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The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
It has been reported that foetal death follows a seasonal pattern. Influenza virus infection has been postulated as one possible contributor to this seasonal variation. This ecological study explored the temporal association between the influenza activity and the frequency of foetal death. Time series analysis was conducted using weekly influenza-like illness consultation proportions from the Danish sentinel surveillance system and weekly proportions of spontaneous abortions and stillbirths from hospital registers from 1994 to 2009. The association was examined in an autoregressive (AR) integrated (I) moving average (MA) model and subsequently analysed with cross-correlation functions. Our findings confirmed the well-known seasonality in influenza, but also seasonality in spontaneous abortion. No clear pattern of seasonality was found for stillbirths, although the analysis exposed dependency between observations. One final AR integrated MA model was identified for the influenza-like illness (ILI) series. We found no statistically significant relationship between weekly influenza-like illness consultation proportions and weekly spontaneous abortion proportions (five lags: P = 0.52; 11 lags: P = 0.91) or weekly stillbirths (five lags: P = 0.93; 11 lags: P = 0.40). Exposure to circulating influenza during pregnancy was not associated with rates of spontaneous abortions or stillbirths. Seasonal variations in spontaneous abortion were confirmed and this phenomenon needs further investigation.
Tail damage within the production of finisher pigs is an animal welfare problem. Recent research suggests that removal of known risk factors may not be enough to eliminate tail biting, especially in undocked pigs, thus a different strategy is worth investigating. This could be early detection of tail biting, using behavioural changes observed before tail damage. If these early stages of tail biting can be detected before tail damage occurs, then tail damage could be prevented by early interventions. The first step in developing such a strategy is to identify the types of behaviour changes that emerge during early stages of tail biting. Thus, the aim of the current study was to investigate whether pen level activity and object manipulation evolved differently during the last 7 days before the scoring of tail damage (day 0) for pens scored with tail damage (tail damage pens) and pens not scored with tail damage (matched control pens). The study included video recordings for twenty-four tail damage pens and thirty-two matched control pens. Activity level and object manipulation were observed the last 7 days before day 0 during the morning (0600 to 0800 h), afternoon (1600 to 1800 h) and evening (2200 to 2400 h, only activity level). Both activity level and object manipulation were analysed using generalised linear mixed effects models with a binomial distribution for activity level and a negative binomial distribution for object manipulation. The probability of being active was higher in tail damage pens compared to control pens during the afternoon the last 5 days before day 0 (P<0.001). This was seen due to a decrease in activity level in the control pens, which makes it difficult to identify future tail damage pens from this difference. Object manipulation was lower in tail damage pens compared to the control pens on all 7 days before day 0, but only in pens with undocked pigs (P<0.01). Thus, it is still unknown when this difference in object manipulation initiated. It was concluded that both activity level and object manipulation seemed related to ongoing tail biting and should be investigated through more detailed observations and for a longer time to establish the normal behaviour pattern for a particular pen. Thus, it is suggested that future research focusses on developing automatic monitoring methods for pen level activity and object manipulation and applies algorithms that establish and detect deviations from the normal behaviour pattern of the pen before tail damage.
Piglet mortality in outdoor production systems varies across the year, and a reason for this variation could be fluctuations in hut climate, as ambient temperature might influence piglet survival, both directly and indirectly. Therefore, the aim of the current study was to investigate the impact of farrowing hut climate and year variation on stillbirth and liveborn mortality. A large-scale observational study was conducted at five commercial organic pig-producing herds in Denmark from June 2015 to August 2016. Both year variation (F3,635=4.40, P=0.004) and farrowing hut temperature (F2,511=6.46, P=0.002) affected the rate of stillbirths. The risk of stillborn piglets was lowest in winter and during this season larger changes in hut temperature between day 1 prepartum and the day of farrowing increased the risk of stillbirths (F1,99=6.39, P=0.013). In addition, during the warm part of the year stillbirth rate increased at temperatures ⩾27°C. Year variation also affected liveborn mortality (F3,561=3.86, P=0.009) with a lower rate of liveborn deaths in spring. However, the hut climate did not influence liveborn deaths. Consequently, other factors than hut climate may explain the influence of year variation on liveborn mortality. These could be light differences causing seasonality in reproduction and lactation.
Assessing the relationship between antimicrobial usage (AMU) and antimicrobial resistance (AMR) requires the accurate and precise utilisation of register data. Therefore, validation of register-based data is essential for evaluating the quality and, subsequently, the internal validity of studies based on the data.
