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Background The modality by which haemodialysis (HD) is delivered [arteriovenous fistula (AVF), arteriovenous graft (AVG) or central venous catheter (CVC)] varies widely and is influenced by clinical evidence, patient factors and the prevailing service configuration. The aim of this study was to determine the outcome and impact of access strategy on patient outcome by mapping out the HD journey in a cohort of incident patients. Methods A 2-year cohort of consecutive incident HD patients from the point of referral for first dialysis access to completion of the first 365 days of HD was prospectively reviewed. Data were sought on access type; radiological, surgical and other access-related activity; bacteraemic events; admission rates and cumulative financial cost. Results A total of 144 patients started RRT for the first time with HD over the 2-year period. All were followed up to 1 year after starting HD, generating a total of 47 753 observed HD days. Activity prior to starting HD for the full cohort was found to average 0.92 arteriovenous (AV) access creation procedures, 0.40 CVC insertions, 0.14 interventional radiology procedures and 0.41 ultrasound examinations per patient. The small number of patients who started on an AVG had a tendency towards higher pre-HD surgical and imaging activity than those who started on an AVF or CVC. Activity after starting HD varied greatly with the access type used at the start of HD, with AVF patients experiencing less hospitalization, procedure and imaging activity and financial costs compared with those who start HD with a CVC. Patients who started on an AVG had a tendency towards lower surgical activity rates and financial costs than those who started on a CVC. Conclusions Providing, maintaining and dealing with the complications of HD vascular access places a significant burden of activity that is shared across nephrology, surgery and imaging services. A well-functioning AVF is associated with the lowest burden, whereas a failed AVF or CVC access is associated with the highest burden. Patient journeys are shaped by the vascular access that they use and we suggest that the contemporary pursuit of HD access should focus on delivering personalized access solutions.

Summary Environmental descriptors derived from mean performances of contemporary groups (CGs) are assumed to capture any known and unknown environmental challenges. The objective of this paper was to obtain a finer definition of the unknown challenges, by adjusting CG estimates for the known climatic effects of monthly maximum air temperature (MaxT), minimum air temperature (MinT) and monthly rainfall (Rain). As the unknown component could include infection challenges, these refined descriptors may help to better model varying responses of sire progeny to environmental infection challenges for the definition of disease resilience. Data were recorded from 1999 to 2013 at a piggery in south-east Queensland, Australia (n = 31,230). Firstly, CG estimates of average daily gain (ADG) and backfat (BF) were adjusted for MaxT, MinT and Rain, which were fitted as splines. In the models used to derive CG estimates for ADG, MaxT and MinT were significant variables. The models that contained these significant climatic variables had CG estimates with a lower variance compared to models without significant climatic variables. Variance component estimates were similar across all models, suggesting that these significant climatic variables accounted for some known environmental variation captured in CG estimates. No climatic variables were significant in the models used to derive the CG estimates for BF. These CG estimates were used to categorize environments. There was no observable sire by environment interaction (Sire×E) for ADG when using the environmental descriptors based on CG estimates on BF. For the environmental descriptors based on CG estimates of ADG, there was significant Sire×E only when MinT was included in the model (p = .01). Therefore, this new definition of the environment, preadjusted by MinT, increased the ability to detect Sire×E. While the unknown challenges captured in refined CG estimates need verification for infection challenges, this may provide a practical approach for the genetic improvement of disease resilience.

Simple Summary The VetCompass Australia program collects real-time clinical records from veterinary practices and aggregates them for researchers to interrogate. It delivers Australian researchers sustainable and cost-effective access to authoritative data from hundreds of veterinary practitioners, across Australia and opens up major international collaborative opportunities with related projects in the United Kingdom and elsewhere. Abstract VetCompass Australia is veterinary medical records-based research coordinated with the global VetCompass endeavor to maximize its quality and effectiveness for Australian companion animals (cats, dogs, and horses). Bringing together all seven Australian veterinary schools, it is the first nationwide surveillance system collating clinical records on companion-animal diseases and treatments. VetCompass data service collects and aggregates real-time, clinical records for researchers to interrogate, delivering sustainable and cost-effective access to data from hundreds of veterinary practitioners nationwide. Analysis of these clinical records will reveal geographical and temporal trends in the prevalence of inherited and acquired diseases, identify frequently prescribed treatments, revolutionize clinical auditing, help the veterinary profession to rank research priorities, and assure evidence-based companion-animal curricula in veterinary schools. VetCompass Australia will progress in three phases: (1) roll-out of the VetCompass platform to harvest Australian veterinary clinical record data; (2) development and enrichment of the coding (data-presentation) platform; and (3) creation of a world-first, real-time surveillance interface with natural language processing (NLP) technology. The first of these three phases is described in the current article. Advances in the collection and sharing of records from numerous practices will enable veterinary professionals to deliver a vastly improved level of care for companion animals that will improve their quality of life.

Objective Significant proportions of horses leave the Australian Thoroughbred and Standardbred racing industries, which has ramifications for both the economic sustainability and the public perception of racing. The aim of this study was to quantify potential horse wastage, describe the destinations of exiting horses and identify risk factors for horses going to these destinations. Methods Questionnaires were sent to 1258 selected Thoroughbred and 981 Standardbred trainers, with response rates of 30% and 32%, respectively. The survey investigated the role of various risk factors for wastage, including horse age, sex and number of years in training. The destination of departing horses was also examined in relation to these risk factors. Results Total horse exit rates for the 2002–03 official race year were 39.7% and 38.7% for the Thoroughbred and Standardbred racing industries, respectively. Reasons for leaving included ‘poor performance/slow’ (36.5% Thoroughbreds, 35.2% Standardbreds), ‘illness/injury’ (31.0%, 27.1%), ‘to breed’ (9.4%, 10.1%), ‘unsuitable temperament/behaviour’ (6.4%, 6.4%) and ‘other’ (16.8%, 21.2%). Statistically significant (P < 0.001) risk factors influencing the destinations of both Thoroughbred and Standardbred racing horses included whether the trainer owned the horses, sex, age and reasons for leaving. In addition, some factors were specific to one breed or the other. Conclusions Improved behaviour training and early identification of the causes of poor performance could assist in reducing wastage.

