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Background Asthma is associated with impaired lung function; however, it is uncertain if a lower childhood lung function is associated with asthma onset and persistence during adolescence. The aims of the present study were to investigate the association between childhood lung function and onset and persistence of asthma during adolescence. Methods In the population-based BAMSE (Sweden), PIAMA (Netherlands) and MAAS (UK) birth cohorts, we analysed the association of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC and forced expiratory volume at 75% of FVC at age 8 years with asthma onset and persistence in adolescence (age 12–16 years) using cohort-specific logistic regression analysis followed by meta-analysis. Results In the BAMSE, PIAMA and MAAS cohorts, asthma incidence in adolescence was 6.1% (112/1824), 3.4% (36/1050) and 5.0% (39/779), respectively. Persistent asthma from childhood to adolescence was observed in 8.2%, 6.4% and 7.7% of all subjects within the respective cohorts. A higher FEV1 % predicted and FEV1/FVC at age 8 years was associated with a lower odds for adolescent-onset asthma: OR 0.98 (95% CI 0.97–1.00) and 0.97 (0.94–0.99). These associations remained significant also when restricting the analyses to subjects with no wheezing or asthma treatment in childhood. A higher FEV1/FVC at age 8 years was associated with a lower odds for asthma persistence in adolescence (0.96 (0.93–0.99)). Sex by lung function interaction analysis was not significant. Conclusions A higher lung function at school age was associated with a lower risk of adolescent-onset asthma, predominantly in males. This indicates that a lower lung function in childhood may precede and or potentially contribute to asthma incidence and persistence.

Over long stretches of the north-east coast of Qeqertarsuaq (Disko), the sediments in the Nuussuaq Basin and their relations to the volcanic rocks are concealed beneath numerous landslides. Two cores south of Qullissat drilled by Falconbridge Ltd in 1994, targeting a native-iron-bearing igneous body assumed to be a sill, present well-preserved sections through the hidden succession. We have dated the sediments in the cores palynologically. The lower part comprises 115 m of deltaic deposits, including coal seams, of the Cretaceous Atane Formation, Qilakitsoq Member (late Turonian to early Coniacian age), which has not been recorded on Disko before. The two cores and five short coastal cliff sections are mutually correlatable and correlate further to the coal seams earlier mined at Qullissat; the coals are hereby dated for the first time. The Cretaceous rocks are overlain by 15 m of marine deposits, mainly mudstones, of the Danian Eqalulik Formation, with a hiatus of c. 24 million years. The igneous body of native-iron-bearing basaltic andesite has a thick, red-oxidised, vesiculated and brecciated top zone and is interpreted as a subaerial lava flow belonging to the Asuk Member of the Vaigat Formation. The flow has run perhaps up to 20 km from the eruption site to the sea, where it ponded and attained a thickness of 138 m, the thickest lava flow in the West Greenland Basalt Group. The flow is overlain by 22 m of non-marine sandstones and mudstones of the Atanikerluk Formation. The core correlation indicates the existence of a fault with c. 90 m vertical displacement between the two drill sites. The structural relations of the various parts of the Atane Formation along the north-east coast of Disko necessitate the assumption of another hidden, prevolcanic fault south of Qullissaaqqat.

Abstract In the Arctic, the spatiotemporal variation of net methane uptake in upland soils depends on unresolved interactive controls between edaphic and microbial factors not yet included in current models, underpinning the uncertainty of upscaling the Arctic methane budget. Here we show that upland soils in Greenland are consistent methane sinks (−1.83 ± 0.19 nmol methane g−1 dw d−1) across a N-S (64–83 °N) pedoclimatic transect. We demonstrate that methane oxidizers abundance, soil pH, and available soil copper are important controls on the spatial variation in methane oxidation. We revised a soil biogeochemical model with a high-resolution land classification and meteorological data for Greenland and tested it against our methane uptake measurements. The model simulated well the magnitudes of observed methane uptake but not the spatial variation across all sites. This work provides novel insights into the controls of methane uptake, which are critical for the accuracy of methane budgets.