In this study, different smoothing methods for Veterinary Medicine Statistic Program database (VetStat)-records were validated by comparing these with farm-records. Comparison between measurements included accuracy as; completeness and correctness, and precision as; a relative difference of the error, correlation with Fisher's z transformation and reliability coefficient. The most valid methods of those examined were then used in re-analyses of the abundance of AMR genes in 10 finisher batches from a previous study.
Improved accuracy was found when detailed smoothing methods were applied. Although the precision also increased, the effect was not as pronounced, as the usage estimate of all smoothing methods deviated moderately compared with the farm-registrations. Applying the most valid methods to the 10 finisher batches increased estimates of statistical model fit for aminoglycosides, lincosamides, tetracyclines and decreased estimates of statistical model fit for macrolides. The estimates of statistical model fit for sulfonamides and broad-spectrum penicillins remained the same.
Through refined data transformation, VetStat-records can be used to calculate a daily amount of AMU per pig reflecting the true usage accurately and moderately precisely, which is the foundation for calculating lifetime AMU.
Deficit irrigation (DI) improves water use efficiency (WUE), but the reduced water input often limits plant growth and nutrient uptake. The current study examined whether arbuscular mycorrhizal fungi (AMF) could alleviate abiotic stress caused by low phosphorus (P) fertilization and DI.
A greenhouse experiment was conducted with potato grown with (P1) or without (P0) P fertilization, with AMF (M1+: Rhizophagus irregularis or M2+: Glomus proliferum) or AMF-free control (M−) and subjected to full irrigation (FI), DI or partial root-zone drying (PRD).
Inoculation of M1+ and M2+ maintained or improved plant growth and P/nitrogen (N) uptake when subjected to DI/PRD and P0. However, the positive responses to AMF varied with P level and irrigation regime. Functional differences were found in ability of AMF species alleviating plant stress. The largest positive plant biomass response to M1+ and M2+ was found under FI, both at P1 and P0 (25% increase), while plant biomass response to M1+ and M2+ under DI/PRD (14% increase) was significantly smaller. The large growth response to AMF inoculation, particularly under FI, may relate to greater photosynthetic capacity and leaf area, probably caused by stimulation of plant P/N uptake and carbon partitioning toward roots and tubers. However, plant growth response to AMF was not related to the percentage of AMF root colonization. Arbuscular mycorrhizal fungi can maintain and improve P/N uptake, WUE and growth of plants both at high/low P levels and under FI/DI. If this is also the case under field conditions, it should be implemented for sustainable potato production.
The aim of this study was to validate the estimated habitual dietary intake from a newly developed web-based FFQ (WebFFQ), for use in an adult population in Norway. In total, ninety-two individuals were recruited. Total energy expenditure (TEE) measured by doubly labelled water was used as the reference method for energy intake (EI) in a subsample of twenty-nine women, and multiple 24-h recalls (24HR) were used as the reference method for the relative validation of macronutrients and food groups in the entire sample. Absolute differences, ratios, crude and deattenuated correlations, cross-classifications, Bland–Altman plot and plots between misreporting of EI (EI–TEE) and the relative misreporting of food groups (WebFFQ–24HR) were used to assess the validity. Results showed that EI on group level was not significantly different from TEE measured by doubly labelled water (0·7 MJ/d), but ranking abilities were poor (r −0·18). The relative validation showed an overestimation for the majority of the variables using absolute intakes, especially for the food groups ‘vegetables’ and ‘fish and shellfish’, but an improved agreement between the test and reference tool was observed for energy adjusted intakes. Deattenuated correlation coefficients were between 0·22 and 0·89, and low levels of grossly misclassified individuals (0–3 %) were observed for the majority of the energy adjusted variables for macronutrients and food groups. In conclusion, energy estimates from the WebFFQ should be used with caution, but the estimated absolute intakes on group level and ranking abilities seem acceptable for macronutrients and most food groups.
