Enthesitis in a European registry-based cohort of patients with psoriatic arthritis treated with tumour necrosis factor inhibitors: clinical burden, patient-reported outcomes, and treatment response.

OBJECTIVE: To explore the registration of enthesitis among biologic-naïve patients with psoriatic arthritis (PsA) initiating tumour necrosis factor inhibitor (TNFi) treatment across 12 European registries, compare the disease burden and patient-reported outcomes (PROs) between patients with and without enthesitis, and assess the enthesitis treatment response. METHOD: Demographics, clinical characteristics, and PROs at first TNFi (TNFi-1) initiation (baseline) were assessed in patients with PsA, diagnosed by a rheumatologist, with versus without assessment of entheses and between those with versus without enthesitis. Enthesitis scores and resolution frequency were identified at follow-up. RESULTS: Of 10 547 patients in the European Spondyloarthritis (EuroSpA) Research Collaboration Network initiating TNFi, 1357 underwent evaluation for enthesitis. Eight registries included a validated scoring system for enthesitis. At baseline, 874 patients underwent entheses assessment [Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) 485 patients, Spondyloarthritis Research Consortium of Canada (SPARCC) 389 patients]. Enthesitis was detected by MASES in 170/485 (35%, mean score ± sd 3.1 ± 2.4) and by SPARCC in 236/389 (61%, 4 ± 3.4). Achilles enthesitis was most frequent, by both MASES (unilateral/bilateral 28%/9%) and SPARCC (48%/18%). MASES/SPARCC baseline and follow-up scores for TNFi-1 were available for 100/105 patients. Of these, 63 patients (63%) (MASES) and 46 (43.8%) (SPARCC) achieved resolution of enthesitis. The site-specific enthesitis resolution was overall lower at SPARCC sites (peripheral; 63-80%) than at MASES sites (mainly axial; 82-100%) following TNFi-1. Disease activity and PROs were worse in patients with versus without enthesitis. CONCLUSION: Entheseal assessments are only registered in a minority of patients with PsA in routine care. When assessed, enthesitis was common, and a substantial proportion demonstrated resolution following treatment with TNFi-1.

Cardiovascular function in 8- to 9-year-old singletons born after ART with frozen and fresh embryo transfer.

STUDY QUESTION: Do 8- to 9-year-old singletons conceived after frozen embryo transfer (FET) or fresh embryo transfer (Fresh-ET) have increased arterial stiffness compared to naturally conceived (NC) children? SUMMARY ANSWER: The process of FET or Fresh-ET is not associated with altered cardiovascular function in 8- to 9-year-old singletons, including arterial stiffness, as compared to NC children. WHAT IS KNOWN ALREADY: ART has been suggested to influence cardiovascular risk factors (i.e. endothelial dysfunction, increased arterial blood pressure and insulin resistance). It is not known if ART procedures alter arterial stiffness in singletons. STUDY DESIGN, SIZE, DURATION: A cohort study was carried out, including 8- to 9-year-old singletons conceived after FET, Fresh-ET and NC children (50 children in each group). This study was conducted between November 2018 and August 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS: In total, 150 singletons were identified through the Danish IVF Registry and the Medical Birth Registry. They underwent cardiac magnetic resonance imaging (CMR) and anthropometric measurements. Parental data were collected using questionnaires. NC children were matched by sex and birth year with FET/Fresh-ET children. Exclusion criteria were congenital heart disease, maternal gestational diabetes or maternal diabetes mellitus. Our primary outcome was arterial stiffness, which is assessed from noninvasive arterial blood pressure and aortic ascendens distensibility. The secondary outcome was the pulse wave velocity of total aorta and exploratory outcomes were left ventricular ejection fraction, mean arterial pressure, cardiac output and total peripheral resistance. Measurements and analyses were performed blinded to the child group. MAIN RESULTS AND THE ROLE OF CHANCE: Aortic ascendens distensibility of children conceived after FET and Fresh-ET did not differ from NC children (mean (SD): FET 11.1 (3.6) 10-3 mmHg-1, Fresh-ET 11.8 (3.0) 10-3 mmHg-1, NC 11.4 (2.8) 10-3 mmHg-1, P > 0.05). Multivariate linear regression was performed to adjust for potential confounders (i.e. child sex and age, maternal BMI at early pregnancy and maternal educational level). Data showed no statistically significant differences between study groups and aortic ascendens distensibility. However, the fully adjusted model showed a non-significant tendency of lowered aortic ascendens distensibility in children born after FET compared to Fresh-ET (ß estimate (95% CI): -0.99 10-3 mmHg-1 (-2.20; 0.21)) and NC children (ß estimate (95% CI): -0.77 10-3 mmHg-1 (-1.98; 0.44)). Lastly, secondary and exploratory outcomes did not differ between the groups. Primary and secondary outcomes showed good intra-rater reliability. LIMITATIONS, REASONS FOR CAUTION: This study is possibly limited by potential selection bias as the participation rate was higher in the ART compared to the NC group. Also, in some variables, the study groups differed slightly from the non-participant population. The non-participant population (n = 1770) included those who were excluded, not invited to CMR scan, or declined to participate in this study. WIDER IMPLICATIONS OF THE FINDINGS: Our findings indicate that children born after FET or Fresh-ET do not have altered cardiovascular function, including arterial stiffness. This is reassuring for the future use of ART. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the Novo Nordisk Foundation (grant reference number: NNF19OC0054340) and The Research Foundation of Rigshospitalet. All authors declared no conflict of interests. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier: NCT03719703.

