Affect fluctuations examined with ecological momentary assessment in patients with current or remitted depression and anxiety disorders.

BACKGROUND: There is increasing interest in day-to-day affect fluctuations of patients with depressive and anxiety disorders. Few studies have compared repeated assessments of positive affect (PA) and negative affect (NA) across diagnostic groups, and fluctuation patterns were not uniformly defined. The aim of this study is to compare affect fluctuations in patients with a current episode of depressive or anxiety disorder, in remitted patients and in controls, using affect instability as a core concept but also describing other measures of variability and adjusting for possible confounders. METHODS: Ecological momentary assessment (EMA) data were obtained from 365 participants of the Netherlands Study of Depression and Anxiety with current (n = 95), remitted (n = 178) or no (n = 92) DSM-IV defined depression/anxiety disorder. For 2 weeks, five times per day, participants filled-out items on PA and NA. Affect instability was calculated as the root mean square of successive differences (RMSSD). Tests on group differences in RMSSD, within-person variance, and autocorrelation were performed, controlling for mean affect levels. RESULTS: Current depression/anxiety patients had the highest affect instability in both PA and NA, followed by remitters and then controls. Instability differences between groups remained significant when controlling for mean affect levels, but differences between current and remitted were no longer significant. CONCLUSIONS: Patients with a current disorder have higher instability of NA and PA than remitted patients and controls. Especially with regard to NA, this could be interpreted as patients with a current disorder being more sensitive to internal and external stressors and having suboptimal affect regulation.

Using phenotypic distribution models to predict livestock performance.

Livestock production systems of the developing world use indigenous breeds that locally adapted to specific agro-ecologies. Introducing commercial breeds usually results in lower productivity than expected, as a result of unfavourable genotype by environment interaction. It is difficult to predict of how these commercial breeds will perform in different conditions encountered in e.g. sub-Saharan Africa. Here, we present a novel methodology to model performance, by using growth data from different chicken breeds that were tested in Ethiopia. The suitability of these commercial breeds was tested by predicting the response of body weight as a function of the environment across Ethiopia. Phenotype distribution models were built using machine learning algorithms to make predictions of weight in the local environmental conditions based on the productivity for the breed. Based on the predicted body weight, breeds were assigned as being most suitable in a given agro-ecology or region. We identified the most important environmental variables that explained the variation in body weight across agro-ecologies for each of the breeds. Our results highlight the importance of acknowledging the role of environment in predicting productivity in scavenging chicken production systems. The use of phenotype distribution models in livestock breeding is recommended to develop breeds that will better fit in their intended production environment.

Use of geographic information system tools to predict animal breed suitability for different agro-ecological zones.

Predicting breed-specific environmental suitability has been problematic in livestock production. Native breeds have low productivity but are thought to be more robust to perform under local conditions than exotic breeds. Attempts to introduce genetically improved exotic breeds are generally unsuccessful, mainly due to the antagonistic environmental conditions. Knowledge of the environmental conditions that are shaping the breed would be needed to determine its suitability to different locations. Here, we present a methodology to predict the suitability of breeds for different agro-ecological zones using Geographic Information Systems tools and predictive habitat distribution models. This methodology was tested on the current distribution of two introduced chicken breeds in Ethiopia: the Koekoek, originally from South Africa, and the Fayoumi, originally from Egypt. Cross-validation results show this methodology to be effective in predicting breed suitability for specific environmental conditions. Furthermore, the model predicts suitable areas of the country where the breeds could be introduced. The specific climatic parameters that explained the potential distribution of each of the breeds were similar to the environment from which the breeds originated. This novel methodology finds application in livestock programs, allowing for a more informed decision when designing breeding programs and introduction programs, and increases our understanding of the role of the environment in livestock productivity.

Genotype by feed interaction for feed efficiency and growth performance traits in pigs.