Background : Infection is second only to cardiovascular disease as a cause of death in the haemodialysis (HD) population. Aim : To assess the effect of introducing catheter lock solution taurolidine–citrate–heparin to all tunnelled central venous catheters (TCVCs) on staphylococcal bloodstream infection rates in patients on chronic HD. Design: Observational, prospective analysis of the incidence rates of staphylococcal bacteraemic events in National Health Service (NHS) Greater Glasgow & Clyde and NHS Forth Valley between April 2011 and June 2013, with taurolidine–citrate–heparin catheter lock solution introduced July 2012. Methods: Data were collected each calendar quarter through a structured query language interrogation of the renal unit electronic patient record, with staphylococcal bacteraemic events expressed per 1000 vascular access exposed days. Comparison between pre- and post-intervention periods was made by student’s t -testing. Results : Two hundred and thirty-nine staphylococcal bacteraemic events occurred over a total of 424 835 HD days in 565 patients; 81 events in 289 389 arterio-venous fistula or graft (AVF/AVG) HD days and 158 events in 135 446 TCVC HD days. Following the introduction of taurolidine–citrate–heparin, bacteraemic events in patients dialysing via a TCVC fell from 1.59/1000 HD days to 0.69/1000 HD days, P = 0.004. The staphylococcal bacteraemia rate in AVF/AVGs remained unchanged; 0.30 vs. 0.26/1000 HD days, P = 0.52. Conclusions : Replacing heparin 5000 IU with Taurolidine–citrate–heparin as catheter lock solution was associated with a statistically significant 56% reduction in staphylococcal bloodstream infection rates in our TCVC HD population.

The emergence of an association between gadolinium-based contrast agents (GBCA) and the rare condition nephrogenic systemic fibrosis (NSF) led to a warning in 2006 from the Food and Drug Administration (FDA) restricting the use of the GBCAs to patients with an estimated glomerular filtration rate of >30 mL/min/1.73m(2) . We discuss our experience with a post-FDA restriction presentation of NSF and subsequent patient death in which the prolonged lead-time of ∼5.5 years led to challenges in ensuring a secure diagnosis of NSF and establishing risk exposures. Accurate contemporary records of contrast administration and clinical factors alongside clinical and pathological expertise ensured that we were able to confidently diagnose NSF, despite the length of lead time and confounding factors.

The success of an automatic milking system is generally reliant upon the voluntary movement of cows around the farm system and the correct management of incentives to achieve a targeted level of cow traffic. The present study investigated the effect of providing a small feed reward as an incentive at milking on the premilking voluntary waiting time of cows milked on a prototype robotic rotary in an Australian pasture-based dairy. The 2 treatments were "feed on" (concentrate offered at milking) and "feed off" (no concentrate offered at milking), with data from a single herd of 168 lactating dairy cows collected over 16d. A survival analysis with time-varying covariates was used to model the voluntary waiting times of cows in the premilking yard. The median time cows spent waiting before milking was 129 min and after 4h just over 70% of the cows had exited the yard (volunteered for milking). When feed was provided, cows were faster to exit the premilking yard (shorter time spent waiting) and waited just over half the time (0.53×) they did during the "feed off" treatment. Heifers exited the premilking yard more rapidly than cows in later lactations, with older cows spending at least 1.40 times longer in the yard before milking. Average daily milk yield along with stage of lactation and fetching cows from the paddock also influenced cow traffic in the premilking yard. As the number of cows in the premilking yard increased, voluntary waiting time also increased. At a queue length of 20 or more cows, the negative effect on waiting time of an additional cow entering the yard was less than that when fewer than 20 cows were present. Results demonstrated that feeding a small reward on the robotic rotary platform can reduce the time cows spend in the premilking yard, leading to a potential reduction in the risk of congestion at the dairy, particularly during times of high demand. Minimizing congestion will likely benefit multiple aspects of the voluntary milking operation, including a potential improvement in robot utilization, a reduction in unnecessary time spent off pasture by cows in the milking herd, promoting cow welfare through reducing the risk of lameness, and enhancing productivity. Targeting strategies to minimize queue length to less than the threshold length, which in this study was 20 cows, could result in reduced time spent in the premilking yard.

Motivation: Gene expression data exhibit common information over the genome. This article shows how data can be analysed from an efficient whole-genome perspective. Further, the methods have been developed so that users with limited expertise in bioinformatics and statistical computing techniques could use and modify this procedure to their own needs. The method outlined first uses a large-scale linear mixed model for the expression data genome-wide, and then uses finite mixture models to separate differentially expressed (DE) from non-DE transcripts. These methods are illustrated through application to an exceptional UK Brain Expression Consortium involving 12 human frozen post-mortem brain regions. Results: Fitting linear mixed models has allowed variation in gene expression between different biological states (e.g. brain regions, gender, age) to be investigated. The model can be extended to allow for differing levels of variation between different biological states. Predicted values of the random effects show the effects of each transcript in a particular biological state. Using the UK Brain Expression Consortium data, this approach yielded striking patterns of co-regional gene expression. Fitting the finite mixture model to the effects within each state provides a convenient method to filter transcripts that are DE: these DE transcripts can then be extracted for advanced functional analysis. Availability: The data for all regions except HYPO and SPCO are available at the Gene Expression Omnibus (GEO) site, accession number GSE46706. R code for the analysis is available in the Supplementary file. Contact: peter.thomson@sydney.edu.au Supplementary information: Supplementary data are available at Bioinformatics online.