The contribution of global aviation to anthropogenic climate forcing for 2000 to 2018.

Global aviation operations contribute to anthropogenic climate change via a complex set of processes that lead to a net surface warming. Of importance are aviation emissions of carbon dioxide (CO2), nitrogen oxides (NOx), water vapor, soot and sulfate aerosols, and increased cloudiness due to contrail formation. Aviation grew strongly over the past decades (1960-2018) in terms of activity, with revenue passenger kilometers increasing from 109 to 8269 billion km yr-1, and in terms of climate change impacts, with CO2 emissions increasing by a factor of 6.8 to 1034 Tg CO2 yr-1. Over the period 2013-2018, the growth rates in both terms show a marked increase. Here, we present a new comprehensive and quantitative approach for evaluating aviation climate forcing terms. Both radiative forcing (RF) and effective radiative forcing (ERF) terms and their sums are calculated for the years 2000-2018. Contrail cirrus, consisting of linear contrails and the cirrus cloudiness arising from them, yields the largest positive net (warming) ERF term followed by CO2 and NOx emissions. The formation and emission of sulfate aerosol yields a negative (cooling) term. The mean contrail cirrus ERF/RF ratio of 0.42 indicates that contrail cirrus is less effective in surface warming than other terms. For 2018 the net aviation ERF is +100.9 milliwatts (mW) m-2 (5-95% likelihood range of (55, 145)) with major contributions from contrail cirrus (57.4 mW m-2), CO2 (34.3 mW m-2), and NOx (17.5 mW m-2). Non-CO2 terms sum to yield a net positive (warming) ERF that accounts for more than half (66%) of the aviation net ERF in 2018. Using normalization to aviation fuel use, the contribution of global aviation in 2011 was calculated to be 3.5 (4.0, 3.4) % of the net anthropogenic ERF of 2290 (1130, 3330) mW m-2. Uncertainty distributions (5%, 95%) show that non-CO2 forcing terms contribute about 8 times more than CO2 to the uncertainty in the aviation net ERF in 2018. The best estimates of the ERFs from aviation aerosol-cloud interactions for soot and sulfate remain undetermined. CO2-warming-equivalent emissions based on global warming potentials (GWP* method) indicate that aviation emissions are currently warming the climate at approximately three times the rate of that associated with aviation CO2 emissions alone. CO2 and NOx aviation emissions and cloud effects remain a continued focus of anthropogenic climate change research and policy discussions.