A major objective of pork producers is to reduce production cost. Feeding may account for over 75% of pork production costs. Thus, selecting pigs for feed efficiency (FE) traits is a priority in pig breeding programs. While in the Americas, pigs are typically fed high-input diets, based on corn and soybean meal (CS); in Western Europe, pigs are commonly fed diets based on wheat and barley with high amounts of added protein-rich coproducts (WB), e.g., from milling and seed-oil industries. These two feeding scenarios provided a realistic setting for investigating a specific type of genotype by environment interaction; thus, we investigated the genotype by feed interaction (GxF). In the presence of a GxF, different feed compositions should be considered when selecting for FE. This study aimed to 1) verify the presence of a GxF for FE and growth performance traits in different growth phases (starter, grower, and finisher) of 3-way crossbred growing-finishing pigs fed either a CS (547 boars and 558 gilts) or WB (567 boars and 558 gilts) diet; and 2) to assess and compare the expected responses to direct selection under the 2 diets and the expected correlated responses for one diet to indirect selection under the other diet. We found that GxF did not interfere in the ranking of genotypes under both diets for growth, protein deposition, feed intake, energy intake, or feed conversion rate. Therefore, for these traits, we recommend changing the diet of growing-finishing pigs from high-input feed (i.e., CS) to feed with less valuable ingredients, as WB, to reduce production costs and the environmental impact, regardless of which diet is used in selection. We found that GxF interfered in the ranking of genotypes and caused heterogeneity of genetic variance under both diets for lipid deposition (LD), residual energy intake (REI), and residual feed intake (RFI). Thus, selecting pigs under a diet different from the diet used for growing-finishing performance could compromise the LD in all growth phases, compromise the REI and RFI during the starter phase, and severely compromise the REI during the grower phase. In particular, when pigs are required to consume a WB diet for growing-finishing performance, pigs should be selected for FE under the same diet. Breeding pigs for FE under lower-input diets should be considered, because FE traits will become more important and lower-input diets will become more widespread in the near future.

Effects of incorporating environmental cost and risk aversion on economic values of pig breeding goal traits.

Economic values (EVs) of traits, accounting for environmental impacts and risk preferences of farmers, are required to design breeding goals that contribute to both economic and environmental sustainability. The objective of this study was to assess the effects of incorporating environmental costs and the risk preferences of farmers on the EVs of pig breeding goal traits. A breeding goal consisting of both sow efficiency and production traits was defined for a typical Brazilian farrow-to-finish pig farm with 1,500 productive sows. A mean-variance utility function was employed for deriving the EVs at finishing pig level assuming fixed slaughter weight. The inclusion of risk and risk aversion reduces the economic weights of sow efficiency traits (17%) while increasing the importance of production traits (7%). For a risk-neutral producer, inclusion of environmental cost reduces the economic importance of sow efficiency traits (3%) while increasing the importance of production traits (1%). Genetic changes of breeding goal traits by their genetic standard deviations reduce emissions of greenhouse gases, and excretions of nitrogen and phosphorus per finished pig by up to 6% while increasing farm profit. The estimated EVs could be used to improve selection criteria and thereby contribute to the sustainability of pig production systems.

Genetic correlations between feed efficiency traits, and growth performance and carcass traits in purebred and crossbred pigs.

Selection for feed efficiency (FE) is a strategy to reduce the production costs per unit of animal product, which is one of the major objectives of current animal breeding programs. In pig breeding, selection for FE and other traits traditionally takes place based on purebred pig (PB) performance at the nucleus level, while pork production typically makes use of crossbred animals (CB). The success of this selection, therefore, depends on the genetic correlation between the performance of PB and CB (rpc) and on the genetic correlation (rg) between FE and the other traits that are currently under selection. Different traits are being used to account for FE, but the rpc has been reported only for feed conversion rate. Therefore, this study aimed 1) to estimate the rpc for growth performance, carcass, and FE traits; 2) to estimate rg between traits within PB and CB populations; and 3) to compare three different traits representing FE: feed conversion rate, residual energy intake (REI), and residual feed intake (RFI). Phenotypes of 194,445 PB animals from 23 nucleus farms, and 46,328 CB animals from three farms where research is conducted under near commercial production conditions were available for this study. From these, 22,984 PB and 8,657 CB presented records for feed intake. The PB population consisted of five sire and four dam lines, and the CB population consisted of terminal cross-progeny generated by crossing sires from one of the five PB sire lines with commercially available two-way maternal sow crosses. Estimates of rpc ranged from 0.61 to 0.71 for growth performance traits, from 0.75 to 0.82 for carcass traits, and from 0.62 to 0.67 for FE traits. Estimates of rg between growth performance, carcass, and FE traits differed within PB and CB. REI and RFI showed substantial positive rg estimates in PB (0.84) and CB (0.90) populations. The magnitudes of rpc estimates indicate that genetic progress is being realized in CB at the production level from selection on PB performance at nucleus level. However, including CB phenotypes recorded on production farms, when predicting breeding values, has the potential to increase genetic progress for these traits in CB. Given the genetic correlations with growth performance traits and the genetic correlation between the performance of PB and CB, REI is an attractive FE parameter for a breeding program.

