: Participant observations were conducted in four VET classes representing three VET schools in Denmark with a duration of four days each. Individual, semi-structured interviews were conducted with teachers, managers, and a student advisor, as well as four focus groups with a total of 20 students. Interviews were audio-taped, transcribed, and the data material was analyzed following Malterud's systematic text condensation.FINDINGS: Factors that helped sustain legitimacy of smoking in VET schools included a positive and normalized attitude towards smoking at home and among friends, an understanding of smoking as an integral and expected practice in VET professions and schools, a perceived reliance on smoking as an icebreaker in new social relations and as a pedagogical tool, and smoking as a habit and a means to deal with boredom and stress relief.CONCLUSIONS: The factors sustaining legitimacy of smoking in VET schools are reciprocal and call for smoking reduction and prevention intervention efforts which consider and address social influence, habitual behavior, and psychological needs, as well as changes at the policy level.

Introduction It is an ongoing debate how much lung and heart irradiation impact overall survival (OS) after definitive radiotherapy for lung cancer. This study uses a large national cohort of patients with locally advanced NSCLC to investigate the association between OS and irradiation of lung and heart. Methods Treatment plans were acquired from six Danish radiotherapy centers, and patient characteristics were obtained from national registries. A hybrid segmentation tool automatically delineated the heart and substructures. Dose-volume histograms for all structures were extracted and analyzed using principal component analyses (PCAs). Parameter selection for a multivariable Cox model for OS prediction was performed using cross-validation based on bootstrapping. Results The population consisted of 644 patients with a median survival of 26 months (95% confidence interval [CI]: 24–29). The cross-validation selected two PCA variables to be included in the multivariable model. PCA1 represented irradiation of the heart and affected OS negatively (hazard ratio, 1.14; 95% CI: 1.04–1.26). PCA2 characterized the left-right balance (right atrium and left ventricle) irradiation, showing better survival for tumors near the right side (hazard ratio, 0.92; 95% CI: 0.84–1.00). Besides the two PCA variables, the multivariable model included age, sex, body-mass index, performance status, tumor dose, and tumor volume. Conclusions Besides the classic noncardiac risk factors, lung and heart doses had a negative impact on survival, while it is suggested that the left side of the heart is a more radiation dose–sensitive region. The data indicate that overall heart irradiation should be reduced to improve the OS if possible., Introduction: It is an ongoing debate how much lung and heart irradiation impact overall survival (OS) after definitive radiotherapy for lung cancer. This study uses a large national cohort of patients with locally advanced NSCLC to investigate the association between OS and irradiation of lung and heart. Methods: Treatment plans were acquired from six Danish radiotherapy centers, and patient characteristics were obtained from national registries. A hybrid segmentation tool automatically delineated the heart and substructures. Dose-volume histograms for all structures were extracted and analyzed using principal component analyses (PCAs). Parameter selection for a multivariable Cox model for OS prediction was performed using cross-validation based on bootstrapping. Results: The population consisted of 644 patients with a median survival of 26 months (95% confidence interval [CI]: 24–29). The cross-validation selected two PCA variables to be included in the multivariable model. PCA1 represented irradiation of the heart and affected OS negatively (hazard ratio, 1.14; 95% CI: 1.04–1.26). PCA2 characterized the left-right balance (right atrium and left ventricle) irradiation, showing better survival for tumors near the right side (hazard ratio, 0.92; 95% CI: 0.84–1.00). Besides the two PCA variables, the multivariable model included age, sex, body-mass index, performance status, tumor dose, and tumor volume. Conclusions: Besides the classic noncardiac risk factors, lung and heart doses had a negative impact on survival, while it is suggested that the left side of the heart is a more radiation dose–sensitive region. The data indicate that overall heart irradiation should be reduced to improve the OS if possible.