Polycystic ovary syndrome and offspring risk of congenital heart defects: a nationwide cohort study.

STUDY QUESTION: Is maternal polycystic ovary syndrome (PCOS) associated with increased offspring risk of congenital heart defects? SUMMARY ANSWER: This study does not support a strong association between PCOS and an increased risk of congenital heart defects. WHAT IS KNOWN ALREADY: In addition to affecting reproductive health, PCOS may involve insulin resistance. Maternal pregestational diabetes is associated with an increased risk of congenital heart defects and therefore PCOS may increase the risk of congenital heart defects in the offspring. STUDY DESIGN, SIZE, DURATION: In this nationwide cohort study, we used data from Danish health registers collected from 1995 to 2018. The study included 1 302 648 offspring and their mothers. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were live singleton offspring born during the study period. Information on maternal PCOS and offspring congenital heart defects was obtained from the National Patient Register. Logistic regression analysis was used to compute prevalence (odds) ratio (PR) of the association between PCOS and offspring congenital heart defects. MAIN RESULTS AND THE ROLE OF CHANCE: Among 1 302 648 live-born singletons, 11 804 had a mother with PCOS. Of these, 143 offspring had a congenital heart defect (prevalence 121 per 10 000) as compared with 12 832 among mothers without PCOS (prevalence 99 per 10 000). The adjusted PR was 1.22, 95% CI 1.03-1.44 comparing prevalence of congenital heart defects in offspring of women with PCOS with offspring of women without. After adjusting for the potentially mediating effect of pregestational diabetes, the PR was 1.16, 95% CI 0.98-1.37. LIMITATIONS, REASONS FOR CAUTION: PCOS may be underdetected in the National Patient Register. However, we expect that the mothers that we identified with PCOS truly had PCOS, thus, the estimated associations are not likely to be affected by this misclassification. The study does not provide evidence to rule out a moderate or weak association. WIDER IMPLICATIONS OF THE FINDINGS: These findings provide reassurance to clinicians counselling pregnant women with PCOS that the disease does not pose a markedly increased risk of offspring congenital heart defects. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by the Novo Nordisk Foundation. M.L. reports personal fees from Dansk Lægemiddel Information A/S outside the submitted work. The remaining authors have no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Competition between Allowed and First-Forbidden ß Decay: The Case of

The ß decay of ^{208}Hg into the one-proton hole, one neutron-particle _{81}^{208}Tl_{127} nucleus was investigated at CERN-ISOLDE. Shell-model calculations describe well the level scheme deduced, validating the proton-neutron interactions used, with implications for the whole of the N>126, Z<82 quadrant of neutron-rich nuclei. While both negative and positive parity states with spin 0 and 1 are expected within the Q_{ß} window, only three negative parity states are populated directly in the ß decay. The data provide a unique test of the competition between allowed Gamow-Teller and Fermi, and first-forbidden ß decays, essential for the understanding of the nucleosynthesis of heavy nuclei in the rapid neutron capture process. Furthermore, the observation of the parity changing 0^{+}→0^{-}ß decay where the daughter state is core excited is unique, and can provide information on mesonic corrections of effective operators.

Genome-wide association studies for the concentrations of insulin, triiodothyronine, and thyroxine in Chinese Holstein cattle.

To further understand the genetic structure that is associated with insulin (INS) and thyroid hormones (TH), including triiodothyronine (T3) and thyroxine (T4), in Chinese Holstein cows, we conducted a genome-wide association study (GWAS) of thyroid hormones and insulin in cows. We conducted GWAS analysis on 1217 Chinese Holstein cows raised in southern China and found 19 significant single nucleotide polymorphisms (SNPs) in this study: 10 SNPs were associated with INS, 5 SNPs were associated with T3, and 4 SNPs were associated with T4. In our study, the GWAS method was used for preliminary screening on related genes of traits, and due to insufficient relevant literature, a functional analysis of genes could only be based on human studies. We observed that DGKB from Bos taurus chromosome (BTA)4 is strongly associated with insulin secretion. We found that EXOC4 gene was significantly correlated with T3 and T4 traits. Another significant SNP was located in the CYP7A1 gene, which has been confirmed to be affected by thyroid hormones.

