Did algal toxin and Klebsiella infections cause the unexplained 2007 mass mortality event in Danish and Swedish marine mammals?

An unusual mass mortality event (MME) of harbour seals (Phoca vitulina) and harbour porpoises (Phocoena phocoena) occurred in Denmark and Sweden in June 2007. Prior to this incident, the region had experienced two MMEs in harbour seals caused by Phocine Distemper Virus (PDV) in 1988 and 2002. Although epidemiology and symptoms of the 2007 MME resembled PDV, none of the animals examined for PDV tested positive. Thus, it has been speculated that another - yet unknown - pathogen caused the June 2007 MME. To shed new light on the likely cause of death, we combine previously unpublished veterinary examinations of harbour seals with novel analyses of algal toxins and algal monitoring data. All harbour seals subject to pathological examination showed pneumonia, but were negative for PDV, influenza and coronavirus. Histological analyses revealed septicaemia in multiple animals, and six animals tested positive for Klebsiella pneumonia. Furthermore, we detected the algal Dinophysis toxin DTX-1b (1-115 ng g-1) in five seals subject to toxicology, representing the first time DTX-1b has been detected in marine vertebrates. However, no animals tested positive for both Klebsiella and toxins. Thus, while our relatively small sample size prevent firm conclusions on causative agents, we speculate that the unexplained MME may have been caused by a chance incidence of multiple pathogens acting in parallel in June 2007, including Dinophysis toxin and Klebsiella. Our study illustrates the complexity of wildlife MMEs and highlights the need for thorough sampling during and after MMEs, as well as additional research on and monitoring of DTX-1b and other algal toxins in the region.

Airborne environmental DNA captures terrestrial vertebrate diversity in nature.

The current biodiversity and climate crises highlight the need for efficient tools to monitor terrestrial ecosystems. Here, we provide evidence for the use of airborne eDNA analyses as a novel method for detecting terrestrial vertebrate communities in nature. Metabarcoding of 143 airborne eDNA samples collected during 3 days in a mixed forest in Denmark yielded 64 bird, mammal, fish and amphibian taxa, of which the detected 57 'wild' taxa represent over a quarter of the around 210 terrestrial vertebrates that occur in the overall area. We provide evidence for the spatial movement and temporal patterns of airborne eDNA and for the influence of weather conditions on vertebrate detections. This study demonstrates airborne eDNA for high-resolution biomonitoring of vertebrates in terrestrial systems and elucidates its potential to guide global nature management and conservation efforts in the ongoing biodiversity crisis.

An evolutionarily distinct ringed seal in the Ilulissat Icefjord.

The Earth's polar regions are low rates of inter- and intraspecific diversification. An extreme mammalian example is the Arctic ringed seal (Pusa hispida hispida), which is assumed to be panmictic across its circumpolar Arctic range. Yet, local Inuit communities in Greenland and Canada recognize several regional variants; a finding supported by scientific studies of body size variation. It is however unclear whether this phenotypic variation reflects plasticity, morphs or distinct ecotypes. Here, we combine genomic, biologging and survey data, to document the existence of a unique ringed seal ecotype in the Ilulissat Icefjord (locally 'Kangia'), Greenland; a UNESCO World Heritage site, which is home to the most productive marine-terminating glacier in the Arctic. Genomic analyses reveal a divergence of Kangia ringed seals from other Arctic ringed seals about 240 kya, followed by secondary contact since the Last Glacial Maximum. Despite ongoing gene flow, multiple genomic regions appear under strong selection in Kangia ringed seals, including candidate genes associated with pelage coloration, growth and osmoregulation, potentially explaining the Kangia seal's phenotypic and behavioural uniqueness. The description of 'hidden' diversity and adaptations in yet another Arctic species merits a reassessment of the evolutionary processes that have shaped Arctic diversity and the traditional view of this region as an evolutionary freezer. Our study highlights the value of indigenous knowledge in guiding science and calls for efforts to identify distinct populations or ecotypes to understand how these might respond differently to environmental change.