A total of 600 Ross 308-day-old male broiler chicks were used in a 28 day digestibility study to investigate the interaction between dietary calcium (Ca) and non-phytate phosphorus (nPP) on the digestibility of minerals and amino acids. Diets were formulated to be nutritionally adequate except for Ca and nPP. Fifteen mash diets based on corn and soya bean meal with varying concentrations of Ca (6.4 to 12.0 g/kg) and nPP (2.4 to 7.0 g/kg) were used. Diets were clustered around total densities of Ca and nPP of 12, 13.5 or 15.0 (g/kg) and within each density, a range of five Ca : nPP ratios (1.14 : 1, 1.5 : 1, 2.0 : 1, 2.75 : 1 and 4.0 : 1) were fed. Birds had free access to feed and water throughout the study. At day 28, birds were euthanised for the determination of apparent ileal mineral and amino acid digestibility. Data were modelled in R version 2.15 using a linear mixed-effects model and interrogation of the data was performed by fitting a low order polynomial function. At high Ca concentrations, increasing nPP led to an increase in the apparent digestibility of minerals. Apparent ileal digestibility of phosphorus (P) was enhanced with increasing dietary nPP up to 5.5 g/kg beyond which no improvements were found. Maximal Ca digestibility was found in diets with >8.0 g/kg Ca with concomitant low concentrations of nPP. Diets with a broader Ca : nPP ratio improved the digestibility of Ca but were deleterious to the digestibility of P. In this study, apparent digestibility of amino acids was broadly unaffected by dietary Ca and nPP concentrations. However, interactions between Ca and nPP were observed for the digestibility of glutamine, tyrosine and methionine (all P

Testicular volume (TV) is one of the most important traits used in evaluation of the reproductive capacity of male animals. The levelled-container used in the present study was found to be reliable instrument to measure TV, based on a water displacement method. Sperm-associated antigen 11 (SPAG11) is an important gene that affects male reproductive performance. An objective of the present study, therefore, was to determine if single nucleotide polymorphisms (SNPs) in a fragment of the SPAG11 gene could be used to determine associations with values of testicular biometric variables in Boer goats. Primers were designed to amplify the full length of the first two exons of SPAG11. The targeted fragment was generated using a molecular cloning technique. As the result, four SNPs, [g.1256A > G(ss19199134542), g.1270C > T(ss19199134541), g.1325A > G(ss19199134540) and g.1327 G > A (ss19199134543)], were detected using a single-base extension (SBE) method. Two of these SNPs were synonymous (ss19199134540 and ss19199134542). The other two SNPs were nonsynonymous, thus, there were changes in amino acid in the resulting protein: threonine to isoleucine (for ss19199134541) and arginine to glutamine (for ss19199134543). The SNP ss19199134543 was the only locus detected that was associated with TV (P = 0.002). None of the testes dimensions nor TW were associated with detected SPAG11 gene SNPs. Most likely, the ss19199134543 locus affects tissue structures adjacent to the testes, causing the change in TV. In conclusion, among the studied testicular biometric variables, TV had the greatest potential for preselecting of bucks with desirable semen quality. The use of the levelled-container as a TV measurement approach was an accurate and reliable method.

Smallholder large ruminant production in Lao People's Democratic Republic (Laos) is characterised by low reproductive efficiency. To determine if common abortifacient bovid infectious diseases are involved, a serological investigation was conducted. Sera was collected from stored and fresh cattle (n = 390) and buffalo (n = 130) samples from 2016-18 from, and then examined for associations in a retrospective risk factor study of 71 herds. The sera were assayed for antibodies to Neospora caninum, bovine viral diarrhoea virus (BVDV), Leptospira interrogans serovar Hardjo and Brucella abortus using commercially available enzyme-linked immunosorbent assay kits. These pathogens were detected in buffalo samples at 78.5% (95% CI 71.4-85.6), 0%, 2.3% (95% CI 0-4.9) and 0%, respectively, and in cattle at 4.4% (95% CI 2.4-6.4), 7.7% (95% CI 3.1-12.3), 12.8% (95% CI 9.5-16.1) and 0.26% (95% CI 0-0.8), respectively. Exposure of buffalo to N. caninum was positively associated with buffalo age, with a predicted seropositivity at birth of 52.8%, increasing to 97.2% by 12 years of age (p = 0.037). Exposure of cattle to L. interrogans serovar Hardjo was more prevalent in females compared to males, was associated with higher titres of BVDV, and was more prevalent in the wet season compared to the dry season. Exposure of cattle to BVDV was more prevalent in males compared to females, the wet and dry seasons were comparable, and was associated with rising antibody titres against N. caninum and L. interrogans serovar Hardjo. The risk factor survey identified that the probability of herds being N. caninum positive increased with farmer age, if farmers believed there were rodents on farm, and if farmers weren't aware that canids or rodents could contaminate bovid feed on their farm. The probability of a herd being positive to L. interrogans serovar Hardjo increased on farms where multiple cows shared the same bull, where farmers had lower husbandry knowledge, and on farms that used water troughs. The probability of a herd being BVDV seropositive increased with increasing herd size and increasing titres to N. caninum. The benchmarking of bovid exposure to emerging abortifacient pathogens and identification of their risk factors potentially informs disease prevention strategies, supporting efforts to establish a biosecure beef supply for enhanced smallholder livestock productivity, public health and food security in Laos and surrounding countries.