Genome-wide association study identifies loci linked to serum electrolyte traits in Chinese Holstein cattle.

We aimed to identify QTL for serum electrolyte traits by performing a GWAS of calcium, chloride, sodium, potassium and magnesium ion concentrations in Chinese Holstein cattle. We detected five SNPs that had significant associations with calcium ion concentrations and identified GATA2 from Bos taurus chromosome (BTA)22 as having the highest significance. Among the genes with significant results, we speculate that TMEM123 might be related to calcium channel proteins according to the functions of the TMEM family.

First Accurate Normalization of the ß-delayed α Decay of

The ^{12}C(α,γ)^{16}O reaction plays a central role in astrophysics, but its cross section at energies relevant for astrophysical applications is only poorly constrained by laboratory data. The reduced α width, γ_{11}, of the bound 1^{-} level in ^{16}O is particularly important to determine the cross section. The magnitude of γ_{11} is determined via sub-Coulomb α-transfer reactions or the ß-delayed α decay of ^{16}N, but the latter approach is presently hampered by the lack of sufficiently precise data on the ß-decay branching ratios. Here we report improved branching ratios for the bound 1^{-} level [b_{ß,11}=(5.02±0.10)×10^{-2}] and for ß-delayed α emission [b_{ßα}=(1.59±0.06)×10^{-5}]. Our value for b_{ßα} is 33% larger than previously held, leading to a substantial increase in γ_{11}. Our revised value for γ_{11} is in good agreement with the value obtained in α-transfer studies and the weighted average of the two gives a robust and precise determination of γ_{11}, which provides significantly improved constraints on the ^{12}C(α,γ) cross section in the energy range relevant to hydrostatic He burning.

Short communication: Improving the accuracy of genomic prediction of body conformation traits in Chinese Holsteins using markers derived from high-density marker panels.

This study investigated the efficiency of genomic prediction with adding the markers identified by genome-wide association study (GWAS) using a data set of imputed high-density (HD) markers from 54K markers in Chinese Holsteins. Among 3,056 Chinese Holsteins with imputed HD data, 2,401 individuals born before October 1, 2009, were used for GWAS and a reference population for genomic prediction, and the 220 younger cows were used as a validation population. In total, 1,403, 1,536, and 1,383 significant single nucleotide polymorphisms (SNP; false discovery rate at 0.05) associated with conformation final score, mammary system, and feet and legs were identified, respectively. About 2 to 3% genetic variance of 3 traits was explained by these significant SNP. Only a very small proportion of significant SNP identified by GWAS was included in the 54K marker panel. Three new marker sets (54K+) were herein produced by adding significant SNP obtained by linear mixed model for each trait into the 54K marker panel. Genomic breeding values were predicted using a Bayesian variable selection (BVS) model. The accuracies of genomic breeding value by BVS based on the 54K+ data were 2.0 to 5.2% higher than those based on the 54K data. The imputed HD markers yielded 1.4% higher accuracy on average (BVS) than the 54K data. Both the 54K+ and HD data generated lower bias of genomic prediction, and the 54K+ data yielded the lowest bias in all situations. Our results show that the imputed HD data were not very useful for improving the accuracy of genomic prediction and that adding the significant markers derived from the imputed HD marker panel could improve the accuracy of genomic prediction and decrease the bias of genomic prediction.

Longitudinal changes in brain morphology from 4 weeks to 12 months after mild traumatic brain injury: Associations with cognitive functions and clinical variables.