Holocene deglaciation drove rapid genetic diversification of Atlantic walrus.

Rapid global warming is severely impacting Arctic ecosystems and is predicted to transform the abundance, distribution and genetic diversity of Arctic species, though these linkages are poorly understood. We address this gap in knowledge using palaeogenomics to examine how earlier periods of global warming influenced the genetic diversity of Atlantic walrus (Odobenus rosmarus rosmarus), a species closely associated with sea ice and shallow-water habitats. We analysed 82 ancient and historical Atlantic walrus mitochondrial genomes (mitogenomes), including now-extinct populations in Iceland and the Canadian Maritimes, to reconstruct the Atlantic walrus' response to Arctic deglaciation. Our results demonstrate that the phylogeography and genetic diversity of Atlantic walrus populations was initially shaped by the last glacial maximum (LGM), surviving in distinct glacial refugia, and subsequently expanding rapidly in multiple migration waves during the late Pleistocene and early Holocene. The timing of diversification and establishment of distinct populations corresponds closely with the chronology of the glacial retreat, pointing to a strong link between walrus phylogeography and sea ice. Our results indicate that accelerated ice loss in the modern Arctic may trigger further dispersal events, likely increasing the connectivity of northern stocks while isolating more southerly stocks putatively caught in small pockets of suitable habitat.

TNIK is a conserved regulator of glucose and lipid metabolism in obesity.

Obesity and type 2 diabetes (T2D) are growing health challenges with unmet treatment needs. Traf2- and NCK-interacting protein kinase (TNIK) is a recently identified obesity- and T2D-associated gene with unknown functions. We show that TNIK governs lipid and glucose homeostasis in Drosophila and mice. Loss of the Drosophila ortholog of TNIK, misshapen, altered the metabolite profiles and impaired de novo lipogenesis in high sugar-fed larvae. Tnik knockout mice exhibited hyperlocomotor activity and were protected against diet-induced fat expansion, insulin resistance, and hepatic steatosis. The improved lipid profile of Tnik knockout mice was accompanied by enhanced skeletal muscle and adipose tissue insulin-stimulated glucose uptake and glucose and lipid handling. Using the T2D Knowledge Portal and the UK Biobank, we observed associations of TNIK variants with blood glucose, HbA1c, body mass index, body fat percentage, and feeding behavior. These results define an untapped paradigm of TNIK-controlled glucose and lipid metabolism.

Screening for Influenza and Morbillivirus in Seals and Porpoises in the Baltic and North Sea.

Historically, the seals and harbour porpoises of the Baltic Sea and North Sea have been subjected to hunting, chemical pollutants and repeated mass mortalities, leading to significant population fluctuations. Despite the conservation implications and the zoonotic potential associated with viral disease outbreaks in wildlife, limited information is available on the circulation of viral pathogens in Baltic Sea seals and harbour porpoises. Here, we investigated the presence of the influenza A virus (IAV), the phocine distemper virus (PDV) and the cetacean morbillivirus (CeMV) in tracheal swabs and lung tissue samples from 99 harbour seals, 126 grey seals, 73 ringed seals and 78 harbour porpoises collected in the Baltic Sea and North Sea between 2002-2019. Despite screening 376 marine mammals collected over nearly two decades, we only detected one case of PDV and two cases of IAV linked to the documented viral outbreaks in seals in 2002 and 2014, respectively. Although we find no evidence of PDV and IAV during intermediate years, reports of isolated cases of PDV in North Sea harbour seals and IAV (H5N8) in Baltic and North Sea grey seals suggest introductions of those pathogens within the sampling period. Thus, to aid future monitoring efforts we highlight the need for a standardized and continuous sample collection of swabs, tissue and blood samples across Baltic Sea countries.

Fragmented habitat compensates for the adverse effects of genetic bottleneck.