INTRODUCTION. Pre-graduate research is popular among medical students. Concerns about time constraints and lack of mentorship have been raised in international studies. The extent to which these issues affect Danish medical students remains unclear. We therefore aimed to assess the conditions and outcomes of pre-graduate research among medical students from the University of Copenhagen. METHODS. A descriptive, cross-sectional, questionnaire-based survey on experiences from pre-graduate research was distributed to medical students and recently graduated medical doctors from the University of Copenhagen who had engaged in full-time pre-graduate research. The survey covered 1) working hours and income, 2) publications and authorship and 3) work environment and well-being. RESULTS. A total of 437 pre-graduate researchers participated in the survey. Pre-graduate research often involved a period outside of medical school (88%) and typically lasted a year (56%), with clinical research being the most common focus (68%). Almost a third worked longer hours (29%) than agreed and additional hours were commonly provided after the research period. Scholarships of 10,000 DKK a month were the primary source of income (72%). Most participants achieved their publication goals (62%) and experiences on work environment and well-being were generally positive. CONCLUSION. Pre-graduate research provides a conducive environment for medical students to engage in scientific research. Hovewer, engaging in pre-graduate research entails long working hours, is inadequately remunerated and often requires students to take leave from medical school. FUNDING. None. TRIAL REGISTRATION. Not relevant.

The objectives were 1) to characterize a Göttingen Minipig model of metabolic syndrome regarding its colon microbiota and circulating microbial products, and 2) to assess whether ovariectomized female and castrated male minipigs show similar phenotypes. Twenty-four nine-week-old Göttingen Minipigs were allocated to four groups based on sex and diet: ovariectomized females and castrated males fed either chow or high-fat diet (HFD) for 12 weeks. At study end, body composition and plasma biomarkers were measured, and a mixed meal tolerance test (MMT) and an intravenous glucose tolerance test (IVGTT) were performed. The HFD groups had significantly higher weight gain, fat percentage, fasting plasma insulin and glucagon compared to the chow groups. Homeostatic model assessment of insulin resistance index (HOMA-IR) was increased and glucose effectiveness derived from the IVGTT and Matsuda´s insulin sensitivity index from the MMT were decreased in the HFD groups. The HFD groups displayed dyslipidemia, with significantly increased total-, LDL- and HDL-cholesterol, and decreased HDL/non-HDL cholesterol ratio. The colon microbiota of HFD minipigs clearly differed from the lean controls (GuniFrac distance matrix). The main bacteria families driving this separation were Clostridiaceae, Fibrobacteraceae, Flavobacteriaceae and Porphyromonadaceae. Moreover, the species richness was significantly decreased by HFD. In addition, HFD decreased the circulating level of short chain fatty acids and beneficial microbial metabolites hippuric acid, xanthine and trigonelline, while increasing the level of branched chain amino acids. Six and nine metabolically relevant genes were differentially expressed between chow-fed and HFD-fed animals in liver and omental adipose tissue, respectively. The HFD-fed pigs presented with metabolic syndrome, gut microbial dysbiosis and a marked decrease in healthy gut microbial products and thus displayed marked parallels to human obesity and insulin resistan, The objectives were 1) to characterize a Göttingen Minipig model of metabolic syndrome regarding its colon microbiota and circulating microbial products, and 2) to assess whether ovariectomized female and castrated male minipigs show similar phenotypes. Twenty-four nine-week-old Göttingen Minipigs were allocated to four groups based on sex and diet: ovariectomized females and castrated males fed either chow or high-fat diet (HFD) for 12 weeks. At study end, body composition and plasma biomarkers were measured, and a mixed meal tolerance test (MMT) and an intravenous glucose tolerance test (IVGTT) were performed. The HFD groups had significantly higher weight gain, fat percentage, fasting plasma insulin and glucagon compared to the chow groups. Homeostatic model assessment of insulin resistance index (HOMA-IR) was increased and glucose effectiveness derived from the IVGTT and Matsuda´s insulin sensitivity index from the MMT were decreased in the HFD groups. The HFD groups displayed dyslipidemia, with significantly increased total-, LDL- and HDL-cholesterol, and decreased HDL/non-HDL cholesterol ratio. The colon microbiota of HFD minipigs clearly differed from the lean controls (GuniFrac distance matrix). The main bacteria families driving this separation were Clostridiaceae, Fibrobacteraceae, Flavobacteriaceae and Porphyromonadaceae. Moreover, the species richness was significantly decreased by HFD. In addition, HFD decreased the circulating level of short chain fatty acids and beneficial microbial metabolites hippuric acid, xanthine and trigonelline, while increasing the level of branched chain amino acids. Six and nine metabolically relevant genes were differentially expressed between chow-fed and HFD-fed animals in liver and omental adipose tissue, respectively. The HFD-fed pigs presented with metabolic syndrome, gut microbial dysbiosis and a marked decrease in healthy gut microbial products and thus displayed marked parallels to human obesity and insulin resis