OBJECTIVE: To investigate longitudinal changes in cortical and subcortical volumes in patients with mild traumatic brain injury (MTBI) and to evaluate whether such changes were associated with self-reported post-concussive symptoms, global functional outcomes and neuropsychological functioning. METHODS: This was a prospecitve, longitudinal cohort study of patients with complicated (i.e presence of intracranial abnormalities on the day of injury CT) and uncomplicated MTBI (i.e, absence of intracranial abnormalities). Magnetic resonance imaging (MRI) was performed at approximately 4 weeks and 12 months. We utilized a 3T MRI system, cortical reconstruction and volumetric segmentation by FreeSurfer software. We included 33 patients with uncomplicated and 29 with complicated MTBI, who were aged 16-65 years. RESULTS: 12 months after MTBI, significant within-group volume reductions were detected in the left accumbens area and right caudate nucleus for both patients groups, but no significant differences between the groups were revealed. No associations between volumetric variables and post-concussive symptoms or global functioning were found. The left temporal thickness was significantly associated with executive functioning. CONCLUSION: Structural subcortical alterations occur after complicated and uncomplicated MTBIs but these findings were not associated with symptoms burden or functional outcomes. Nonetheless, worse executive functioning was found in patients with shrinkage of the left temporal lobe.

Prediction and validation of residual feed intake and dry matter intake in Danish lactating dairy cows using mid-infrared spectroscopy of milk.

The present study explored the effectiveness of Fourier transform mid-infrared (FT-IR) spectral profiles as a predictor for dry matter intake (DMI) and residual feed intake (RFI). The partial least squares regression method was used to develop the prediction models. The models were validated using different external test sets, one randomly leaving out 20% of the records (validation A), the second randomly leaving out 20% of cows (validation B), and a third (for DMI prediction models) randomly leaving out one cow (validation C). The data included 1,044 records from 140 cows; 97 were Danish Holstein and 43 Danish Jersey. Results showed better accuracies for validation A compared with other validation methods. Milk yield (MY) contributed largely to DMI prediction; MY explained 59% of the variation and the validated model error root mean square error of prediction (RMSEP) was 2.24kg. The model was improved by adding live weight (LW) as an additional predictor trait, where the accuracy R2 increased from 0.59 to 0.72 and error RMSEP decreased from 2.24 to 1.83kg. When only the milk FT-IR spectral profile was used in DMI prediction, a lower prediction ability was obtained, with R2=0.30 and RMSEP=2.91kg. However, once the spectral information was added, along with MY and LW as predictors, model accuracy improved and R2 increased to 0.81 and RMSEP decreased to 1.49kg. Prediction accuracies of RFI changed throughout lactation. The RFI prediction model for the early-lactation stage was better compared with across lactation or mid- and late-lactation stages, with R2=0.46 and RMSEP=1.70. The most important spectral wavenumbers that contributed to DMI and RFI prediction models included fat, protein, and lactose peaks. Comparable prediction results were obtained when using infrared-predicted fat, protein, and lactose instead of full spectra, indicating that FT-IR spectral data do not add significant new information to improve DMI and RFI prediction models. Therefore, in practice, if full FT-IR spectral data are not stored, it is possible to achieve similar DMI or RFI prediction results based on standard milk control data. For DMI, the milk fat region was responsible for the major variation in milk spectra; for RFI, the major variation in milk spectra was within the milk protein region.

Genetic parameters for fur quality graded on live animals and dried pelts of American mink (Neovison vison).