Background The prevalence for chronic kidney disease (CKD) in dogs varies widely (0.05–3.74%). Identified risk factors include advancing age, specific breeds, small body size, and periodontal disease. Hypothesis/Objectives To estimate the prevalence and identify risk factors associated with CKD diagnosis and survival in dogs. Purebred dogs were hypothesized to have higher CKD risk and poorer survival characteristics than crossbred dogs. Animals A merged clinical database of 107,214 dogs attending 89 UK veterinary practices over a 2-year period (January 2010–December 2011). Methods A longitudinal study design estimated the apparent prevalence (AP) whereas the true prevalence (TP) was estimated using Bayesian analysis. A nested case-control study design evaluated risk factors. Survival analysis used the Kaplan-Meier survival curve method and multivariable Cox proportional hazards regression modeling. Results The CKD AP was 0.21% (95% CI: 0.19–0.24%) and TP was 0.37% (95% posterior credibility interval 0.02–1.44%). Significant risk factors included increasing age, being insured, and certain breeds (Cocker Spaniel, Cavalier King Charles Spaniel). Cardiac disease was a significant comorbid disorder. Significant clinical signs included halitosis, weight loss, polyuria/polydipsia, urinary incontinence, vomiting, decreased appetite, lethargy, and diarrhea. The median survival time from diagnosis was 226 days (95% CI 112–326 days). International Renal Interest Society stage and blood urea nitrogen concentration at diagnosis were significantly associated with hazard of death due to CKD. Conclusions and Clinical Importance Chronic kidney disease compromises dog welfare. Increased awareness of CKD risk factors and association of blood biochemistry results with survival time should facilitate diagnosis and optimize case management to improve animal survival and welfare.

Summary The pursuits of white features and white fleeces free of pigmented fibre have been important selection objectives for many sheep breeds. The cause and inheritance of non-white colour patterns in sheep has been studied since the early 19th century. Discovery of genetic causes, especially those which predispose pigmentation in white sheep, may lead to more accurate selection tools for improved apparel wool. This article describes an extended QTL study for 13 skin and fibre pigmentation traits in sheep. A total of 19 highly significant, 10 significant and seven suggestive QTL were identified in a QTL mapping experiment using an Awassi × Merino × Merino backcross sheep population. All QTL on chromosome 2 exceeded a LOD score of greater than 4 (range 4.4–30.1), giving very strong support for a major gene for pigmentation on this chromosome. Evidence of epistatic interactions was found for QTL for four traits on chromosomes 2 and 19. The ovine TYRP1 gene on OAR 2 was sequenced as a strong positional candidate gene. A highly significant association (P

This study investigated conception rates and other reproductive outcomes achieved with artificial insemination (AI) of nulliparous Holstein heifers using sexed and conventional semen in a commercial Australian dairy herd in central western New South Wales from January 2004 to April 2009. Retrospective data from on-farm records of 9,870 inseminations of 4,456 heifers were analyzed using several mixed models to assess the effect of temperature and humidity surrounding breeding, insemination sire, artificial insemination technician, service number, and heifer weight and age at breeding on reproductive traits (conception rates, sex ratios, gestation length, and abortion and stillbirth rates). Semen was used from 15 sexed sires and 41 unsexed sires. Sexed semen was primarily used at first and second service. Empirical conception rates of 31.6 and 39.6% were achieved for sexed and unsexed semen respectively, whereas model-based predictions were lower, at 21.3 and 32.1%. Conception rates were significantly affected by insemination sire, sex-sorting, heifer age at breeding, temperature and humidity surrounding breeding, service number, and AI technician. Sexed semen yielded 86% heifers, compared with 48% for conventional semen. Significant predictors of calf sex included semen sexing, gestation length, and insemination sire. Twinning rate was high, at 3.6% for both semen types, and gestation length and heifer weight at breeding were significant predictors of twinning. Abortion rates for sexed and unsexed conceptions were similar at 6.1 and 6.5%, respectively, and were affected by heifer age at breeding. Stillbirth rate was affected by calf sex, twinning, gestation length, and AI technician; semen sorting, age at breeding, and temperature and humidity were marginally significant predictors. No abnormalities were observed in the development of offspring, except for a marginally higher stillbirth rate for sexed calves, a finding that needs further investigation. Many variables influence the breeding outcomes associated with the application of sex-sorted sperm on commercial dairy farms. Recognition and management of these variables will increase the economic return from the investment in sex-sorted sperm.

Bovine tuberculosis (BTB) is a considerable threat to livestock keepers and public health in many developing and underdeveloped countries. We investigated associations between 20 microsatellite markers and three phenotypes for BTB in a sample of the Chadian cattle population. The phenotypes measured were: 1) single intra-dermal comparative cervical tuberculin test (SICCT) performed on live animals, 2) presence of lesion post-slaughter, 3) a bacteriological tissue culture test for Mycobacterium bovis using the samples with observed lesions and 4) a predicted Bayesian model (BM) estimate of a true BTB disease status using all tested animals. All traits were recorded in binary form and as either 1 = presence or 0 = absence. A total of 224 animals for SICCT, lesion and BM traits and 96 animals with bacteriological culture test were genotyped. Generalised linear models were fitted to the binary BTB phenotypes that consisted of age (covariate), sex (2 levels), breed (2 levels) and markers (alleles: 5 - 14 levels) as explanatory variables and implemented in R using glm with a logit link function. The model was fitted for each marker, separately. Six out of 20 markers tested were significantly associated with at least one trait considered; these were ILSTS005, ILSTS006, TGLA227, BM2113 and CSRM66. Genomic regions around these markers may serve as a basis for further functional investigations. This is the first study to report association of microsatellite markers with bovine tuberculosis traits in African or Chadian cattle population.