A stochastic bio-economic pig farm model to assess the impact of innovations on farm performance.

Recently developed innovations may improve the economic and environmental sustainability of pig production systems. Generic models are needed to assess the impact of innovations on farm performance. Here we developed a stochastic bio-economic farm model for a typical farrow-to-finish pig farm to assess the impact of innovations on private and social profits. The model accounts for emissions of greenhouse gases from feed production and manure by using the shadow price of CO2, and for stochasticity of economic and biological parameters. The model was applied to assess the impact of using locally produced alternative feed sources (i.e. co-products) in the diets of finishing pigs on private and social profits of a typical Brazilian farrow-to-finish pig farm. Three cases were defined: a reference case (with a standard corn-soybean meal-based finishing diet), a macaúba case (with a macaúba kernel cake-based finishing diet) and a co-products case (with a co-products-based finishing diet). Pigs were assumed to be fed to equal net energy intakes in the three cases. Social profits are 34% to 38% lower than private profits in the three cases. Private and social profits are about 11% and 14% higher for the macaúba case than the reference case, whereas they are 3% and 7% lower for the co-products case, respectively. Environmental costs are higher under the alternative cases than the reference case suggesting that other benefits (e.g. costs and land use) should be considered to utilize co-products. The CV of farm profits is between 75% and 87% in the three cases following from the volatility of prices over time and variations in biological parameters between fattening pigs.

Genetic parameters for semen quality and quantity traits in five pig lines.

We aimed to estimate genetic parameters for semen quality and quantity traits as well as for within-boar variation of these traits to evaluate their inclusion in breeding goals. Genetic parameters were estimated within line using a multiple-trait (4 × 4) repeatability animal model fitted for 5 pig lines, considering 4 semen traits: sperm motility (MOT), sperm progressive motility (PROMOT), log-transformed number of sperm cells per ejaculate (lnN), and total morphological abnormalities (ABN). The within-boar variation of these traits was analyzed based on a multiple-trait (2 × 2) approach for SD and average (AVG) and a single-trait analysis for CV. The average heritabilities across the 5 lines estimated by multiple-trait analysis were 0.18 ± 0.07 (MOT), 0.22 ± 0.08 (PROMOT), 0.16 ± 0.04 (lnN), and 0.20 ± 0.04 (ABN). The average genetic correlations were favorable between MOT and PROMOT (0.86 ± 0.10), between MOT and ABN (-0.66 ± 0.25), and between PROMOT and ABN (-0.65 ± 0.25). As determined by within-boar variation analysis, AVG exhibited the greatest heritabilities followed by SD and CV, respectively, for the traits MOT and ABN. For PROMOT, average SD heritability was lower than CV heritability, whereas for lnN, they were the same. The average genetic correlations between AVG and SD were favorable for MOT (-0.60 ± 0.13), PROMOT (-0.79 ± 0.14), and ABN (0.78 ± 0.17). The moderate heritabilities indicate the possibility of effective selection of boars based on semen traits. Average and SD are proposed as appropriate traits for selection regarding uniformity.

Using markers with large effect in genetic and genomic predictions.

