Genome-Wide Association Study and Gene Expression Analysis Identifies CD84 as a Predictor of Response to Etanercept Therapy in Rheumatoid Arthritis

Anti-tumor necrosis factor alpha (anti-TNF) biologic therapy is a widely used treatment for rheumatoid arthritis (RA). It is unknown why some RA patients fail to respond adequately to anti-TNF therapy, which limits the development of clinical biomarkers to predict response or new drugs to target refractory cases. To understand the biological basis of response to anti-TNF therapy, we conducted a genome-wide association study (GWAS) meta-analysis of more than 2 million common variants in 2,706 RA patients from 13 different collections. Patients were treated with one of three anti-TNF medications: etanercept (n = 733), infliximab (n = 894), or adalimumab (n = 1,071). We identified a SNP (rs6427528) at the 1q23 locus that was associated with change in disease activity score (ΔDAS) in the etanercept subset of patients (P = 8×10-8), but not in the infliximab or adalimumab subsets (P>0.05). The SNP is predicted to disrupt transcription factor binding site motifs in the 3′ UTR of an immune-related gene, CD84, and the allele associated with better response to etanercept was associated with higher CD84 gene expression in peripheral blood mononuclear cells (P = 1×10-11 in 228 non-RA patients and P = 0.004 in 132 RA patients). Consistent with the genetic findings, higher CD84 gene expression correlated with lower cross-sectional DAS (P = 0.02, n = 210) and showed a non-significant trend for better ΔDAS in a subset of RA patients with gene expression data (n = 31, etanercept-treated). A small, multi-ethnic replication showed a non-significant trend towards an association among etanercept-treated RA patients of Portuguese ancestry (n = 139, P = 0.4), but no association among patients of Japanese ancestry (n = 151, P = 0.8). Our study demonstrates that an allele associated with response to etanercept therapy is also associated with CD84 gene expression, and further that CD84 expression correlates with disease activity. These findings support a model in which CD84 genotypes and/or expression may serve as a useful biomarker for response to etanercept treatment in RA patients of European ancestry. © 2013 Cui et al

Functional treatment versus plaster for simple elbow dislocations (FuncSiE): a randomized trial

Background. Elbow dislocations can be classified as simple or complex. Simple dislocations are characterized by the absence of fractures, while complex dislocations are associated with fractures. After reduction of a simple dislocation, treatment options include immobilization in a static plaster for different periods of time or so-called functional treatment. Functional treatment is characterized by early active motion within the limits of pain with or without the use of a sling or hinged brace. Theoretically, functional treatment should prevent stiffness without introducing increased joint instability. The primary aim of this randomized controlled trial is to compare early functional treatment versus plaster immobilization following simple dislocations of the elbow. Methods/Design. The design of the study will be a multicenter randomized controlled trial of 100 patients who have sustained a simple elbow dislocation. After reduction of the dislocation, patients are randomized between a pressure bandage for 5-7 days and early functional treatment or a plaster in 90 degrees flexion, neutral position for pro-supination for a period of three weeks. In the functional group, treatment is started with early active motion within the limits of pain. Function, pain, and radiographic recovery will be evaluated at regular intervals over the subsequent 12 months. The primary outcome measure is the Quick Disabilities of the Arm, Shoulder, and Hand score. The secondary outcome measures are the Mayo Elbow Performance Index, Oxford elbow score, pain level at both sides, range of motion of the elbow joint at both sides, rate of secondary interventions and complication rates in both groups (secondary dislocation, instability, relaxation), health-related quality of life (Short-Form 36 and EuroQol-5D), radiographic appearance of the elbow joint (degenerative changes and heterotopic ossifications), costs, and cost-effectiveness. Discussion. The successful completion of this trial will provide evidence on the effectiveness of a functional treatment for the management of simple elbow dislocations. Trial Registration. The trial is registered at the Netherlands Trial Register (NTR2025)