Fur quality and skin size are integral qualities in the mink industry and are main determinants of sales price and subsequent income for mink fur producers. Parental animals of future generations are selected based on quality grading from live animals, but selection response is obtained from dried skins sold after pelting. In this study, we evaluated traits assessed during live grading and pelt traits examined on dried skins to determine correlation between live and pelt traits. Grading traits and body weight were measured during live animal grading for 9,539 Brown American mink, and pelt quality traits and skin size were evaluated on 8,385 dried mink skins after pelting. Data were sampled from 2 yearly production cycles. Genetic parameters were estimated using the REML method implemented in the DMU package. Heritabilities and proportions of litter variance were calculated from estimated variance components for all traits, and genetic and phenotypic correlations between all traits were estimated in a series of bivariate analyses. Heritability estimates for live grading traits ranged from 0.06 to 0.28, heritability estimates for pelt quality traits ranged from 0.20 to 0.30, and finally heritability estimates for body size traits ranged from 0.43 to 0.48. Skin size and body weight were regarded as different traits for the two sexes and were therefore analysed for each sex separately. Genetic correlations between grading traits exhibited a range of 0.30-0.99 and genetic correlations between pelt quality traits ranged from 0.38 to 0.86. Genetic correlations between quality, wool density and silky appearance evaluated during live animal grading and on dried skin after pelting were 0.74, 0.41 and 0.33, respectively. Skin size and body weight were negatively correlated with pelt quality traits and ranged from -0.55 to -0.25. Using standard selection index theory and combined information from both live grading and skin evaluation increase of reliability of selection ranged from 0.6% to 14%. Due to moderate genetic correlations between traits evaluated during live grading and on dried skins, and negative correlations between pelt quality traits and body size, we concluded that traits should be selected simultaneously.

Genome-wide association analysis of milk yield traits in Nordic Red Cattle using imputed whole genome sequence variants.

BACKGROUND: The Nordic Red Cattle consisting of three different populations from Finland, Sweden and Denmark are under a joint breeding value estimation system. The long history of recording of production and health traits offers a great opportunity to study production traits and identify causal variants behind them. In this study, we used whole genome sequence level data from 4280 progeny tested Nordic Red Cattle bulls to scan the genome for loci affecting milk, fat and protein yields. RESULTS: Using a genome-wise significance threshold, regions on Bos taurus chromosomes 5, 14, 23, 25 and 26 were associated with fat yield. Regions on chromosomes 5, 14, 16, 19, 20 and 25 were associated with milk yield and chromosomes 5, 14 and 25 had regions associated with protein yield. Significantly associated variations were found in 227 genes for fat yield, 72 genes for milk yield and 30 genes for protein yield. Ingenuity Pathway Analysis was used to identify networks connecting these genes displaying significant hits. When compared to previously mapped genomic regions associated with fertility, significantly associated variations were found in 5 genes common for fat yield and fertility, thus linking these two traits via biological networks. CONCLUSION: This is the first time when whole genome sequence data is utilized to study genomic regions affecting milk production in the Nordic Red Cattle population. Sequence level data offers the possibility to study quantitative traits in detail but still cannot unambiguously reveal which of the associated variations is causative. Linkage disequilibrium creates difficulties to pinpoint the causative genes and variations. One solution to overcome these difficulties is the identification of the functional gene networks and pathways to reveal important interacting genes as candidates for the observed effects. This information on target genomic regions may be exploited to improve genomic prediction.

Increased post-operative cardiopulmonary fitness in gastric bypass patients is explained by weight loss.

Roux-en-Y gastric bypass (RYGB) leads to a major weight loss in obese patients. However, given that most patients remain obese after the weight loss, regular exercise should be part of a healthier lifestyle. The primary aim of this study was to investigate the cardiopulmonary fitness in obese patients before and after RYGB. Thirty-four patients had body composition and cardiopulmonary fitness (VO2max ) assessed and completed questionnaires regarding physical activity and function twice before RYGB (time points A and B) and 4 and 18 months after surgery (time points C and D). Weight loss was 37 ± 2 kg during the study period. VO2max increased (A: 21 ± 1 vs D: 29 mL/min/kg, P < 0.001), but absolute VO2max decreased (A: 2713 ± 126 vs 2609 ± 187 mL/min, P = 0.02) and VO2max per kilogram fat free mass did not change. Self-perceived limitations to perform exercise decreased and self-perceived physical fitness increased after RYGB. Self-reported low- and high-intensity physical activity did not change. With weight loss, self-rated fitness level increased and the limitations to perform exercise decreased in RYGB patients. Nevertheless, as shown by the lower absolute VO2max , RYGB patients do not adopt new exercise habits following surgery.

Volumetric and morphometric MRI findings in patients with mild traumatic brain injury.