The first attempts of applying marker-assisted selection (MAS) in animal breeding were not very successful because the identification of markers closely linked to QTL using low-density microsatellite panels was difficult. More recently, the use of high-density SNP panels in genome-wide association studies (GWAS) have increased the power and precision of identifying markers linked to QTL, which offer new possibilities for MAS. However, when GWAS started to be performed, the focus of many breeders had already shifted from the use of MAS to the application of genomic selection (using all available markers without any preselection of markers linked to QTL). In this study, we aimed to evaluate the prediction accuracy of a MAS approach that accounts for GWAS findings in the prediction models by including the most significant SNP from GWAS as a fixed effect in the marker-assisted BLUP (MA-BLUP) and marker-assisted genomic BLUP (MA-GBLUP) prediction models. A second aim was to compare the prediction accuracies from the marker-assisted models with those obtained from a Bayesian variable selection (BVS) model. To compare the prediction accuracies of traditional BLUP, MA-BLUP, genomic BLUP (GBLUP), MA-GBLUP, and BVS, we applied these models to the trait "number of teats" in 4 distinct pig populations, for validation of the results. The most significant SNP in each population was located at approximately 103.50 Mb on chromosome 7. Applying MAS by accounting for the most significant SNP in the prediction models resulted in improved prediction accuracy for number of teats in all evaluated populations compared with BLUP and GBLUP. Using MA-BLUP instead of BLUP, the increase in prediction accuracy ranged from 0.021 to 0.124, whereas using MA-GBLUP instead of GBLUP, the increase in prediction accuracy ranged from 0.003 to 0.043. The BVS model resulted in similar or higher prediction accuracies than MA-GBLUP. For the trait number of teats, BLUP resulted in the lowest prediction accuracies whereas the highest were observed when applying MA-GBLUP or BVS. In the same data set, MA-BLUP can yield similar or superior accuracies compared with GBLUP. The superiority of MA-GBLUP over traditional GBLUP is more pronounced when training populations are smaller and when relationships between training and validation populations are smaller. Marker-assisted GBLUP did not outperform BVS but does have implementation advantages in large-scale evaluations.

ATP and NADPH coated iron oxide nanoparticles for targeting of highly metabolic tumor cells.

The metabolic activity of tumor cells is known to be higher as compared to that of normal cells, which has been previously exploited to deliver nanomedicines to highly metabolic tumor cells. Unfortunately, current strategies, which are mostly based on complex energy sources, such as sugars, showed insufficient accumulation at the target sites. We here report the coating of IONPs with two essential units of cellular metabolism: adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide phosphate (NADPH). ATP and NADPH were directly bound to the IONPs' surface using a simple aqueous method. Both molecules were used as coatings, i.e. as stabilizing agents, but also simultaneously as targeting molecules to deliver IONPs to highly metabolic tumor cells. Indeed, we found that the uptake of ATP-IONPs and NADPH-IONPs is correlated with the metabolic activity of tumor cells, especially regarding their cellular ATP levels and NADPH consumption. We also measured one of the highest MRI r2 relaxivities for both ATP-IONPs and NADPH-IONPs. With the direct coating of IONPs with ATP and NADPH, we therefore provide an optimal platform to stabilize IONPs and at the same time promising properties for the targeting and detection of highly metabolic tumor cells.

Citation bias and selective focus on positive findings in the literature on the serotonin transporter gene (5-HTTLPR), life stress and depression.

BACKGROUND: Caspi et al.'s 2003 report that 5-HTTLPR genotype moderates the influence of life stress on depression has been highly influential but remains contentious. We examined whether the evidence base for the 5-HTTLPR-stress interaction has been distorted by citation bias and a selective focus on positive findings. METHOD: A total of 73 primary studies were coded for study outcomes and focus on positive findings in the abstract. Citation rates were compared between studies with positive and negative results, both within this network of primary studies and in Web of Science. In addition, the impact of focus on citation rates was examined. RESULTS: In all, 24 (33%) studies were coded as positive, but these received 48% of within-network and 68% of Web of Science citations. The 38 (52%) negative studies received 42 and 23% of citations, respectively, while the 11 (15%) unclear studies received 10 and 9%. Of the negative studies, the 16 studies without a positive focus (42%) received 47% of within-network citations and 32% of Web of Science citations, while the 13 (34%) studies with a positive focus received 39 and 51%, respectively, and the nine (24%) studies with a partially positive focus received 14 and 17%. CONCLUSIONS: Negative studies received fewer citations than positive studies. Furthermore, over half of the negative studies had a (partially) positive focus, and Web of Science citation rates were higher for these studies. Thus, discussion of the 5-HTTLPR-stress interaction is more positive than warranted. This study exemplifies how evidence-base-distorting mechanisms undermine the authenticity of research findings.

Impact of fitting dominance and additive effects on accuracy of genomic prediction of breeding values in layers.