Background.Primary focal segmental glomerulosclerosis (FSGS) is one of the commonest causes of glomerular disease and if left untreated will often progress to established renal failure. In many cases the best treatment option is renal transplantation; however primary FSGS may rapidly recur in renal allografts and may contribute to delayed graft function. We present a case of primary nonfunction in a renal allograft due to biopsy-proven FSGS.Case Report.A 32-year-old man presented with serum albumin of 22 g/L, proteinuria quantified at 12 g/L, and marked peripheral oedema. Renal biopsy demonstrated tip-variant FSGS. Despite treatment, the patient developed progressive renal dysfunction and was commenced on haemodialysis. Cadaveric renal transplantation was undertaken; however this was complicated by primary nonfunction. Renal biopsies failed to demonstrate evidence of acute rejection but did demonstrate clear evidence of FSGS. The patient was treated to no avail.Discussion.Primary renal allograft nonfunction following transplantation is often due to acute kidney injury or acute rejection. Recurrent FSGS is recognised as a phenomenon that drives allograft dysfunction but is not traditionally associated with primary nonfunction. This case highlights FSGS as a potentially aggressive process that, once active in the allograft, may prove refractory to targeted treatment. Preemptive therapies in patients deemed to be at high risk of recurrent disease may be appropriate and should be considered.

Chiari-like malformation/syringomyelia (CM/SM) in dogs describes a developmental disorder that can cause pain and reduced quality of life. This retrospective study aimed to report the period prevalence, clinical signs and risk factors for diagnosis of symptomatic CM/SM in the veterinary primary-care setting using a cross-sectional design. The study population included all dogs within the VetCompass Programme (September 1, 2009–June 13, 2014). Overall, the period prevalence of symptomatic CM/SM was 0.05 per cent (95 per cent CI 0.04 per cent to 0.06 per cent) for all breeds. The period prevalence in the Cavalier King Charles Spaniel (CKCS) was 1.6 per cent (95 per cent CI 1.2 to 2.06). Other breeds at increased odds included the King Charles Spaniel (KCS), Affenpinscher, Chihuahua and Pomeranian. Insured dogs had 4.6 times the odds (95 per cent CI 2.95 to 7.17) of having a diagnosis of CM/SM compared with uninsured dogs. Pain was the most commonly associated clinical sign (67 dogs, 72 per cent). Analgesics were prescribed to 72 (77.4 per cent) of the symptomatic dogs. Despite its low overall period prevalence, the high proportion of affected dogs identified with chronic pain suggests a significant welfare issue. Financial implications could impede the diagnostic process and lead to underestimation of the true prevalence. This study may help to inform clinicians about the clinical relevance and the need for improved awareness of clinical signs, particularly in high-risk breeds, to optimise the management of CM/SM in primary-care practice.

Gilt progeny have lighter weaning weights and greater postweaning medication and mortality rates compared with the progeny of older parity sows. Because weaning weight has been positively correlated with postweaning survival, this study aimed to determine whether the provision of supplemental milk preweaning could improve weaning weight and subsequent weights as well as postweaning survival of gilt progeny. The study was replicated in summer and winter as the effects of supplemental milk were expected to vary with season. The progeny of 80 gilts (parity 0) and 80 sows (parity 2 to 5) were allocated to both treatments: with or without supplemental milk in these 2 seasons with 5 sheds/season. Litter size was standardized (10 to 11 piglets) and each piglet was weighed at birth, d 21, weaning (4 wk), and 10 wk of age. Medications and mortalities were recorded both preweaning and postweaning. Pigs were housed within treatment groups postweaning, and ADFI and G:F were measured. Gilt progeny were 200 g lighter at birth in both replicates (P 0.05). Supplemental milk disappearance (the daily difference between the volume of milk provided and the residue left in the drinker) was greater in summer than winter (by 130 mL/piglet d(-1); P 0.05). The hypothesis that supplemental milk provision did increase gilt progeny weaning weight was supported (especially in summer) but the supplementation had no effect on postweaning weights and survival. Efforts to improve gilt progeny postweaning growth and survival need to be aimed at improving health and immunity, not just weaning weight.

Summary Reasons for performing study Studies of Thoroughbred racing populations have provided evidence of a positive effect on racing careers for horses that commence racing as 2-year-olds. Currently, research investigating the presence of this effect in the Australian Thoroughbred racing population is limited. Objectives To investigate the association between age at first start and career length in the Australian Thoroughbred population and estimate the risk of racing retirement for horses racing in Australia based on age at first start, career earnings, number of starts as a 2-year-old and distance raced. Methods Data were collected for Thoroughbreds, born on or after 1 January 1998, that had raced between 1 August 2000 and 22 February 2011 in Australia. A Kaplan–Meier survival curve, stratified by age group, was produced for career length. A Cox proportional hazard model was fitted to assess factors influencing the risk of retirement from racing. The model included sex, age at first start, career earnings, number of starts as a 2-year-old, distance raced and appropriate interaction terms. Results The study population included 117,088 horses. Geldings had significantly (P