One challenge of intensive pig production is tail damage caused by tail biting, and farmers often decrease the prevalence of tail damage through tail docking. However, tail docking is not an optimal preventive measure against tail damage and thus, it would be preferable to replace it. The aim of the current study was to investigate the relative effect of three possible preventive measures against tail damage. The study included 112 pens with 1624 finisher pigs divided between four batches. Pens were randomly assigned to one level of each of three treatments: (1) tail-docked (n=60 pens) v. undocked (n=52 pens), (2) 150 g of straw provided per pig per day on the solid floor (n=56 pens) v. no straw provided (n=56 pens), (3) stocking density of 1.21 m2/pig (11 pig/pen; n=56 pens) v. 0.73 m2/pig (18 pigs/pen; n=56 pens). Tail damage was recorded three times per week throughout the finisher period by scoring the tail of each individual pig. A pen was recorded as a tail damage pen and no longer included in the study if at least one pig in a pen had a bleeding tail wound; thus, only the first incidence of tail damage on pen level was recorded. Data were analysed by a Cox regression for survival analysis assuming proportional hazards. Results are presented as hazards, and a higher hazard means that a pen has a higher risk of tail damage and of it happening earlier in the finisher period. Pens with undocked pigs had a 4.32-fold higher hazard of tail damage compared with pens with docked pigs (P<0.001). Pens with no straw provided had a 2.22-fold higher hazard of tail damage compared with pens with straw provided (P<0.01). No interactions was seen between the treatments, but the effect of tail docking was higher than the effect of straw provision (P<0.001). Stocking density did not have a significant effect on the hazard of tail damage (hazard rate ratios (HRR)=1.67; P=0.064). However, a combination of straw provision and lowered stocking density showed a similar hazard of tail damage as seen with only tail docking (HRR=1.58; P=0.39). In conclusion, tail docking and straw provision were preventive measures against tail damage, and tail docking reduced the risk more than straw provision. A combination of other preventive measures is necessary to reduce the risk of tail damage in undocked pigs to the same level as in docked pigs.
Physically based projections of the Greenland ice sheet contribution to future sea-level change are subject to uncertainties of the atmospheric and oceanic climatic forcing and to the formulations within the ice flow model itself. Here a higher-order, three-dimensional thermomechanical ice flow model is used, initialized to the present-day geometry. The forcing comes from a high-resolution regional climate model and from a flowline model applied to four individual marine-terminated glaciers, and results are subsequently extended to the entire ice sheet. The experiments span the next 200 years and consider climate scenario SRES A1B. The surface mass-balance (SMB) scheme is taken either from a regional climate model or from a positive-degree-day (PDD) model using temperature and precipitation anomalies from the underlying climate models. Our model results show that outlet glacier dynamics only account for 6–18% of the sea-level contribution after 200 years, confirming earlier findings that stress the dominant effect of SMB changes. Furthermore, interaction between SMB and ice discharge limits the importance of outlet glacier dynamics with increasing atmospheric forcing. Forcing from the regional climate model produces a 14–31 % higher sea-level contribution compared to a PDD model run with the same parameters as for IPCC AR4.
We assess the runoff and surface mass balance (SMB) of the Greenland ice sheet in the Nuuk region (southwest) using output of two regional climate models (RCMs) evaluated by observations. The region encompasses six glaciers that drain into Godthåbsfjord. RCM data (1960–2012) are resampled to a high spatial resolution to include the narrow (relative to the native grid spacing) glacier trunks in the ice mask. Comparing RCM gridded results with automatic weather station (AWS) point measurements reveals that locally models can underestimate ablation and overestimate accumulation by up to tens of per cent. However, comparison with lake discharge indicates that modelled regional runoff totals are more accurate. Model results show that melt and runoff in the Nuuk region have doubled over the past two decades. Regional SMB attained negative values in recent high-melt years. Taking into account frontal ablation of the marine-terminating glaciers, the region lost 10–20 km3 w.e. a–1 in 2010–12. If 2010 melting prevails during the remainder of this century, a low-end estimate of sea-level rise of 5 mm is expected by 2100 from this relatively small section (2.6%) of the ice sheet alone.
The objectives were to present three approaches for calculating antimicrobial (AM) use in pigs that take into account the rearing period and rearing site, and to study the association between these measurements and phenotypical resistance and abundance of resistance genes in faeces samples from 10 finisher batches. The AM use was calculated relative to the rearing period of the batches as (i) ‘Finisher Unit Exposure’ at unit level, (ii) ‘Lifetime Exposure’ at batch level and (iii) ‘Herd Exposure’ at herd level. A significant effect on the occurrence of tetracycline resistance measured by cultivation was identified for Lifetime Exposure for the AM class: tetracycline. Furthermore, for Lifetime Exposure for the AM classes: macrolide, broad-spectrum penicillin, sulfonamide and tetracycline use as well as Herd Unit Exposure for the AM classes: aminoglycoside, lincosamide and tetracycline use, a significant effect was observed on the occurrence of genes coding for the AM resistance classes: aminoglycoside, lincosamide, macrolide, β-lactam, sulfonamide and tetracycline. No effect was observed for Finisher Unit Exposure. Overall, the study shows that Lifetime Exposure is an efficient measurement of AM use in finisher batches, and has a significant effect on the occurrence of resistance, measured either by cultivation or metagenomics.