Relative contribution of production chain phases to health and performance of broiler chickens : a field study

There is increasing evidence that health and performance of the breeder flock significantly contributes to health and performance of their progeny. Data of broiler performance and health are routinely collected in various stages of the broiler production chain. In the Netherlands, the broiler chain operates at a relatively non-integrated level and the various databases are usually not connected. Connecting databases may however provide important information to improve chain performance. The aim of the present study was to determine systematic effects of broiler breeder production farm or flock on health (mortality and antibiotics use) and performance of their offspring, using data routinely collected at the different stages of the production chain. Broiler flock data collected over 6 yr (daily growth, slaughter weight, carcass weight uniformity, carcass condemnations, first week and total mortality, and antibiotics use) were linked to breeder flocks and farms. In total, 2,174 broiler flock records (at house level) of 74 broiler farms were linked to 88 broiler breeder farms and 209 breeder flocks. A mixed model analysis was applied to simultaneously estimate effects of season, parent flock age, time trend, and the contribution of the different chain phases to broiler performance and health. No systematic effects of breeder farm and only small systematic effects of breeder flock on broiler health and performance were found. The largest breeder flock effect was found for carcass condemnations (estimated contribution to the variance component: 7%). Most variation on broiler health and performance was explained by broiler farm and “day-old chick batch.” The latter refers to the rest variance that could not be explained by other factors, i.e., incidental effects linked to the specific day-old chick batch and the stage between the breeder and broiler farm. Our results suggest that systematic effects of breeder flock and farm could have been overruled by (management in) the hatchery phase and the broiler farm. This indicates room for improvement of management in these production phases.</p

Fast- and slower-growing broilers respond similarly to a reduction in stocking density with regard to gait, hock burn, skin lesions, cleanliness, and performance

ABSTRACT: There is an increasing trend toward broiler production systems with higher welfare requirements. Breed and stocking density are considered key factors for broiler welfare that are often specified as criteria for such higher welfare systems. However, it remains unknown how slower-growing broilers respond to a reduction in stocking density with regard to their welfare and performance, and whether this response differs from fast-growing broilers. Therefore, we compared fast- (F) and slower-growing broilers (S) housed at 4 different stocking densities (24, 30, 36, and 42 kg/m2, based on slaughter weight) and measured their welfare scores (i.e., gait, footpad dermatitis, hock burn, skin lesions and cleanliness), litter quality and performance. The experiment had a 2 × 4 factorial design with 4 replicates (pens) per treatment (32 pens in total). Thinning (15%) was done in a 50/50 male/female ratio at 38 (F) and 44 (S) d of age (estimated body weight of 2.2 kg). We hypothesized that breeds would respond differently to a reduction in stocking density. Contrary to our hypothesis, only one interaction between breed and stocking density was found on footpad dermatitis, indicating that fast- and slower-growing broilers generally showed similar responses to a reduction in stocking density. F broilers showed a steeper decline in the prevalence of footpad dermatitis with reducing stocking density compared to S broilers. Broilers housed at lower stocking densities (24 and/or 30 kg/m2) showed improved welfare measures, litter quality and performance compared to those housed at higher stocking densities (36 and/or 42 kg/m2). S broilers had better welfare scores (gait, footpad dermatitis and skin lesions), litter quality and lower performance compared to F broilers. In conclusion, reducing stocking density improved welfare of both F and S broilers, but more for F broilers in case of footpad dermatitis, and using S broilers improved welfare compared to F broilers. Reducing stocking density and using slower-growing broilers benefits broiler welfare, where combining both would further improve broiler welfare

Diet dilution and feeding frequency have only minor effects on the behaviour of broiler breeder pullets