Significant variation exists for maternal nurturing ability in inbred mice. Although classical mapping approaches have identified quantitative trait loci (QTL) that may account for this variation, the underlying genes are unknown. In this study, lactation performance data among the mouse diversity panel were used to map genomic regions associated with this variation. Females from each of 32 inbred strains ( n = 8–19 dams/strain) were studied during the first 8 days of lactation by allowing them to raise weight- and size-normalized cross-foster litters (10 pups/litter). Average daily weight gain (ADG) of litters served as the primary indicator of milk production. The number of pups successfully reared to 8 days (PNUM8) also served as a related indicator of maternal performance. Initial haplotype association analysis using a Bonferroni-corrected, genome-wide threshold revealed 10 and 15 associations encompassing 11 and 13 genes for ADG and PNUM8, respectively. The most significant of these associated haplotype blocks were found on MMU 8, 11, and 19 and contained the genes Nr3c2, Egfr, Sec61g, and Gnaq. Lastly, two haplotype blocks on MMU9 were detected in association with PNUM8. These overlapped with the previously described maternal performance QTL, Neogq1. These results suggest that the application of in silico QTL mapping is a useful tool in discovering the presence of novel candidate genes involved in determining lactation capacity in mice.

Summary An advanced intercross line (AIL) is an easier and more cost-effective approach compared to recombinant inbred lines for fine mapping of quantitative trait loci (QTL) identified by F2 designs. In an AIL, a complex binary trait can be mapped through analysis of either continuously distributed proxy traits for the liability of the binary trait or the liability itself, the latter presenting the greater statistical challenge. In another work, we successfully applied both approaches in an AIL to fine map previously identified QTL underlying anatomical parameters of the cardiac inter-atrial septum including patent foramen ovale. Here, we describe the statistical methods that we used to analyse complex binary traits in our AIL design. This is achieved using a likelihood-based method, with the expectation–maximisation algorithm allowing use of standard logistic regression methods for model fitting.

Several studies have assessed different components of lateralization. To date, the relationships between the 3 measures of laterality, structural, motor, and sensory, have not widely been assessed. Specifically, the relationships between structural (hair whorl characteristics) and motor or sensory lateralization have largely been overlooked. This study investigated the associations between these measures of lateralization in dogs (n = 114), using hair whorl characteristics (structural), the Kong and First-stepping Tests (motor), and the Sensory Jump Test (sensory). Several associations emerged, revealing the first evidence of a relationship between structural asymmetry (both the presence and direction of a hair whorl in various regions of the body) and sensory lateralization. Specifically, the presence of a whorl on the dog's left side of the head (cephalic) and thorax was associated with a right visual bias. In addition, right visual bias was probable if the ventral mandibular whorl was present in a counter-clockwise direction ( P = 0.008). Our data also demonstrated an association between structural and motor laterality (paw preference). Most notably, dogs with clockwise chest whorls were significantly more right-preferent in the First-stepping Test than those with counter-clockwise whorls ( P = 0.010). In addition, an association between measures of motor and sensory lateralization also emerged, representing some of the first evidence of such a relationship in nonhuman animals.

Microarray studies are now common for human, agricultural plant and animal studies. False discovery rate (FDR) is widely used in the analysis of large-scale microarray data to account for problems associated with multiple testing. A well-designed microarray study should have adequate statistical power to detect the differentially expressed (DE) genes, while keeping the FDR acceptably low. In this paper, we used a mixture model of expression responses involving DE genes and non-DE genes to analyse theoretical FDR and power for simple scenarios where it is assumed that each gene has equal error variance and the gene effects are independent. A simulation study was used to evaluate the empirical FDR and power for more complex scenarios with unequal error variance and gene dependence. Based on this approach, we present a general guide for sample size requirement at the experimental design stage for prospective microarray studies. This paper presented an approach to explicitly connect the sample size with FDR a...

The processes regulating the complex neurodegenerative cascade of vacuolation, neuroinflammation, neuronal loss and myelin deficits in fucosidosis, a neurological lysosomal storage disorder, remain unclear. To elucidate these processes the gene expression profile of the cerebral cortex from untreated and intrathecal enzyme replacement therapy treated fucosidosis pups and age-matched unaffected controls were examined. Neuroinflammation and cell death processes were identified to have a major role in fucosidosis pathophysiology with 37% of differentially expressed (DE) genes involved in these processes. Critical, specific, early decreases in expression levels of key genes in myelin assembly were identified by gene expression profiling, including myelin-associated glycoprotein (MAG), myelin and lymphocyte protein (MAL), and oligodendrocyte myelin paranodal and inner loop protein (OPALIN). These gene expression changes may be indicative of early neuronal loss causing reduced electrical impulses required for oligodendrocyte maturation.

While standard techniques are available for the analysis of time-series (longitudinal) data, and for ordinal (rating) data, not much is available for the combination of the two, at least in a readily-usable form. However, this data type is common place in the natural and health sciences where repeated ratings are recorded on the same subject. To analyse these data, this paper considers a transition (Markov) model where the rating of a subject at one time depends explicitly on the observed rating at the previous point of time by incorporating the previous rating as a predictor variable. Complications arise with adequate handling of data at the first observation (t=1), as there is no prior observation to use as a predictor. To overcome this, it is postulated the existence of a rating at time t=0; however it is treated as ‘missing data’ and the expectation–maximisation algorithm used to accommodate this. The particular benefits of this method are shown for shorter time series.