In the face of the human-caused biodiversity crisis, understanding the theoretical basis of conservation efforts of endangered species and populations has become increasingly important. According to population genetics theory, population subdivision helps organisms retain genetic diversity, crucial for adaptation in a changing environment. Habitat topography is thought to be important for generating and maintaining population subdivision, but empirical cases are needed to test this assumption. We studied Saimaa ringed seals, landlocked in a labyrinthine lake and recovering from a drastic bottleneck, with additional samples from three other ringed seal subspecies. Using whole-genome sequences of 145 seals, we analyzed the distribution of variation and genetic relatedness among the individuals in relation to the habitat shape. Despite a severe history of genetic bottlenecks with prevalent homozygosity in Saimaa ringed seals, we found evidence for the population structure mirroring the subregions of the lake. Our genome-wide analyses showed that the subpopulations had retained unique variation and largely complementary patterns of homozygosity, highlighting the significance of habitat connectivity in conservation biology and the power of genomic tools in understanding its impact. The central role of the population substructure in preserving genetic diversity at the metapopulation level was confirmed by simulations. Integration of genetic analyses in conservation decisions gives hope to Saimaa ringed seals and other endangered species in fragmented habitats.

Skull ecomorphological variation of narwhals (Monodon monoceros, Linnaeus 1758) and belugas (Delphinapterus leucas, Pallas 1776) reveals phenotype of their hybrids.

Narwhals and belugas are toothed whales belonging to the Monodontidae. Belugas have a circumpolar Arctic and sub-Artic distribution while narwhals are restricted to the Atlantic Arctic. Their geographical ranges overlap during winter migrations in the Baffin Bay area (Canada/West Greenland) and successful interbreeding may occur. Here, we employed geometric morphometrics on museum specimens to explore the cranium and mandible morphology of a known hybrid (NHMD MCE 1356) and the cranium morphology of a putative hybrid (NHMD 1963.44.1.4) relative to skull morphological variation in the parental species. Specifically, we used 3D models of skulls from 69 belugas, 86 narwhals, and the two known/putative hybrids and 2D left hemi-mandibles from 20 belugas, 64 narwhals and the known hybrid. Skull shape analyses allowed clear discrimination between species. Narwhals are characterised by a relatively short rostrum and wide neurocranium while belugas show a more elongated and narrower cranium. Sexual size dimorphism was detected in narwhals, with males larger than females, but no sexual shape dimorphism was detected in either species (excluding presence/absence of tusks in narwhals). Morphological skull variation was also dependent on different allometric slopes between species and sexes in narwhals. Our analyses showed that the cranium of the known hybrid was phenotypically close to belugas but its 2D hemi-mandible had a narwhal shape and size morphology. Both cranium and mandible were strongly correlated, with the pattern of covariation being similar to belugas. The putative hybrid was a pure male narwhal with extruded teeth. Comparison of genomic DNA supported this result, and stable carbon and nitrogen isotope values suggested that the putative hybrid had a more benthic foraging strategy compared to narwhals. This work demonstrates that although the known hybrid could be discriminated from narwhals and belugas, detection of its affinities with these parental species was dependent on the part of the skull analysed.

Range-wide variation in grey seal (Halichoerus grypus) skull morphology.

The large interspecific variation in marine mammal skull and dental morphology reflects ecological specialisations to foraging and communication. At the intraspecific level, the drivers of skull shape variation are less well understood, having implications for identifying putative local foraging adaptations and delineating populations and subspecies for taxonomy, systematics, management and conservation. Here, we assess the range-wide intraspecific variation in 71 grey seal skulls by 3D surface scanning, collection of cranial landmarks and geometric morphometric analysis. We find that skull shape differs slightly between populations in the Northwest Atlantic, Northeast Atlantic and Baltic Sea. However, there was a large shape overlap between populations and variation was substantially larger among animals within populations than between. We hypothesize that this pattern of intraspecific variation in grey seal skull shape results from balancing selection or phenotypic plasticity allowing for a remarkably generalist foraging behaviour. Moreover, the large overlap in skull shape between populations implies that the separate subspecies status of Atlantic and Baltic Sea grey seals is questionable from a morphological point of view.

Using virtual reality for anatomical landmark annotation in geometric morphometrics.