Modified vaccinia virus Ankara is a versatile vaccine vector, well suited for transgene delivery, with an excellent safety profile. However, certain transgenes render recombinant MVA (rMVA) genetically unstable, leading to the accumulation of mutated rMVA with impaired transgene expression. This represents a major challenge for upscaling and manufacturing of rMVA vaccines. To prevent transgene-mediated negative selection, the continuous avian cell line AGE1.CR pIX (CR pIX) was modified to suppress transgene expression during rMVA generation and amplification. This was achieved by constitutively expressing a tetracycline repressor (TetR) together with a rat-derived shRNA in engineered CR pIX PRO suppressor cells targeting an operator element (tetO) and 3’ untranslated sequence motif on a chimeric poxviral promoter and the transgene mRNA, respectively. This cell line was instrumental in generating two rMVA (isolate CR19) expressing a Macaca fascicularis papillomavirus type 3 (MfPV3) E1E2E6E7 artificially-fused polyprotein following recombination-mediated integration of the coding sequences into the DelIII (CR19 M-DelIII) or TK locus (CR19 M-TK), respectively. Characterization of rMVA on parental CR pIX or engineered CR pIX PRO suppressor cells revealed enhanced replication kinetics, higher virus titers and a focus morphology equaling wild-type MVA, when transgene expression was suppressed. Serially passaging both rMVA ten times on parental CR pIX cells and tracking E1E2E6E7 expression by flow cytometry revealed a rapid loss of transgene product after only few passages. PCR analysis and next-generation sequencing demonstrated that rMVA accumulated mutations within the E1E2E6E7 open reading frame (CR19 M-TK) or deletions of the whole transgene cassette (CR19 M-DelIII). In contrast, CR pIX PRO suppressor cells preserved robust transgene expression for up to 10 passages, however, rMVAs were more stable when E1E2E6E7 was integrated into the TK as compared to the DelIII

INTRODUCTION: Data concerning the global burden of Hidradenitis Suppurativa (HS) are limited. Reported prevalence estimates vary between 0.0003% and 4.1%, and data from various geographical regions are still to be collected. Previously reported prevalence rates have been limited by the methodological approach and source of data. This has resulted in great heterogeneity as prevalence data from physician-diagnosed cases poorly match those of self-reported apparent HS disease.METHODS: The Global Hidradenitis Suppurativa Atlas (GHiSA) introduces an innovative approach to determine the global prevalence of HS. This approach involves using a previously validated questionnaire to screen apparently healthy adults accompanying a patient to a non-dermatological outpatient clinic visit in a hospital. The screening questionnaire (i.e., the index test) is combined with a subsequent physician-based in-person validation (i.e., the reference standard) of the participants who screen positive. Ten percent of the screen-negative participants are also clinically assessed to verify the diagnostic precision of the test. The local prevalence (pi) will be estimated from each country that submits the number of patients who are HS positive according to the index test and clinical examination (n), and the corresponding total number of observations (N).CONCLUSION: The GHiSA Global Prevalence studies are currently running simultaneously in 58 countries across six continents (Africa, Europe, Australia, North America, South America, and Asia). The goal of the combined global proportion is the generation of a single summary (i.e., proportional meta-analysis), which will be done after a logit transformation, and synthesized using a random-effects model. The novel standardization of the Global Prevalence studies conducted through GHiSA enables direct international comparisons, which were previously not possible due to substantial heterogeneity in past HS prevalence studies.