Background: Cerebral palsy (CP) is a debilitating disorder (1). Based on neuromotor impairments it is divided to spastic, dyskinetic and ataxic types (2). Inborn Errors of Metabolism (IEMs), monogenic and chromosomal disorders mimic CP (3). We aimed to identify causal genetic variants in patients with atypical dyskinetic CP in whom known IEMs were ruled out. Timely diagnosis is essential for proper management, especially in conditions that mimic CP and are treatable. Methods: We enrolled 23 patients with unexplained atypical dyskinetic CP, for whole exome sequencing. Variants were filtered against public and in-house databases to identify variants predicted as damaging (in silico tools and ACMG criteria). We applied a virtual gene panel of known and suspected CP and movement disorder genes and investigated each sample. Results: The participants presented with symptoms including: spasticity, dystonia, choera-athetosis, ataxia and cognitive delays. We identified 23 diagnoses: 13 dominant,6 recessive and 4 X-linked. 12 patients had movement disorders. In 4, the diagnoses enabled targeted treatment (neurotransmitter supplements in Unverricht Lundborg diseases (CSTB) and PAK3 deficiency, deep brain stimulation in GNAO1 deficiency, medical diet in Glutaric Aciduria (GCDH). Conclusions: Whole Exome Sequencing contributes to establishing diagnosis in patients with atypical dyskinetic CP resulting in precision medicine and improved health outcomes.
In a longitudinal study including 642 healthy 8–11-year-old Danish children, we investigated associations between vitamin D dependent SNP and serum 25-hydroxyvitamin D (25(OH)D) concentrations across a school year (August–June). Serum 25(OH)D was measured three times for every child, which approximated measurements in three seasons (autumn, winter, spring). Dietary and supplement intake, physical activity, BMI and parathyroid hormone were likewise measured at each time point. In all, eleven SNP in four vitamin D-related genes: Cytochrome P450 subfamily IIR1 (CYP2R1); 7-dehydrocholesterol reductase/nicotinamide adenine dinucleotide synthetase-1(DHCR7/NADSYN1); group-specific complement (GC); and vitamin D receptor were genotyped. We found minor alleles of CYP2R1 rs10500804, and of GC rs4588 and rs7041 to be associated with lower serum 25(OH)D concentrations across the three seasons (all P<0·01), with estimated 25(OH)D differences of −5·8 to −10·6 nmol/l from major to minor alleles homozygosity. In contrast, minor alleles homozygosity of rs10741657 and rs1562902 in CYP2R1 was associated with higher serum 25(OH)D concentrations compared with major alleles homozygosity (all P<0·001). Interestingly, the association between season and serum 25(OH)D concentrations was modified by GC rs7041 (Pinteraction=0·044), observed as absence of increase in serum 25(OH)D from winter to spring among children with minor alleles homozygous genotypes compared with the two other genotypes of rs7041 (P<0·001). Our results suggest that common genetic variants are associated with lower serum 25(OH)D concentrations across a school year. Potentially due to modified serum 25(OH)D response to UVB sunlight exposure. Further confirmation and paediatric studies investigating vitamin D-related health outcomes of these genotypic differences are needed.
We present a combined numerical (particle vortex method) and experimental (soap film tunnel) study of a symmetric foil undergoing prescribed oscillations in a two-dimensional free stream. We explore pure pitching and pure heaving, and contrast these two generic types of kinematics. We compare measurements and simulations when the foil is forced with pitching oscillations, and we find a close correspondence between flow visualisations using thickness variations in the soap film and the numerically determined vortex structures. Numerically, we determine wake maps spanned by oscillation frequency and amplitude, and we find qualitatively similar maps for pitching and heaving. We determine the drag–thrust transition for both pitching and heaving numerically, and we discuss it in relation to changes in wake structure. For heaving with low oscillation frequency and high amplitude, we find that the drag–thrust transition occurs in a parameter region with wakes in which two vortex pairs are formed per oscillation period, in contrast to the common transition scenario in regions with inverted von Kármán wakes.