To study the shape of objects using geometric morphometrics, landmarks are oftentimes collected digitally from a 3D scanned model. The expert may annotate landmarks using software that visualizes the 3D model on a flat screen, and interaction is achieved with a mouse and a keyboard. However, landmark annotation of a 3D model on a 2D display is a tedious process and potentially introduces error due to the perception and interaction limitations of the flat interface. In addition, digital landmark placement can be more time-consuming than direct annotation on the physical object using a tactile digitizer arm. Since virtual reality (VR) is designed to more closely resemble the real world, we present a VR prototype for annotating landmarks on 3D models. We study the impact of VR on annotation performance by comparing our VR prototype to Stratovan Checkpoint, a commonly used commercial desktop software. We use an experimental setup, where four operators placed six landmarks on six grey seal (Halichoerus grypus) skulls in six trials for both systems. This enables us to investigate multiple sources of measurement error. We analyse both for the configuration and for single landmarks. Our analysis shows that annotation in VR is a promising alternative to desktop annotation. We find that annotation precision is comparable between the two systems, with VR being significantly more precise for one of the landmarks. We do not find evidence that annotation in VR is faster than on the desktop, but it is accurate.

In the Search of Marine Pestiviruses: First Case of Phocoena Pestivirus in a Belt Sea Harbour Porpoise.

Pestiviruses are widespread pathogens causing severe acute and chronic diseases among terrestrial mammals. Recently, Phocoena pestivirus (PhoPeV) was described in harbour porpoises (Phocoena phocoena) of the North Sea, expanding the host range to marine mammals. While the role of the virus is unknown, intrauterine infections with the most closely related pestiviruses- Bungowannah pestivirus (BuPV) and Linda virus (LindaV)-can cause increased rates of abortions and deaths in young piglets. Such diseases could severely impact already vulnerable harbour porpoise populations. Here, we investigated the presence of PhoPeV in 77 harbour porpoises, 277 harbour seals (Phoca vitulina), grey seals (Halichoerus grypus) and ringed seals (Pusa hispida) collected in the Baltic Sea region between 2002 and 2019. The full genome sequence of a pestivirus was obtained from a juvenile female porpoise collected along the coast of Zealand in Denmark in 2011. The comparative Bayesian phylogenetic analyses revealed a close relationship between the new PhoPeV sequence and previously published North Sea sequences with a recent divergence from genotype 1 sequences between 2005 and 2009. Our findings provide further insight into the circulation of PhoPeV and expand the distribution from the North Sea to the Baltic Sea region with possible implications for the vulnerable Belt Sea and endangered Baltic Proper harbour porpoise populations.

Origin and expansion of the world's most widespread pinniped: Range-wide population genomics of the harbour seal (Phoca vitulina).

The harbour seal (Phoca vitulina) is the most widely distributed pinniped, occupying a wide variety of habitats and climatic zones across the Northern Hemisphere. Intriguingly, the harbour seal is also one of the most philopatric seals, raising questions as to how it colonized its current range. To shed light on the origin, remarkable range expansion, population structure and genetic diversity of this species, we used genotyping-by-sequencing to analyse ~13,500 biallelic single nucleotide polymorphisms from 286 individuals sampled from 22 localities across the species' range. Our results point to a Northeast Pacific origin of the harbour seal, colonization of the North Atlantic via the Canadian Arctic, and subsequent stepping-stone range expansions across the North Atlantic from North America to Europe, accompanied by a successive loss of genetic diversity. Our analyses further revealed a deep divergence between modern North Pacific and North Atlantic harbour seals, with finer-scale genetic structure at regional and local scales consistent with strong philopatry. The study provides new insights into the harbour seal's remarkable ability to colonize and adapt to a wide range of habitats. Furthermore, it has implications for current harbour seal subspecies delineations and highlights the need for international and national red lists and management plans to ensure the protection of genetically and demographically isolated populations.

Airborne environmental DNA for terrestrial vertebrate community monitoring.