During the rearing period, broiler breeders are feed restricted to prevent the negative impact of fast growth and high body weight on health and reproduction. Feed restriction causes frustration and stress, resulting in stereotypic pecking and hyperactivity. Nutritional strategies have the potential to reduce these welfare issues. Using a 2 × 2 factorial completely randomized block design, pullets were fed with two diet densities and two feeding frequencies during rearing. From 3–23 weeks of age (WOA), pullets received either a standard control diet (CON) or a 16% diluted diet (DIL) containing oat hulls. These diets were provided either once (FO) or twice (FT) a day. After 23 WOA, all pullets received the same standard layer diet once a day. Home pen behaviour was observed by scan sampling at 5, 10, 15, 20, 30 and 39 WOA over eight observation sessions. Furthermore, pullets were subjected to Novel Food Tests (12 and 17 WOA) and Novel Object Tests (5, 10, 15 and 20 WOA). Minor treatment effects were found for foraging and sitting behaviour that varied with age during rearing. Feeding frequency influenced the behavioural patterns of all home pen behaviours (P < 0.001; object pecking P = 0.034), while diet dilution only affected the expression of foraging behaviour during the day (P = 0.007). In all treatment groups, many pullets were observed standing and walking in anticipation of the first meal. After the first meal and before the second meal, more FT pullets were observed standing and walking, while during and after the second meal more FO pullets were observed sitting and performing comfort behaviour. Feeding twice a day resulted in lower daily peaks in drinking behaviour. In the laying period, when all birds received the same layer diet at the same frequency, those who were fed twice daily during rearing foraged more than those who were fed once (P = 0.028) and birds that received a diluted diet during rearing tended to drink more than birds that received the control diet (P = 0.083). Few treatment effects were found in the Novel Food and Novel Object Tests, indicating that diet dilution and/or feeding frequency, as applied here, did not affect fearful behaviour or the motivation to explore. In conclusion, this study showed that neither diet dilution, twice-daily feeding, or the combination of these, improved broiler breeder welfare during rearing and laying. Some changes in the pattern of home pen behaviour were found that indicated a response to the frequency of food provisioning

Effects of on-farm and traditional hatching on welfare, health, and performance of broiler chickens

In on-farm hatching systems, eggs that have been incubated for 18 D are transported to the broiler farm. After hatching around day 21, the chicks have immediate access to feed and water. By contrast, traditionally hatched chicks are in early life exposed to dust and pathogens in the hatcher, handling procedures, and transport and remain without feed and water until they have arrived on the farm 1 to 3 D after hatching. We compared welfare and performance of on-farm hatched (OH) and traditionally hatched control (C) Ross 308 broiler chickens from day 0 to 40, housed under semicommercial conditions. The experiment included 3 production cycles in 4 rooms, with each room containing 1 OH and 1 C pen with 1,150 chickens in each pen. Per cycle, C and OH chicks were from the same batch of eggs of 1 parent stock flock. Day-old chick quality was worse for OH than C chickens (hock and navel score; P < 0.05). On-farm hatched chickens were heavier than C chickens until day 21 of age (P < 0.05). Total mortality was significantly lower in OH compared with C pens (P < 0.05). A tendency for lower footpad dermatitis scores was found in OH pens compared with C pens (P < 0.10), probably because of the dryer litter in OH than C pens (P < 0.05). No differences between treatments were found in gait, hock burn, cleanliness, and injury scores, and no or only minor, short lasting differences were found in pathology and intestinal histology. In conclusion, the present study showed that on-farm hatching may be beneficial for broiler welfare, as it reduced total mortality and resulted in dryer litter which is known to be beneficial for reducing footpad dermatitis.</p

Comparative assessment of general behaviour and fear-related responses in hatchery-hatched and on-farm hatched broiler chickens