The healthy Nordic diet has been previously shown to have health beneficial effects among subjects at risk of CVD. However, the extent of food changes needed to achieve these effects is less explored. The aim of the present study was to investigate the effects of exchanging a few commercially available, regularly consumed key food items (e.g. spread on bread, fat for cooking, cheese, bread and cereals) with improved fat quality on total cholesterol, LDL-cholesterol and inflammatory markers in a double-blind randomised, controlled trial. In total, 115 moderately hypercholesterolaemic, non-statin-treated adults (25–70 years) were randomly assigned to an experimental diet group (Ex-diet group) or control diet group (C-diet group) for 8 weeks with commercially available food items with different fatty acid composition (replacing SFA with mostly n-6 PUFA). In the Ex-diet group, serum total cholesterol (P<0·001) and LDL-cholesterol (P<0·001) were reduced after 8 weeks, compared with the C-diet group. The difference in change between the two groups at the end of the study was −9 and −11 % in total cholesterol and LDL-cholesterol, respectively. No difference in change in plasma levels of inflammatory markers (high-sensitive C-reactive protein, IL-6, soluble TNF receptor 1 and interferon-γ) was observed between the groups. In conclusion, exchanging a few regularly consumed food items with improved fat quality reduces total cholesterol, with no negative effect on levels of inflammatory markers. This shows that an exchange of a few commercially available food items was easy and manageable and led to clinically relevant cholesterol reduction, potentially affecting future CVD risk.
Glacier surface mass-balance measurements on Greenland started more than a century ago, but no compilation exists of the observations from the ablation area of the ice sheet and local glaciers. Such data could be used in the evaluation of modelled surface mass balance, or to document changes in glacier melt independently from model output. Here, we present a comprehensive database of Greenland glacier surface mass-balance observations from the ablation area of the ice sheet and local glaciers. The database spans the 123 a from 1892 to 2015, contains a total of ~3000 measurements from 46 sites, and is openly accessible through the PROMICE web portal (http://www.promice.dk). For each measurement we provide X, Y and Z coordinates, starting and ending dates as well as quality flags. We give sources for each entry and for all metadata. Two thirds of the data were collected from grey literature and unpublished archive documents. Roughly 60% of the measurements were performed by the Geological Survey of Denmark and Greenland (GEUS, previously GGU). The data cover all regions of Greenland except for the southernmost part of the east coast, but also emphasize the importance of long-term time series of which there are only two exceeding 20 a. We use the data to analyse uncertainties in point measurements of surface mass balance, as well as to estimate surface mass-balance profiles for most regions of Greenland.
Bones that have undergone burning at high temperatures (i.e. cremation) no longer contain organic carbon. Lanting et al. (2001) proposed that some of the original structural carbonate, formed during bioapatite formation, survives. This view is based on paired radiocarbon dating of cremated bone apatite and contemporary charcoal. However, stable carbon isotope composition of carbonate in cremated bones is consistently light compared to the untreated material and is closer to the δ13C values seen in C3 plant material. This raises the question of the origin of carbonate carbon in cremated bone apatite. That is, does the isotope signal reflect an exchange of carbon with the local cremation atmosphere and thus with carbon from the burning fuel, or is it caused by isotopic fractionation during cremation?
To study the changes in carbon isotopes (14C, 13C) of bone apatite during burning up to 800 °, a modern bovine bone was exposed to a continuous flow of an artificial atmosphere (basically a high-purity O2/N2 gas mix) under defined conditions (temperature, gas composition). To simulate the influence of the fuel carbon available under real cremation conditions, fossil CO2 was added at different concentrations. To yield cremated bone apatite properties similar to archaeological cremated bones, in terms of crystallographic criteria, water vapor had to be added to the atmosphere in the oven. Infrared vibrational spectra reveal large increases in crystal size and loss of carbonate upon cremation. The isotope results indicate an effective carbon exchange between bone apatite carbonate and CO2 in the combustion gases depending on temperature and CO2 concentration. 14C dates on archaeological cremated bone apatite may thus suffer from an old-wood effect. Paired 13C and 14C values indicate that in addition to this exchange, isotope fractionation between CO2 and carbonate, and admixture of carbon from other sources such as possibly collagen or atmospheric CO2, may play a role in determining the final composition of the apatite carbonate.