Biodiversity monitoring at the community scale is a critical element of assessing and studying species distributions, ecology, diversity, and movements, and it is key to understanding and tracking environmental and anthropogenic effects on natural ecosystems.1-4 Vertebrates in terrestrial ecosystems are experiencing extinctions and declines in both population numbers and sizes due to increasing threats from human activities and environmental change.5-8 Terrestrial vertebrate monitoring using existing methods is generally costly and laborious, and although environmental DNA (eDNA) is becoming the tool of choice to assess biodiversity, few sample types effectively capture terrestrial vertebrate diversity. We hypothesized that eDNA captured from air could allow straightforward collection and characterization of terrestrial vertebrate communities. We filtered air at three localities in the Copenhagen Zoo: a stable, outside between the outdoor enclosures, and in the Rainforest House. Through metabarcoding of airborne eDNA, we detected 49 vertebrate species spanning 26 orders and 37 families: 30 mammal, 13 bird, 4 fish, 1 amphibian, and 1 reptile species. These spanned animals kept at the zoo, species occurring in the zoo surroundings, and species used as feed in the zoo. The detected species comprise a range of taxonomic orders and families, sizes, behaviors, and abundances. We found shorter distance to the air sampling device and higher animal biomass to increase the probability of detection. We hereby show that airborne eDNA can offer a fundamentally new way of studying and monitoring terrestrial communities.

Longitudinal analysis of pinnipeds in the northwest Atlantic provides insights on endemic circulation of phocine distemper virus.

Phocine distemper virus (PDV) is a morbillivirus that circulates within pinnipeds in the North Atlantic. PDV has caused two known unusual mortality events (UMEs) in western Europe (1988, 2002), and two UMEs in the northwest Atlantic (2006, 2018). Infrequent cross-species transmission and waning immunity are believed to contribute to periodic outbreaks with high mortality in western Europe. The viral ecology of PDV in the northwest Atlantic is less well defined and outbreaks have exhibited lower mortality than those in western Europe. This study sought to understand the molecular and ecological processes underlying PDV infection in eastern North America. We provide phylogenetic evidence that PDV was introduced into northwest Atlantic pinnipeds by a single lineage and is now endemic in local populations. Serological and viral screening of pinniped surveillance samples from 2006 onward suggest there is continued circulation of PDV outside of UMEs among multiple species with and without clinical signs. We report six full genome sequences and nine partial sequences derived from harbour and grey seals in the northwest Atlantic from 2011 through 2018, including a possible regional variant. Work presented here provides a framework towards greater understanding of how recovering populations and shifting species may impact disease transmission.

Emergence and radiation of distemper viruses in terrestrial and marine mammals.

Canine distemper virus (CDV) and phocine distemper virus (PDV) are major pathogens to terrestrial and marine mammals. Yet little is known about the timing and geographical origin of distemper viruses and to what extent it was influenced by environmental change and human activities. To address this, we (i) performed the first comprehensive time-calibrated phylogenetic analysis of the two distemper viruses, (ii) mapped distemper antibody and virus detection data from marine mammals collected between 1972 and 2018, and (iii) compiled historical reports on distemper dating back to the eighteenth century. We find that CDV and PDV diverged in the early seventeenth century. Modern CDV strains last shared a common ancestor in the nineteenth century with a marked radiation during the 1930s-1950s. Modern PDV strains are of more recent origin, diverging in the 1970s-1980s. Based on the compiled information on distemper distribution, the diverse host range of CDV and basal phylogenetic placement of terrestrial morbilliviruses, we hypothesize a terrestrial CDV-like ancestor giving rise to PDV in the North Atlantic. Moreover, given the estimated timing of distemper origin and radiation, we hypothesize a prominent role of environmental change such as the Little Ice Age, and human activities like globalization and war in distemper virus evolution.

Speciation in the deep: genomics and morphology reveal a new species of beaked whale Mesoplodon eueu.