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory and scarring disease with a wide spectrum of disease severity. The amount of scaring is proportional to the preceding tissue damage and pose a challenge to patients. Severe HS is most often treatment recalcitrant, but hypothetically avoidable through early biologic treatment. Early prediction of individual risk of disease progression is therefore essential for patient management.OBJECTIVES: To investigate risk factors associated with disease progression and to design an algorithm capable of predicting disease progression.METHODS: A prospective cohort study of 335 patients without severe HS followed for a median of 2 years. Potential risk factors covered basic demographics, HS anamnestic factors and clinical HS factors collected during physical examination. Two separate Cox proportional hazard regression (CPHR) analyses were conducted. A summated "progression score" was calculated and used in the predictive algorithm of severe disease. Subsequent bootstrap sampling was used to validate the predictability of the predictive algorithm.RESULTS: The CPHR analysis of Transition to severe disease found that active smoking (HR = 4.01, 95% CI: 1.71-9.40, p = 0.001); BMI >25 at baseline (each point: HR = 1.06, 95% CI: 1.02-1.09, p < 0.001); active disease in 2 (HR = 4.26, 95% CI: 1.23-14.84, p = 0.02); and ≥3 areas (HR = 6.54, 95% CI: 1.89-22.72, p = 0.003) all constituted substantial risk factors. Conversely the CPHR analysis of Disease progression did not yield results of clinical relevance.A "progression score" of 3.04 was used as a threshold in the predictive algorithm of Transition to severe disease and achieved the following test specifics: sensitivity = 0.51, specificity = 0.86, positive predictive value = 0.50, negative predictive value = 0.86.CONCLUSIONS: We found a disparity between factors increasing the risk of simple Disease progression and those increasing the

The microbiological analysis of wastewater samples is increasingly used for the surveillance of SARS-CoV-2 globally. We described the setup process of the national SARS-CoV-2 wastewater-based surveillance system in Denmark, presented its main results during the first year of activities, from July 2021 to June 2022, and discussed their operational significance. The Danish SARS-CoV-2 wastewater-based surveillance system was designed to cover 85 % of the population in Denmark and it entailed taking three weekly samples from 230 sites. Samples were RT-qPCR tested for SARS-CoV-2 RNA, targeting the genetic markers N1, N2 and RdRp, and for two faecal indicators, Pepper Mild Mottle Virus and crAssphage. We calculated the weekly SARS-CoV-2 RNA concentration in the wastewater from each sampling site and monitored it in view of the results from individual testing, at the national and regional levels. We attempted to use wastewater results to identify potential local outbreaks, and we sequenced positive wastewater samples using Nanopore sequencing to monitor the circulation of viral variants in Denmark. The system reached its full implementation by October 2021 and covered up to 86.4 % of the Danish population. The system allowed for monitoring of the national and regional trends of SARS-CoV-2 infections in Denmark. However, the system contribution to the identification of potential local outbreaks was limited by the extensive information available from clinical testing. The sequencing of wastewater samples identified relevant variants of concern, in line with results from sequencing of human samples. Amidst the COVID-19 pandemic, Denmark implemented a nationwide SARS-CoV-2 wastewater-based surveillance system that integrated routine surveillance from individual testing. Today, while testing for COVID-19 at the community level has been discontinued, the system is on the frontline to monitor the occurrence and spread of SARS-CoV-2 in Denmark., The microbiological analysis of wastewater samples is increasingly used for the surveillance of SARS-CoV-2 globally. We described the setup process of the national SARS-CoV-2 wastewater-based surveillance system in Denmark, presented its main results during the first year of activities, from July 2021 to June 2022, and discussed their operational significance. The Danish SARS-CoV-2 wastewater-based surveillance system was designed to cover 85 % of the population in Denmark and it entailed taking three weekly samples from 230 sites. Samples were RT-qPCR tested for SARS-CoV-2 RNA, targeting the genetic markers N1, N2 and RdRp, and for two faecal indicators, Pepper Mild Mottle Virus and crAssphage. We calculated the weekly SARS-CoV-2 RNA concentration in the wastewater from each sampling site and monitored it in view of the results from individual testing, at the national and regional levels. We attempted to use wastewater results to identify potential local outbreaks, and we sequenced positive wastewater samples using Nanopore sequencing to monitor the circulation of viral variants in Denmark. The system reached its full implementation by October 2021 and covered up to 86.4 % of the Danish population. The system allowed for monitoring of the national and regional trends of SARS-CoV-2 infections in Denmark. However, the system contribution to the identification of potential local outbreaks was limited by the extensive information available from clinical testing. The sequencing of wastewater samples identified relevant variants of concern, in line with results from sequencing of human samples. Amidst the COVID-19 pandemic, Denmark implemented a nationwide SARS-CoV-2 wastewater-based surveillance system that integrated routine surveillance from individual testing. Today, while testing for COVID-19 at the community level has been discontinued, the system is on the frontline to monitor the occurrence and spread of SARS-CoV-2 in Denmark.