Most genomic prediction studies fit only additive effects in models to estimate genomic breeding values (GEBV). However, if dominance genetic effects are an important source of variation for complex traits, accounting for them may improve the accuracy of GEBV. We investigated the effect of fitting dominance and additive effects on the accuracy of GEBV for eight egg production and quality traits in a purebred line of brown layers using pedigree or genomic information (42K single-nucleotide polymorphism (SNP) panel). Phenotypes were corrected for the effect of hatch date. Additive and dominance genetic variances were estimated using genomic-based [genomic best linear unbiased prediction (GBLUP)-REML and BayesC] and pedigree-based (PBLUP-REML) methods. Breeding values were predicted using a model that included both additive and dominance effects and a model that included only additive effects. The reference population consisted of approximately 1800 animals hatched between 2004 and 2009, while approximately 300 young animals hatched in 2010 were used for validation. Accuracy of prediction was computed as the correlation between phenotypes and estimated breeding values of the validation animals divided by the square root of the estimate of heritability in the whole population. The proportion of dominance variance to total phenotypic variance ranged from 0.03 to 0.22 with PBLUP-REML across traits, from 0 to 0.03 with GBLUP-REML and from 0.01 to 0.05 with BayesC. Accuracies of GEBV ranged from 0.28 to 0.60 across traits. Inclusion of dominance effects did not improve the accuracy of GEBV, and differences in their accuracies between genomic-based methods were small (0.01-0.05), with GBLUP-REML yielding higher prediction accuracies than BayesC for egg production, egg colour and yolk weight, while BayesC yielded higher accuracies than GBLUP-REML for the other traits. In conclusion, fitting dominance effects did not impact accuracy of genomic prediction of breeding values in this population.

Accounting for genetic architecture in single- and multipopulation genomic prediction using weights from genomewide association studies in pigs.

We studied the effect of including GWAS results on the accuracy of single- and multipopulation genomic predictions. Phenotypes (backfat thickness) and genotypes of animals from two sire lines (SL1, n = 1146 and SL3, n = 1264) were used in the analyses. First, GWAS were conducted for each line and for a combined data set (both lines together) to estimate the genetic variance explained by each SNP. These estimates were used to build matrices of weights (D), which was incorporated into a GBLUP method. Single population evaluated with traditional GBLUP had accuracies of 0.30 for SL1 and 0.31 for SL3. When weights were employed in GBLUP, the accuracies for both lines increased (0.32 for SL1 and 0.34 for SL3). When a multipopulation reference set was used in GBLUP, the accuracies were higher (0.36 for SL1 and 0.32 for SL3) than in single-population prediction. In addition, putting together the multipopulation reference set and the weights from the combined GWAS provided even higher accuracies (0.37 for SL1, and 0.34 for SL3). The use of multipopulation predictions and weights estimated from a combined GWAS increased the accuracy of genomic predictions.

Accuracy of genomic prediction of purebreds for cross bred performance in pigs.

In pig breeding, as the final product is a cross bred (CB) animal, the goal is to increase the CB performance. This goal requires different strategies for the implementation of genomic selection from what is currently implemented in, for example dairy cattle breeding. A good strategy is to estimate marker effects on the basis of CB performance and subsequently use them to select pure bred (PB) breeding animals. The objective of our study was to assess empirically the predictive ability (accuracy) of direct genomic values of PB for CB performance across two traits using CB and PB genomic and phenotypic data. We studied three scenarios in which genetic merit was predicted within each population, and four scenarios where PB genetic merit for CB performance was predicted based on either CB or a PB training data. Accuracy of prediction of PB genetic merit for CB performance based on CB training data ranged from 0.23 to 0.27 for gestation length (GLE), whereas it ranged from 0.11 to 0.22 for total number of piglets born (TNB). When based on PB training data, it ranged from 0.35 to 0.55 for GLE and from 0.30 to 0.40 for TNB. Our results showed that it is possible to predict PB genetic merit for CB performance using CB training data, but predictive ability was lower than training using PB training data. This result is mainly due to the structure of our data, which had small-to-moderate size of the CB training data set, low relationship between the CB training and the PB validation populations, and a high genetic correlation (0.94 for GLE and 0.90 for TNB) between the studied traits in PB and CB individuals, thus favouring selection on the basis of PB data.