OBJECTIVE: This study compared cortical and sub-cortical volumes between patients with complicated (i.e. presence of intracranial abnormality on the day-of-injury CT) and uncomplicated (i.e. absence of intracranial abnormality) mild traumatic brain injury (MTBI) 4 weeks post-injury. The study hypothesized regionally decreased brain volumes and reduced cortical thickness in patients with complicated MTBIs compared with uncomplicated MTBI. METHODS: This study was part of a larger 2 years cohort study on MTBI. Baseline clinical and magnetic resonance imaging (MRI) data were compared for those with complicated and uncomplicated MTBI. It identified 168 patients with MTBI (90 uncomplicated and 78 complicated), aged 16-65 years. 3T MRI-system (Signa HDxt, GE Medical Systems, Milwaukee, WI) and cortical reconstruction and volumetric segmentation by FreeSurfer software have been used. RESULTS: No significant differences between uncomplicated and complicated MTBIs were found in neuroanatomic volumes and cortical thickness after controlling for age, gender and education. The complicated MTBI group showed larger ventricles compared with the uncomplicated group, but this effect diluted when adjusting for potential confounders. CONCLUSION: The study findings suggest that the classification of complicated and uncomplicated MTBI may be too broad to differentiate volumetric and morphometric effects of injury in the early post-injury phase.

Short communication: Improving accuracy of predicting breeding values in Brazilian Holstein population by adding data from Nordic and French Holstein populations.

The present study investigated the improvement of prediction reliabilities for 3 production traits in Brazilian Holsteins that had no genotype information by adding information from Nordic and French Holstein bulls that had genotypes. The estimated across-country genetic correlations (ranging from 0.604 to 0.726) indicated that an important genotype by environment interaction exists between Brazilian and Nordic (or Nordic and French) populations. Prediction reliabilities for Brazilian genotyped bulls were greatly increased by including data of Nordic and French bulls, and a 2-trait single-step genomic BLUP performed much better than the corresponding pedigree-based BLUP. However, only a minor improvement in prediction reliabilities was observed in nongenotyped Brazilian cows. The results indicate that although there is a large genotype by environment interaction, inclusion of a foreign reference population can improve accuracy of genetic evaluation for the Brazilian Holstein population. However, a Brazilian reference population is necessary to obtain a more accurate genomic evaluation.

Short communication: Multi-trait estimation of genetic parameters for milk protein composition in the Danish Holstein.

Genetic parameters were estimated for the major milk proteins using bivariate and multi-trait models based on genomic relationships between animals. The analyses included, apart from total protein percentage, αS1-casein (CN), αS2-CN, ß-CN, κ-CN, α-lactalbumin, and ß-lactoglobulin, as well as the posttranslational sub-forms of glycosylated κ-CN and αS1-CN-8P (phosphorylated). Standard errors of the estimates were used to compare the models. In total, 650 Danish Holstein cows across 4 parities and days in milk ranging from 9 to 481d were selected from 21 herds. The multi-trait model generally resulted in lower standard errors of heritability estimates, suggesting that genetic parameters can be estimated with high accuracy using multi-trait analyses with genomic relationships for scarcely recorded traits. The heritability estimates from the multi-trait model ranged from low (0.05 for ß-CN) to high (0.78 for κ-CN). Genetic correlations between the milk proteins and the total milk protein percentage were generally low, suggesting the possibility to alter protein composition through selective breeding with little effect on total milk protein percentage.

Mitochondrial dysfunction and risk of cancer.