The deep sea has been described as the last major ecological frontier, as much of its biodiversity is yet to be discovered and described. Beaked whales (ziphiids) are among the most visible inhabitants of the deep sea, due to their large size and worldwide distribution, and their taxonomic diversity and much about their natural history remain poorly understood. We combine genomic and morphometric analyses to reveal a new Southern Hemisphere ziphiid species, Ramari's beaked whale, Mesoplodon eueu, whose name is linked to the Indigenous peoples of the lands from which the species holotype and paratypes were recovered. Mitogenome and ddRAD-derived phylogenies demonstrate reciprocally monophyletic divergence between M. eueu and True's beaked whale (M. mirus) from the North Atlantic, with which it was previously subsumed. Morphometric analyses of skulls also distinguish the two species. A time-calibrated mitogenome phylogeny and analysis of two nuclear genomes indicate divergence began circa 2 million years ago (Ma), with geneflow ceasing 0.35-0.55 Ma. This is an example of how deep sea biodiversity can be unravelled through increasing international collaboration and genome sequencing of archival specimens. Our consultation and involvement with Indigenous peoples offers a model for broadening the cultural scope of the scientific naming process.

Measurement error using a SeeMaLab structured light 3D scanner against a Microscribe 3D digitizer.

BACKGROUND: Geometric morphometrics is a powerful approach to capture and quantify morphological shape variation. Both 3D digitizer arms and structured light surface scanners are portable, easy to use, and relatively cheap, which makes these two capturing devices obvious choices for geometric morphometrics. While digitizer arms have been the "gold standard", benefits of having full 3D models are manifold. We assessed the measurement error and investigate bias associated with the use of an open-source, high-resolution structured light scanner called SeeMaLab against the popular Microscribe 3D digitizer arm. METHODOLOGY: The analyses were based on 22 grey seal (Halichoerus grypus) skulls. 31 fixed anatomical landmarks were annotated both directly using a Microscribe 3D digitizer and on reconstructed 3D digital models created from structured light surface scans. Each skull was scanned twice. Two operators annotated the landmarks, each twice on all the skulls and 3D models, allowing for the investigation of multiple sources of measurement error. We performed multiple Procrustes ANOVAs to compare the two devices in terms of within- and between-operator error, to quantify the measurement error induced by device, to compare between-device error with other sources of variation, and to assess the level of scanning-related error. We investigated the presence of general shape bias due to device and operator. RESULTS: Similar precision was obtained with both devices. If landmarks that were identified as less clearly defined and thus harder to place were omitted, the scanner pipeline would achieve higher precision than the digitizer. Between-operator error was biased and seemed to be smaller when using the scanner pipeline. There were systematic differences between devices, which was mainly driven by landmarks less clearly defined. The factors device, operator and landmark replica were all statistically significant and of similar size, but were minor sources of total shape variation, compared to the biological variation among grey seal skulls. The scanning-related error was small compared to all other error sources. CONCLUSIONS: As the scanner showed precision similar to the digitizer, a scanner should be used if the advantages of obtaining detailed 3D models of a specimen are desired. To obtain high precision, a pre-study should be conducted to identify difficult landmarks. Due to the observed bias, data from different devices and/or operators should not be combined when the expected biological variation is small, without testing the landmarks for repeatability across platforms and operators. For any study necessitating the combination of landmark measurements from different operators, the scanner pipeline will be better suited. The small scanning-related error indicates that by following the same scanning protocol, different operators can be involved in the scanning process without introducing significant error.

Predicting sample success for large-scale ancient DNA studies on marine mammals.

In recent years, nonhuman ancient DNA studies have begun to focus on larger sample sizes and whole genomes, offering the potential to reveal exciting and hitherto unknown answers to ongoing biological and archaeological questions. However, one major limitation to such studies is the substantial financial and time investments still required during sample screening, due to uncertainty regarding successful sample selection. This study investigates the effect of a wide range of sample properties including latitude, sample age, skeletal element, collagen preservation, and context on endogenous content and DNA damage profiles for 317 ancient and historic pinniped samples collected from across the North Atlantic and surrounding regions. Using generalised linear and mixed-effect models, we found that a range of factors affected DNA preservation within each of the species under consideration. The most important findings were that endogenous content varied significantly within species according to context, the type of skeletal element, the collagen content and collection year. There also appears to be an effect of the sample's geographic origin, with samples from the Arctic generally showing higher endogenous content and lower damage rates. Both latitude and sample age were found to have significant relationships with damage levels, but only for walrus samples. Sex, ontogenetic age and extraction material preparation were not found to have any significant relationship with DNA preservation. Overall, skeletal element and sample context were found to be the most influential factors and should therefore be considered when selecting samples for large-scale ancient genome studies.