Accuracy of genomic prediction using imputed whole-genome sequence data in white layers.

There is an increasing interest in using whole-genome sequence data in genomic selection breeding programmes. Prediction of breeding values is expected to be more accurate when whole-genome sequence is used, because the causal mutations are assumed to be in the data. We performed genomic prediction for the number of eggs in white layers using imputed whole-genome resequence data including ~4.6 million SNPs. The prediction accuracies based on sequence data were compared with the accuracies from the 60 K SNP panel. Predictions were based on genomic best linear unbiased prediction (GBLUP) as well as a Bayesian variable selection model (BayesC). Moreover, the prediction accuracy from using different types of variants (synonymous, non-synonymous and non-coding SNPs) was evaluated. Genomic prediction using the 60 K SNP panel resulted in a prediction accuracy of 0.74 when GBLUP was applied. With sequence data, there was a small increase (~1%) in prediction accuracy over the 60 K genotypes. With both 60 K SNP panel and sequence data, GBLUP slightly outperformed BayesC in predicting the breeding values. Selection of SNPs more likely to affect the phenotype (i.e. non-synonymous SNPs) did not improve the accuracy of genomic prediction. The fact that sequence data were based on imputation from a small number of sequenced animals may have limited the potential to improve the prediction accuracy. A small reference population (n = 1004) and possible exclusion of many causal SNPs during quality control can be other possible reasons for limited benefit of sequence data. We expect, however, that the limited improvement is because the 60 K SNP panel was already sufficiently dense to accurately determine the relationships between animals in our data.

Genomic prediction of growth in pigs based on a model including additive and dominance effects.

Independent of whether prediction is based on pedigree or genomic information, the focus of animal breeders has been on additive genetic effects or 'breeding values'. However, when predicting phenotypes rather than breeding values of an animal, models that account for both additive and dominance effects might be more accurate. Our aim with this study was to compare the accuracy of predicting phenotypes using a model that accounts for only additive effects (MA) and a model that accounts for both additive and dominance effects simultaneously (MAD). Lifetime daily gain (DG) was evaluated in three pig populations (1424 Pietrain, 2023 Landrace, and 2157 Large White). Animals were genotyped using the Illumina SNP60K Beadchip and assigned to either a training data set to estimate the genetic parameters and SNP effects, or to a validation data set to assess the prediction accuracy. Models MA and MAD applied random regression on SNP genotypes and were implemented in the program Bayz. The additive heritability of DG across the three populations and the two models was very similar at approximately 0.26. The proportion of phenotypic variance explained by dominance effects ranged from 0.04 (Large White) to 0.11 (Pietrain), indicating that importance of dominance might be breed-specific. Prediction accuracies were higher when predicting phenotypes using total genetic values (sum of breeding values and dominance deviations) from the MAD model compared to using breeding values from both MA and MAD models. The highest increase in accuracy (from 0.195 to 0.222) was observed in the Pietrain, and the lowest in Large White (from 0.354 to 0.359). Predicting phenotypes using total genetic values instead of breeding values in purebred data improved prediction accuracy and reduced the bias of genomic predictions. Additional benefit of the method is expected when applied to predict crossbred phenotypes, where dominance levels are expected to be higher.

Genome-wide association study reveals regions associated with gestation length in two pig populations.

Reproduction traits, such as gestation length (GLE), play an important role in dam line breeding in pigs. The objective of our study was to identify single nucleotide polymorphisms (SNPs) that are associated with GLE in two pig populations. Genotypes and deregressed breeding values were available for 2081 Dutch Landrace-based (DL) and 2301 Large White-based (LW) pigs. We identified two QTL regions for GLE, one in each population. For DL, three associated SNPs were detected in one QTL region spanning 0.52 Mbp on Sus scrofa chromosome (SSC) 2. For LW, four associated SNPs were detected in one region of 0.14 Mbp on SSC5. The region on SSC2 contains the heparin-binding EGF-like growth factor (HBEGF) gene, which promotes embryo implantation and has been described to be involved in embryo survival throughout gestation. The associated SNP can be used for marker-assisted selection in the studied populations, and further studies of the HBEGF gene are warranted to investigate its role in GLE.