Women living with human immunodeficiency virus (HIV) today have life expectancies comparable to the general female population, leading to a growing number transitioning through menopause. Recent studies have highlighted healthcare professionals' lack of confidence in managing menopause in women with HIV, raising concerns about potential mismanagement. This review explores and compares information on menopause management in HIV-specific and general guidelines, with the aim of identifying disparities and assessing the comprehensiveness of HIV guidelines. The focus is on three key areas: the diagnosis of menopause, and the assessment and treatment of menopausal symptoms. Additionally, the review evaluates the usage and characteristics of menopausal symptom assessment scales known to have been used in studies involving women living with HIV. In total, five HIV and six general menopause management guidelines, published between 2015 and 2023, were identified through medical databases, internet search engines and searches of reference lists. Five menopausal symptom assessment scales were also included for review. The findings suggest minimal differences in recommendations for treating menopausal symptoms. The HIV guidelines include recommendations on screening for menopause, and some raise awareness of the possibility of drug-to-drug interactions, but none offers guidance on how to diagnose menopause or how to differentiate between HIV-related and menopause-related symptoms. Upon examining the characteristics of the menopausal symptom assessment scales, we found that none had been validated specifically for women with HIV. In conclusion, this review advocates for the development of a comprehensive guideline that addresses all relevant factors in managing menopause in women with HIV., Women living with human immunodeficiency virus (HIV) today have life expectancies comparable to the general female population, leading to a growing number transitioning through menopause. Recent studies have highlighted healthcare professionals' lack of confidence in managing menopause in women with HIV, raising concerns about potential mismanagement. This review explores and compares information on menopause management in HIV-specific and general guidelines, with the aim of identifying disparities and assessing the comprehensiveness of HIV guidelines. The focus is on three key areas: the diagnosis of menopause, and the assessment and treatment of menopausal symptoms. Additionally, the review evaluates the usage and characteristics of menopausal symptom assessment scales known to have been used in studies involving women living with HIV. In total, five HIV and six general menopause management guidelines, published between 2015 and 2023, were identified through medical databases, internet search engines and searches of reference lists. Five menopausal symptom assessment scales were also included for review. The findings suggest minimal differences in recommendations for treating menopausal symptoms. The HIV guidelines include recommendations on screening for menopause, and some raise awareness of the possibility of drug-to-drug interactions, but none offers guidance on how to diagnose menopause or how to differentiate between HIV-related and menopause-related symptoms. Upon examining the characteristics of the menopausal symptom assessment scales, we found that none had been validated specifically for women with HIV. In conclusion, this review advocates for the development of a comprehensive guideline that addresses all relevant factors in managing menopause in women with HIV.

Lysosomes are acidic organelles responsible for lipid catabolism, and their func-tions can be disrupted by cationic amphiphilic drugs that neutralize lumenal pH and thereby inhibit most lysosomal hydrolases. These drugs can also induce lysosomal membrane per-meabilization and cancer cell death, but the underlying mechanism remains elusive. Here, we uncover that the cationic amphiphilic drugs induce a substantial accumulation of cytolytic lysoglycerophospholipids within the lysosomes of cancer cells, and thereby prevent the recycling of lysoglycerophospholipids to produce common membrane glycerophospholipids. Using quantitative mass spectrometry-based shotgun lipidomics, we demonstrate that struc-turally diverse cationic amphiphilic drugs, along with other types of lysosomal pH-neutraliz-ing reagents, elevate the amounts of lysoglycerophospholipids in MCF7 breast carcinoma cells. Lysoglycerophospholipids constitute ∼11 mol% of total glycerophospholipids in lyso-somes purified from MCF7 cells, compared with ∼1 mol% in the cell lysates. Treatment with cationic amphiphilic drug siramesine further elevates the lysosomal lysoglycerophospholipid content to ∼24 mol% of total glycerophospholipids. Exogenously added traceable lysophos-phatidylcholine is rapidly acylated to form diacylphosphatidylcholine, but siramesine treat-ment sequesters the lysophosphatidylcholine in the lysosomes and prevents it from undergo-ing acylation. These findings shed light on the unexplored role of lysosomes in the recycling of lysoglycerophospholipids and uncover the mechanism of action of promising anticancer agents., Lysosomes are acidic organelles responsible for lipid catabolism, and