The Oxfordian–Ryazanian was a period of widespread deposition of marine organic-rich mudstones in basins formed during the early phases of the rifting that heralded the formation of the present-day North Atlantic. Occasionally, uninterrupted deposition prevailed for 20 million years or more. Today, mudstones of this time interval are found on the shelves bordering the North Atlantic and adjacent areas from Siberia to the Netherlands. Here, we report data on two fully cored boreholes from Wollaston Forland (North-East Greenland, approx. 74° N), which represent an uninterrupted succession from the upper Kimmeridgian to the Hauterivian. The boreholes record basin development at two different positions within an evolving halfgraben, located at the margin of the main rift, and thus partially detached from it. Although the overall depositional environment remained an oxygen-restricted deep-shelf setting, rifting-related changes can be followed through the succession. The Kimmeridgian was a period of eustatic highstand and records the incipient rifting with a transgressive trend straddling the transition to the lower Volgian by a gradual change from deposits with high levels of total organic carbon (TOC) and kerogen rich in allochthonous organic matter to deposits with lower TOC and a higher proportion of autochthonous organic matter. This is followed by a slight regressive trend with lower TOC and increased proportions of allochthonous organic matter until rifting culminated in the middle Volgian–Ryazanian, indicated by increasing autochthonous organic matter and higher TOC, which prevailed until basin ventilation occurred towards the end of the Ryazanian. The properties of the reactive kerogen fraction remained rather stable irrespective of TOC, underlining the effect of terrigenous matter input for TOC. These variations are also captured by biological markers and stable carbon isotopes. The deposits are very similar to equivalent successions elsewhere in the proto-North Atlantic region, albeit the proportion of terrigenous kerogen is greater.

Two fully cored boreholes, the Rødryggen-1 and the Brorson Halvø-1, were drilled in Wollaston Forland, North-East Greenland, in 2009 and 2010, respectively. The objective was to test the stratigraphic development of the Upper Jurassic – Lower Cretaceous mud-dominated succession in two different settings within the same fault block of a developing half-graben: centrally (Rødryggen-1 borehole) and near the uplifted crest of the rotating fault block (Brorson Halvø-1 borehole). The drilled deposits are equivalent to the principal petroleum source-rock sequence of the petroliferous basins of North-West Europe, Siberia, and basins off eastern Canada and provide a new record of an important phase of marine deoxygenation in the proto-North Atlantic region.

Two drill cores spanning the Upper Jurassic – Lower Cretaceous succession in Wollaston Forland, North-East Greenland, offer an insight into mud accumulation in an evolving distal fault block. Previous studies have revealed the presence of long-lasting black mudstone accumulation extending through the oxygen-restricted early rift and rift climax phases (Bernbjerg and Lindemans Bugt Formations). Here, we present a detailed description of the sedimentary succession extending into the late syn-rift settings (Palnatokes Bjerg and Stratumbjerg Formations). The results indicate that the Kimmeridgian – lower Volgian early rift-phase was characterised by suspension settling and millimetre-scale event deposition in a tectonically affected, prodeltaic offshore setting. The event-related depositional processes are recorded by starved wave ripples, scour-and-fill structures, putative mud-floccule ripples and mud-dominated gravity-flow deposits. During the middle Volgian – Ryazanian rift climax, the depositional environment evolved into a narrow half-graben that was detached from the proximal depocentre flanking the deltaic coastline, itself dominated by coarse sediment. The correlative sedimentary facies in the detached half-graben are bioclastic and pyrite-rich black mudstones, which document suspension settling and gravity-flow or mass-wasting deposition in sub-storm wave-base slope and basin-floor environments. Black mudstone sedimentation ended abruptly in the late Ryazanian when the accumulation of condensed, bioturbated deep marine marls coincided with broader oceanographic reorganisation concomitant with waning rift activity in the west. Deposition of red bioclastic mudstones with a common gravity-flow component characterised the Hauterivian, potentially representing final draping of the submerged fault block crest. The top of the cored succession is demarcated by dark grey bioturbated mudstones of Barremian age, reflecting the onset of regionally continuous deep marine mud accumulation in thermally subsiding basins. Although superficially monotonous, the mudstone-dominated succession reveals a highly dynamic depositional system that reflects changing sediment transport processes during almost a full rift cycle.

Abstract Accelerating biomass improvement is a major goal of Miscanthus breeding. The development and implementation of genomic‐enabled breeding tools, like marker‐assisted selection (MAS) and genomic selection, has the potential to improve the efficiency of Miscanthus breeding. The present study conducted genome‐wide association (GWA) and genomic prediction of biomass yield and 14 yield‐components traits in Miscanthus sacchariflorus. We evaluated a diversity panel with 590 accessions of M. sacchariflorus grown across 4 years in one subtropical and three temperate locations and genotyped with 268,109 single‐nucleotide polymorphisms (SNPs). The GWA study identified a total of 835 significant SNPs and 674 candidate genes across all traits and locations. Of the significant SNPs identified, 280 were localized in mapped quantitative trait loci intervals and proximal to SNPs identified for similar traits in previously reported Miscanthus studies, providing additional support for the importance of these genomic regions for biomass yield. Our study gave insights into the genetic basis for yield‐component traits in M. sacchariflorus that may facilitate marker‐assisted breeding for biomass yield. Genomic prediction accuracy for the yield‐related traits ranged from 0.15 to 0.52 across all locations and genetic groups. Prediction accuracies within the six genetic groupings of M. sacchariflorus were limited due to low sample sizes. Nevertheless, the Korea/NE China/Russia (N = 237) genetic group had the highest prediction accuracy of all genetic groups (ranging 0.26–0.71), suggesting that with adequate sample sizes, there is strong potential for genomic selection within the genetic groupings of M. sacchariflorus. This study indicated that MAS and genomic prediction will likely be beneficial for conducting population‐improvement of M. sacchariflorus.