OBJECTIVE Compare the career profiles of a cohort of Standardbred horses that first raced as 2-year-olds with those that started their racing careers at a later age. METHOD Retrospective analysis of the racing records of all foals born in New South Wales in the 2000 foaling season. RESULTS The career records of 999 horses were analysed. Almost half (43.9%) first raced as 2-year-olds and one-third (33.9%) as 3-year-olds. The median career duration for horses that first raced as 2-year-olds was 2.93 years (interquartile range (IQR) 2.70-3.16), which was significantly greater than the median for horses that first raced at 3, 4 or ≥5 years old (P < 0.001). Males, and horses that first raced as 2-year-olds, earned significantly more prize money than females or horses that started racing aged ≥3 years (P < 0.001). The population median number of career starts was 28.0 (IQR 8-64). Males, and horses that first raced as 2-year-olds, had significantly more career starts than females or horses that started racing aged ≥3 years (P < 0.001). CONCLUSION This study found no evidence suggesting that racing as a 2-year-old had a deleterious effect on a horse's racing career.

Canine hip dysplasia (CHD) is a multifactorial skeletal disorder which is very common in pedigree dogs and represents a huge concern for canine welfare. Control schemes based on selective breeding have been in operation for decades. The aim of these schemes is to reduce the impact of CHD on canine welfare by selecting for reduced radiographic evidence of CHD pathology as assessed by a variety of phenotypes. There is less information regarding the genotypic correlation between these phenotypes and the impact of CHD on canine welfare. Although the phenotypes chosen as the basis for these control schemes have displayed heritable phenotypic variation in many studies, success in achieving improvement in the phenotypes has been mixed. There is significant room for improvement in the current schemes through the use of estimated breeding values (EBVs), which can combine a dog's CHD phenotype with CHD phenotypes of relatives, other phenotypes as they are proven to be genetically correlated with CHD (especially elbow dysplasia phenotypes), and information from genetic tests for population-relevant DNA markers, as such tests become available. Additionally, breed clubs should be encouraged and assisted to formulate rational, evidenced-based breeding recommendations for CHD which suit their individual circumstances and dynamically to adjust the breeding recommendations based on continuous tracking of CHD genetic trends. These improvements can assist in safely and effectively reducing the impact of CHD on pedigree dog welfare.

Marsupials provide a suitable alternative model to studying mammary gland involution. They have evolved a different reproductive strategy from eutherians, giving birth to an altricial young and secreting milk that changes in composition during lactation. In this study, we used a marsupial-specific EST microarray to identify 47 up-regulated genes during mammary gland involution in the tammar wallaby (Macropus eugenii). These include the pro-apoptotic tumour necrosis factor receptor superfamily 21 (TNFRSF21) gene, whose expression in the mammary gland has not previously been reported. Genes encoding putative novel milk proteins which may protect the mammary gland from infection were also found to be up-regulated, such as amiloride binding protein 1 (ABP1), complement component 1QB (C1QB), complement component 4A (C4A) and colony stimulating factor 2 receptor β (CSF2Rβ). Our results show that the marsupial reproductive strategy was successfully exploited to identify genes and putative novel milk proteins implicated in mammary gland involution.

A range of mobility aids are available to assist people living with vision impairment, and of these, guide dog ownership offers them several unique benefits. However, training a dog to be a successful guide dog comes at a high cost (approximately AU$30,000). Therefore, the aim of this study was to determine whether temperament testing and kennel behavior measures could be used by Guide Dog Organizations for the early identification of dogs suitable for guiding work and thus to reduce production costs. Temperament tests (Passive and Noise, Sudden Appearance, and Dog Distraction Tests) and kennel behavior assessments (Activity Level, Salivary Immunoglobulin A Concentration, and Kennel Surveillance) were assessed in potential guide dogs (n = 25-113) at the Guide Dogs NSW/ACT Training Centre, Glossodia, New South Wales, Australia. Several significant predictors of guide dog success were identified. The presence of panting (P = 0.029) and licking (P = 0.005) when contrasted with baseline observations in the Dog Distraction Test, significantly reduced the probability of guide dog success. Success was also reduced with the latency for a dog to sit in the third Noise Test (P = 0.028), and when the time spent resting was reduced during the evening period (P = 0.018) in the Kennel Surveillance assessment. This study reports that 4 specific behavioral responses, which may reflect anxiety and restlessness, predict low suitability of dogs for guiding work. Through the identification of early predictors of guide dog success, resources can be more appropriately focused on dogs with a higher probability of success, whereas unsuitable dogs can be rehomed.

Summary Canine hip dysplasia (CHD) is a common and debilitating developmental condition of the canine coxofemoral (hip) joint, exhibiting a multifactorial pattern of inheritance. British Veterinary Association hip traits (BVAHTs) are nine radiographic features of hips used in several countries to ordinally score both the right and left hip of potential breeding candidates to assess their suitability for breeding. The objective of this study was to examine some aspects of the relationship between contralateral scores for each BVAHT in a cohort of 13 124 Australian-registered German Shepherd Dogs. Goodman and Kruskal gamma coefficients of 0.48–0.95 and correlation coefficients of 0.50–0.74 demonstrate that the association between right and left hip scores varies between moderate and strong for BVAHTs. Principal component analysis of scores detected a sizeable left-versus-right effect, a finding supported by symmetry and quasi-symmetry analyses which found that seven of the nine BVAHTs display significant marginal asymmetry. Dogs showing asymmetry for one BVAHT are significantly more likely to display asymmetry at other BVAHTs. When asymmetry is expressed as a binary trait (either symmetrical or asymmetrical), it displays low to moderate heritability. Estimates of genetic correlations between right and left scores are very high for all BVAHTs (>0.945), suggesting right and left scores for each BVAHT are largely determined by the same set of genes. The marginal asymmetries are therefore more likely to be of environmental and non-additive genetic origin. In breeding programmes for CHD, we recommend that scores from both hips be used to estimate breeding values, with a term for side-of-hip included in the model to account for score variation owing to asymmetry.