BACKGROUND: Mitochondrial mutations are commonly reported in tumours, but it is unclear whether impaired mitochondrial function per se is a cause or consequence of cancer. To elucidate this, we examined the risk of cancer in a nationwide cohort of patients with mitochondrial dysfunction. METHODS: We used nationwide results on genetic testing for mitochondrial disease and the Danish Civil Registration System, to construct a cohort of 311 patients with mitochondrial dysfunction. A total of 177 cohort members were identified from genetic testing and 134 genetically untested cohort members were matrilineal relatives to a cohort member with a genetically confirmed maternally inherited mDNA mutation. Information on cancer was obtained by linkage to the Danish Cancer Register. Standardised incidence ratios (SIRs) were used to assess the relative risk of cancer. RESULTS: During 7334 person-years of follow-up, 19 subjects developed a primary cancer. The corresponding SIR for any primary cancer was 1.06 (95% confidence interval 0.68-1.63). Subgroup analyses according to mutational subtype yielded similar results, for example, a SIR of 0.94 (95% CI 0.53 to 1.67) for the m.3243A>G maternally inherited mDNA mutation, cases=13. CONCLUSIONS: Patients with mitochondrial dysfunction do not appear to be at increased risk of cancer compared with the general population.

Single-step genomic model improved reliability and reduced the bias of genomic predictions in Danish Jersey.

A bias in the trend of genomic estimated breeding values (GEBV) was observed in the Danish Jersey population where the trend of GEBV was smaller than the deregressed proofs for individuals in the validation population. This study attempted to improve the prediction reliability and reduce the bias of predicted genetic trend in Danish Jersey. The data consisted of 1,238 Danish Jersey bulls and 611,695 cows. All bulls were genotyped with the 54K chip, and 1,744 cows were genotyped with either 7K chips (1,157 individuals) or 54K chips (587 individuals). The trait used in the analysis was protein yield. All cows with EBV were used in a single-step approach. Deregressed proofs were used as the response variable. Four alternative approaches were compared with genomic best linear unbiased prediction (GBLUP) model with bulls in the reference data (GBLUPBull): (1) GBLUP with both bulls and genotyped cows in the reference data; (2) GBLUP including a year of birth effect; (3) GEBV from a GBLUP model that accounted for the difference of EBV between dams and maternal grandsires; and (4) using a single-step approach. The results indicated all 4 alternatives could reduce the bias of predicted genetic trend and that the single-step approach performed best. However, not all these approaches improved reliability or reduced inflation of GEBV. The reliability was 0.30 and regression coefficients of deregressed proofs on GEBV were 0.69 in the scenario GBLUPBull. When genotyped cows were included in the reference population, the regression coefficients decreased to 0.59 but the reliability increased to 0.35. If a year effect was included in the model, the prediction reliability decreased to 0.29 and the regression coefficient improved to 0.75. The method in which GEBV were adjusted for the difference between dam EBV and maternal grandsire EBV led to much lower regression coefficients though the reliability increased to 0.4. The single-step approach improved both the reliability, to 0.38 and regression coefficient to 0.78. Therefore, the bias in genetic trend was reduced. The results suggest that implementing the single-step approach is an effective way to improve genomic prediction in Danish Jersey cattle.

Bootstrap study of genome-enabled prediction reliabilities using haplotype blocks across Nordic Red cattle breeds.

This study compared the accuracy of genome-enabled prediction models using individual single nucleotide polymorphisms (SNP) or haplotype blocks as covariates when using either a single breed or a combined population of Nordic Red cattle. The main objective was to compare predictions of breeding values of complex traits using a combined training population with haplotype blocks, with predictions using a single breed as training population and individual SNP as predictors. To compare the prediction reliabilities, bootstrap samples were taken from the test data set. With the bootstrapped samples of prediction reliabilities, we built and graphed confidence ellipses to allow comparisons. Finally, measures of statistical distances were used to calculate the gain in predictive ability. Our analyses are innovative in the context of assessment of predictive models, allowing a better understanding of prediction reliabilities and providing a statistical basis to effectively calibrate whether one prediction scenario is indeed more accurate than another. An ANOVA indicated that use of haplotype blocks produced significant gains mainly when Bayesian mixture models were used but not when Bayesian BLUP was fitted to the data. Furthermore, when haplotype blocks were used to train prediction models in a combined Nordic Red cattle population, we obtained up to a statistically significant 5.5% average gain in prediction accuracy, over predictions using individual SNP and training the model with a single breed.