their functions can be disrupted by cationic amphiphilic drugs that neutralize lumenal pH and thereby inhibit most lysosomal hydrolases. These drugs can also induce lysosomal membrane permeabilization and cancer cell death, but the underlying mechanism remains elusive. Here, we uncover that the cationic amphiphilic drugs induce a substantial accumulation of cytolytic lysoglycerophospholipids within the lysosomes of cancer cells, and thereby prevent the recycling of lysoglycerophospholipids to produce common membrane glycerophospholipids. Using quantitative mass spectrometry-based shotgun lipidomics, we demonstrate that structurally diverse cationic amphiphilic drugs, along with other types of lysosomal pH-neutralizing reagents, elevate the amounts of lysoglycerophospholipids in MCF7 breast carcinoma cells. Lysoglycerophospholipids constitute ∼11 mol% of total glycerophospholipids in lysosomes purified from MCF7 cells, compared with ∼1 mol% in the cell lysates. Treatment with cationic amphiphilic drug siramesine further elevates the lysosomal lysoglycerophospholipid content to ∼24 mol% of total glycerophospholipids. Exogenously added traceable lysophosphatidylcholine is rapidly acylated to form diacylphosphatidylcholine, but siramesine treatment sequesters the lysophosphatidylcholine in the lysosomes and prevents it from undergoing acylation. These findings shed light on the unexplored role of lysosomes in the recycling of lysoglycerophospholipids and uncover the mechanism of action of promising anticancer agents.

Mineral and bone disorders (MBD) are common in patients with chronic kidney disease (CKD), contributing to significant morbidity and mortality. For several decades, the first-line approach to controlling hyperparathyroidism in CKD was by exogenous calcium loading. Since the turn of the millennium, however, a growing awareness of vascular calcification risk has led to a paradigm shift in management and a move away from calcium-based phosphate binders. As a consequence, contemporary CKD patients may be at risk of a negative calcium balance, which, in turn, may compromise bone health, contributing to renal bone disease and increased fracture risk. A calcium intake below a certain threshold may be as problematic as a high intake, worsening the MBD syndrome of CKD, but is not addressed in current clinical practice guidelines. The CKD-MBD and European Renal Nutrition working groups of the European Renal Association (ERA), together with the CKD-MBD and Dialysis working groups of the European Society for Pediatric Nephrology (ESPN), developed key evidence points and clinical practice points on calcium management in children and adults with CKD across stages of disease. These were reviewed by a Delphi panel consisting of ERA and ESPN working groups members. The main clinical practice points include a suggested total calcium intake from diet and medications of 800–1000 mg/day and not exceeding 1500 mg/day to maintain a neutral calcium balance in adults with CKD. In children with CKD, total calcium intake should be kept within the age-appropriate normal range. These statements provide information and may assist in decision-making, but in the absence of high-level evidence must be carefully considered and adapted to individual patient needs., Mineral and bone disorders (MBD) are common in patients with chronic kidney disease (CKD), contributing to significant morbidity and mortality. For several decades, the first-line approach to controlling hyperparathyroidism in CKD was by exogenous calcium loading. Since the turn of the millennium, however, a growing awareness of vascular calcification risk has led to a paradigm shift in management and a move away from calcium-based phosphate binders. As a consequence, contemporary CKD patients may be at risk of a negative calcium balance, which, in turn, may compromise bone health, contributing to renal bone disease and increased fracture risk. A calcium intake below a certain threshold may be as problematic as a high intake, worsening the MBD syndrome of CKD, but is not addressed in current clinical practice guidelines. The CKD-MBD and European Renal Nutrition working groups of the European Renal Association (ERA), together with the CKD-MBD and Dialysis working groups of the European Society for Pediatric Nephrology (ESPN), developed key evidence points and clinical practice points on calcium management in children and adults with CKD across stages of disease. These were reviewed by a Delphi panel consisting of ERA and ESPN working groups members. The main clinical practice points include a suggested total calcium intake from diet and medications of 800-1000 mg/day and not exceeding 1500 mg/day to maintain a neutral calcium balance in adults with CKD. In children with CKD, total calcium intake should be kept within the ; on behalf of European Renal Osteodystrophy (EUROD), an initiative of the Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) and the European Renal Nutrition (ERN) Working Groups of the European Renal Association (ERA) and the European Society of Pediatric Nephrology (ESPN) age-appropriate normal range. These statements provide information and may assist in decision-making, but in the absence of high-level evidence must be carefully consi