Gestational diabetes mellitus (GDM) is associated with adverse pregnancy outcomes including large for gestational age infants. Individualizing the management of women with GDM based on the likelihood of needing insulin may improve pregnancy outcomes. The aim of this study is to identify characteristics associated with a need for insulin in women with GDM, and to develop a predictive model for insulin requirement. A historical cohort study was conducted among all women with GDM in a singleton pregnancy at Aarhus University Hospital from 2012 to 2017. Variables associated with insulin treatment were identified through multivariable logistic regression. The variables were dichotomized and included in a point scoring system aiming to predict the likelihood of needing insulin. Seven variables were associated with needing insulin: family history of diabetes, current smoker, multiparity, prepregnancy body mass index, gestational age at the oral glucose tolerance test (OGTT), 2-h glucose value at the OGTT and hemoglobin A1c at diagnosis. A risk score was calculated assigning one point to each variable. On ROC analysis, a cut-off value of ≥3 points optimally predicted a requirement for insulin. This prediction model may be clinically useful to predict requirement for insulin treatment after further validation.

Abstract Miscanthus is a genus of perennial grasses native to East Asia that shows promise as a biofuel energy source. Breeding efforts for increasing biofuel capability in this genus have focused on two species, namely M. sinensis (Msi) and M. sacchariflorus (Msa). For these efforts to succeed, it is critical that both Msi and Msa, as well as their interspecific crosses, can be grown at a wide range of latitudes. Therefore, the purpose of this study was to investigate how well existing data from Msi and Msa trials grown at locations throughout the northern hemisphere can train state‐of‐the‐art genomic selection (GS) models to predict genomic estimated breeding values (GEBVs) of dry yield for untested Msi and Msa accessions in untested environments. We found that accounting for genotype by environment interaction in the GS model did not notably improve predictive ability. Additionally, we observed that locations at lower latitudes showed higher predictive ability relative to locations at higher latitudes. These results suggest that it is crucial to increase the number of trial locations at higher latitude locations to investigate the source of this correlation. This will make it possible to train GS models using data from environments that are similar to growing conditions at the locations targeted by Msi and Msa breeders. Such an increase of trial locations in target environments could pave the way toward advancing breeding efforts for overwintering ability in Msi and Msa, and ultimately support the potential of Miscanthus as a biofuel crop.

In recent years, immune checkpoint inhibitors have proved immense clinical progression in the treatment of certain cancers. The efficacy of immune checkpoint inhibitors is correlated with mismatch repair system deficiency and is exceptionally administered based exclusively on this biological mechanism independent of the cancer type. The promising effect of immune checkpoint inhibitors has left an increasing demand for analytical tools evaluating the mismatch repair status. The analysis of microsatellite instability (MSI), reflecting an indirect but objective manner the inactivation of the mismatch repair system, plays several roles in clinical practice and, therefore, its evaluation is of high relevance. Analysis of MSI by PCR followed by fragment analysis on capillary electrophoresis remains the gold standard method for detection of a deficient mismatch repair system and thereby treatment with immune checkpoint inhibitors. Novel technologies have been applied and concepts such as tumor mutation burden have been introduced. However, to date, most of these technologies require high costs or the need of matched non-tumor tissue as internal comparator. In this study, we present a novel, one-instrument, fast, and objective method for the detection of MSI (MicroSight® MSI 1-step HRM Analysis), which does not depend on the use of matched non-tumor tissue. The assay analyzes five well-described mononucleotide microsatellite sequences by real-time PCR followed by high-resolution melt and evaluates microsatellite length variations via PCR product melting profiles. The assay was evaluated using two different patient cohorts and evaluation included several DNA extraction methodologies, two different PCR platforms, and an inter-laboratory ring study. The MicroSight® MSI assay showed a high repeatability regardless of DNA extraction method and PCR platform, and a 100% agreement of the MSI status with PCR fragment analysis methods applied as clinical comparator.