Traditionally, broiler chickens hatch in the hatchery and they are usually not provided with feed and water until placement at the farm. This can have negative effects on their health and welfare. Therefore, alternative systems providing early nutrition, for instance by hatching eggs in a poultry house (on-farm hatching) are increasingly being used in practice. However, information on the behaviour and welfare of on-farm hatched chickens in relation to hatchery-hatched chickens is very limited. This study aims to gain basic knowledge of the behaviour of on-farm hatched chickens (OH) by comparing them to a control group (C) hatched in the hatchery. In addition, fear-related responses were assessed as indicators of chicken welfare. About 13,800 chickens per treatment group were reared in three consecutive batches in eight floor pens under semi-commercial conditions. Direct behavioural observations and three different fear tests, i.e. a novel environment, a human approach and a novel object test, were carried out between two and 36 days of age. Except for ‘disturbance behaviour’ (i.e. pushing or overrunning another chicken), which was more often performed by the OH chickens (F1,3 = 35.10, P < 0.05), no effect of treatment was found on general behaviour. In contrast, nearly all observed behaviours were affected by the chickens’ age (F4,24 = 4.02–41.81, P < 0.05). In the fear tests, most variables, for instance average latency of chickens touching a human and the number of chickens in the vicinity of a novel object, differed between the treatments (P < 0.05) with OH chickens being more fearful and less active. The present results indicate that the hatching system (hatchery-hatching vs. on-farm hatching) seems to have limited effects on broiler chicken activity and general behaviours. In test situations, however, hatchery-hatched chickens showed more active and less fearful responses compared to on-farm hatched chickens. The underlying causes for these differences in response to more challenging situations remain to be investigated further, as these may be related to a higher intrinsic motivation to search for food or more exposure to humans or objects in the hatchery in C chickens as compared to OH chickens, but also to differences in coping style or development of cognitive abilities between the treatment groups

Comparative assessment of general behaviour and fear-related responses in hatchery-hatched and on-farm hatched broiler chickens

Traditionally, broiler chickens hatch in the hatchery and they are usually not provided with feed and water until placement at the farm. This can have negative effects on their health and welfare. Therefore, alternative systems providing early nutrition, for instance by hatching eggs in a poultry house (on-farm hatching) are increasingly being used in practice. However, information on the behaviour and welfare of on-farm hatched chickens in relation to hatchery-hatched chickens is very limited. This study aims to gain basic knowledge of the behaviour of on-farm hatched chickens (OH) by comparing them to a control group (C) hatched in the hatchery. In addition, fear-related responses were assessed as indicators of chicken welfare. About 13,800 chickens per treatment group were reared in three consecutive batches in eight floor pens under semi-commercial conditions. Direct behavioural observations and three different fear tests, i.e. a novel environment, a human approach and a novel object test, were carried out between two and 36 days of age. Except for ‘disturbance behaviour’ (i.e. pushing or overrunning another chicken), which was more often performed by the OH chickens (F1,3 = 35.10, P < 0.05), no effect of treatment was found on general behaviour. In contrast, nearly all observed behaviours were affected by the chickens’ age (F4,24 = 4.02–41.81, P < 0.05). In the fear tests, most variables, for instance average latency of chickens touching a human and the number of chickens in the vicinity of a novel object, differed between the treatments (P < 0.05) with OH chickens being more fearful and less active. The present results indicate that the hatching system (hatchery-hatching vs. on-farm hatching) seems to have limited effects on broiler chicken activity and general behaviours. In test situations, however, hatchery-hatched chickens showed more active and less fearful responses compared to on-farm hatched chickens. The underlying causes for these differences in response to more challenging situations remain to be investigated further, as these may be related to a higher intrinsic motivation to search for food or more exposure to humans or objects in the hatchery in C chickens as compared to OH chickens, but also to differences in coping style or development of cognitive abilities between the treatment groups

Effect of early life hypoxia and diet composition on growth, feed intake and oxygen consumption of rainbow trout (Oncorhynchus mykiss) in later life

Session Nutrition: Physiology and RequirementsEffect of early life hypoxia and diet composition on growth, feed intake and oxygen consumption of rainbow trout (Oncorhynchus mykiss) in later life. Aquaculture Europe 201