Risk factors and lifelong impact of community-acquired pneumonia in congenital heart disease.

INTRODUCTION: The prevalence of congenital heart disease (CHD) in adults is rising necessitating a greater understanding of acquired diseases such as community-acquired pneumonia, which remains a leading cause of age-related mortality and morbidity in the general population. We hypothesise that the CHD population, given cardiopulmonary mechanics and altered immune function, bears a uniquely high risk for pneumonia-related hospitalisations and mortality. METHODS: A countrywide cohort study was performed to calculate the relative risk and cumulative incidence of pneumonia hospitalisations and resultant 30-day mortality amongst the adult CHD population, matched 1:10 with non-CHD persons by gender, age, and adjusted for comorbidities. Cox proportional hazard regression quantified the impact of CHD severity and extracardiac defects. RESULTS: The CHD cohort includes 17,162 adults. The majority demonstrate mild/moderate CHD complexity. The cumulative incidence of pneumonia hospitalisation was higher for adults with CHD (hazard ratio 1.90; 95% confidence interval: 1.74-2.06) than the comparison cohort. This risk was increased for those with extracardiac defects or a syndrome (hazard ratio: 4.34; 95% confidence interval: 3.39-5.54). Additionally, CHD individuals with severe/univentricular subtypes demonstrate a heightened risk compared to the non-CHD cohort (hazard ratio: 2.35; 95% confidence interval: 1.94-2.84), as well as compared to those with mild/moderate CHD (hazard ratio: 1.28; 95% confidence interval: 1.07-1.53). In addition, pneumonia hospitalisation mortality was elevated above the comparison population with a 30-day mortality rate ratio of 1.31 (95% confidence interval: 1.00-1.73). CONCLUSION: Adults with CHD are at elevated risk of pneumonia hospitalisations and pneumonia-associated mortality. This risk is further elevated in those with severe CHD and extracardiac defects.

Physical Activity as an Effect Modifier of the Association Between Obesity and Venous Thromboembolism: A Danish Population-Based Cohort Study.

PURPOSE: Obesity is an established risk factor for venous thromboembolism (VTE), while studies on physical inactivity and VTE risk show conflicting results. We examined whether physical activity modified the association between obesity and VTE. PATIENTS AND METHODS: We conducted a population-based cohort study by combining data on outcome diagnoses, comorbidities and medication from nationwide registries with self-reported lifestyle data from an extensive Danish lifestyle questionnaire (2001-2015). We computed incidence rates (IRs) and hazard ratios (HRs) of VTE for categories of body mass index (BMI), among the total study population (n=57,523) and for physically active (n=25,387) and inactive individuals (n=30,902) separately. RESULTS: Obesity (BMI ≥30 kg/m2) was as expected associated with increased VTE risk compared with normal weight (HR 1.62, 95% confidence interval (CI): 1.26-2.09). Independent of BMI category, the rate of VTE was higher for inactive than active individuals. Thus, among obese individuals, the IR per 1000 person-years was 2.03 (95% CI: 1.60-2.57) for inactive and 1.44 (95% CI: 0.97-2.15) for active individuals. In contrast, the HR for VTE comparing obese with normal weight individuals were higher for active (HR 2.19, 95% CI: 1.35-3.58) than inactive individuals (HR 1.36, 95% CI: 1.00-1.84). CONCLUSION: Physical activity acts as an effect measure modifier of the association between obesity and VTE. Thus, physical activity reduced the absolute rate of VTE among obese individuals but increased the relative rate of VTE among obese compared with normal weight individuals.