Abstract Discovery and analysis of genetic variants underlying agriculturally important traits are key to molecular breeding of crops. Reduced representation approaches have provided cost‐efficient genotyping using next‐generation sequencing. However, accurate genotype calling from next‐generation sequencing data is challenging, particularly in polyploid species due to their genome complexity. Recently developed Bayesian statistical methods implemented in available software packages, polyRAD, EBG, and updog, incorporate error rates and population parameters to accurately estimate allelic dosage across any ploidy. We used empirical and simulated data to evaluate the three Bayesian algorithms and demonstrated their impact on the power of genome‐wide association study (GWAS) analysis and the accuracy of genomic prediction. We further incorporated uncertainty in allelic dosage estimation by testing continuous genotype calls and comparing their performance to discrete genotypes in GWAS and genomic prediction. We tested the genotype‐calling methods using data from two autotetraploid species, Miscanthus sacchariflorus and Vaccinium corymbosum, and performed GWAS and genomic prediction. In the empirical study, the tested Bayesian genotype‐calling algorithms differed in their downstream effects on GWAS and genomic prediction, with some showing advantages over others. Through subsequent simulation studies, we observed that at low read depth, polyRAD was advantageous in its effect on GWAS power and limit of false positives. Additionally, we found that continuous genotypes increased the accuracy of genomic prediction, by reducing genotyping error, particularly at low sequencing depth. Our results indicate that by using the Bayesian algorithm implemented in polyRAD and continuous genotypes, we can accurately and cost‐efficiently implement GWAS and genomic prediction in polyploid crops.

Abstract Miscanthus is a high‐yielding bioenergy crop that is broadly adapted to temperate and tropical environments. Commercial cultivation of Miscanthus is predominantly limited to a single sterile triploid clone of Miscanthus × giganteus, a hybrid between Miscanthus sacchariflorus and M. sinensis. To expand the genetic base of M. × giganteus, the substantial diversity within its progenitor species should be used for cultivar improvement and diversification. Here, we phenotyped a diversity panel of 605 M. sacchariflorus from six previously described genetic groups and 27 M. × giganteus genotypes for dry biomass yield and 16 yield‐component traits, in field trials grown over 3 years at one subtropical location (Zhuji, China) and four temperate locations (Foulum, Denmark; Sapporo, Japan; Urbana, Illinois; and Chuncheon, South Korea). There was considerable diversity in yield and yield‐component traits among and within genetic groups of M. sacchariflorus, and across the five locations. Biomass yield of M. sacchariflorus ranged from 0.003 to 34.0 Mg ha−1 in year 3. Variation among the genetic groups was typically greater than within, so selection of genetic group should be an important first step for breeding with M. sacchariflorus. The Yangtze 2x genetic group (=ssp. lutarioriparius) of M. sacchariflorus had the tallest and thickest culms at all locations tested. Notably, the Yangtze 2x genetic group's exceptional culm length and yield potential were driven primarily by a large number of nodes (>29 nodes culm−1 average over all locations), which was consistent with the especially late flowering of this group. The S Japan 4x, the N China/Korea/Russia 4x, and the N China 2x genetic groups were also promising genetic resources for biomass yield, culm length, and culm thickness, especially for temperate environments. Culm length was the best indicator of yield potential in M. sacchariflorus. These results will inform breeders' selection of M. sacchariflorus genotypes for population improvement and adaptation to target production environments.

Acute mixed cellular and antibody-mediated rejection (MR) has an estimated prevalence of 7.8%. However, knowledge of MR immune pathogenesis in cardiac graft rejection remains sparse. We report a case of acute MR in a heart transplant patient with a mutation in the MYH7 gene encoding the protein β-myosin heavy chain, resulting in familial hypertrophic cardiomyopathy. The patient presented with substantial eosinophilic infiltration and extensive production of Human Leukocyte Antigen (HLA)-antibodies associated with shared epitopes. Eosinophilic infiltration in the endo- and myocardium was diagnosed in routine post-transplant biopsies stained with hematoxylin-eosin on day 6 after transplantation. On day 27, the patient presented with dyspnea, weight gain, increased pro-brain natriuretic peptide, and was hospitalized due to suspected acute rejection. Endomyocardial biopsies showed eosinophils in endo- and myocardium with additional lymphocytes and hyperplastic endothelium. Immunohistochemistry, including CD31/CD68 double stain confirmed endothelium-associated macrophages in capillaries and severe C4d positivity in the capillaries and endocardial endothelium. Lymphocytes were identified as primarily CD45+/CD3+ T cells with a concomitant few CD45+/CD20+ B cells. HLA-antibody analysis demonstrated a significant increase in 13 HLA-antibodies present in pre-transplant-serum, of which anti-B7 was donor-specific, and 23 strong de-novo HLA-class I antibodies of which anti-B62 was donor-specific. 72% of HLA-antibodies, including the two donor-specific antibodies, shared the same HLA antigen epitope; 43P+69A or 163L+167W. This is a case reporting both HLA-antibody and pathohistological data indicating the need for better understanding of interactions between cellular and antibody-mediated immune response mechanisms in graft rejection, and the significance of pre-transplant donor-specific antibodies during immunological pre-transplant risk assessment.