Background: Hemodialysis catheter thrombosis is associated with loss of catheter patency, catheter-related bacteremia and sepsis. To limit these risks, many renal units use heparin as a catheter-locking solution. In this study we investigate the effect of different concentrations of heparin catheter lock solution on systemic anticoagulation in an investigator-blinded randomized study of patients with non-tunneled (temporary) central venous catheters. Methods: 28 consecutive patients requiring insertion of a temporary non-tunneled dual lumen central venous hemodialysis catheter were randomly allocated to receive either heparin 5,000 IU/ml or heparin 1,000 IU/ml as catheter lock solutions. The primary outcome measure was the difference in activated partial thromboplastin time (APTT) at 10 minutes following catheter locking with heparin 5,000 IU/ml and heparin 1,000 IU/ml. Secondary outcomes included intradialytic blood flow rates, catheter removal due to insufficient hemodialysis blood flow to maintain hemodialysis and catheter-related bacteremia. Results: 13 patients were randomized to the heparin 1,000 IU/ml group with 15 patients randomized to the heparin 5,000 IU/ml group. There was a statistically significant increase in APTT at 10 minutes between groups with median +22.2% (range 0 ― 210) rise in APTT in the heparin 1,000 IU/ml group compared with +373.7% (range 133 ― 800) in the heparin 5,000 IU/ml group (p < 0.001). There was no statistically significant difference between groups with the secondary outcomes of intradialytic blood flow, catheter failure rates and catheter-related bacteremia rates. Conclusions: Heparin 1,000 IU/ml catheter lock solution confers a significantly lower risk of systemic heparinization than heparin 5,000 IU/ml without any overtly detrimental effect on intradialytic blood flow, catheter failure rates and catheter-related bacteremia rates.

Background The mulesing procedure is the main procedure used to control breech flystrike of sheep in Australia, but other permanent methods of altering breech conformation are currently being investigated and wound healing is an important component of that comparative assessment. Objective To qualitatively assess the gross and microscopic tissue damage and wound healing that occurs in the immediate post-treatment period after mulesing, intradermal-cetrimide treatment and clip application. Method The study group of 30 mulesed, 30 cetrimide-treated, 30 control and 10 clip-treated sheep were humanely killed at six time points during the 3–47 days post treatment. Treatment sites and wound beds were examined grossly and microscopically. Results Mulesing wounds healed rapidly in a predictable manner, producing long linear scars on either side of the breech and tail by 32–47 days post treatment. Although the time course for healing post cetrimide-treatment was similar to that for mulesing, complications occurred and included inadequate wound healing because of persistence of adherent necrotic tissue, poor skin tightening around the tail, and patchy or deep penetration of the cetrimide resulting in necrosis of adjacent skin and deeper structures. The clips resulted in skin tightening around the ventrolateral breech and tail, although the formation of skin tags and clip slippage were of concern in some sheep. Conclusion Wounds healed rapidly after mulesing with minimal complications. The intradermal-cetrimide treatment appeared to produce imperfect and sometimes delayed wound healing compared with mulesing. The clips resulted in comparable wound healing to mulesing, but further field trials are required to assess their effectiveness in flystrike prevention.

Background Mulesing is an important method of preventing flystrike of Merino sheep in Australia, but because there are important short-term welfare issues associated with mulesing, alternative methods of removing the skin folds for breech flystrike prevention are being investigated. Objective To examine the short-term systemic effects of mulesing and two proposed alternatives, compared with two control methods, for controlling breech flystrike. Method The five treatment groups comprised 10 lambs each: (1) mulesing, (2) intradermal-cetrimide treatment, (3) clip application, (4) tail docking only and (5) no treatment. Changes in body weight, haematological and biochemical profiles, and concentrations of fibrinogen, haptoglobin and serum amyloid A were measured repeatedly for 29 days post treatment. Results The mulesing and intradermal-cetrimide groups were the only treatment groups to lose weight during the first week, with greater weight loss in the mulesing group. The mulesing group had the most marked increases in all three acute-phase protein concentrations, closely followed by the intradermal-cetrimide group, with a mild increase observed for the clip group and even less for the tail-docked group. The mulesing group was the only group to develop mild anaemia, transient hyperglycaemia and a persistent decreased albumin : globulin ratio. The neutrophil : lymphocyte ratio was above the upper reference limit for both the mulesing and intradermal-cetrimide groups. Conclusion Mulesing had the greatest systemic effect in terms of the magnitude and duration of increased acute-phase protein concentrations and haematological, biochemical and body weight changes. The clips had a significantly reduced systemic effect compared with mulesing, with the intradermal-cetrimide treatment in between the two. Tail docking had a minimal systemic effect.

An experiment was conducted to measure the effect of diet on circulating concentrations of metabolic hormones and metabolites in cows undergoing extended lactations. Two groups of 6 Holstein-Friesian cows managed for lactations of 670 d were used in the experiment. One group was fully fed on a total mixed ration (TMR), whereas the other group grazed fresh pasture supplemented with grain (P+G). On 7 occasions between 332 and 612 d in milk, concentrations of metabolic hormones and glucose were measured in the blood plasma of each cow. Cows fed TMR gained more weight and body condition than P+G cows, but did not produce more milk during the study period. Only 3 of the TMR cows continued to lactate until 612 d in milk compared with all 6 of the P+G cows. Blood plasma from cows fed TMR had higher concentrations of glucose, insulin, glucagon, insulin-like growth factor 1, and leptin, but lower concentrations of growth hormone, than that from P+G cows. These changes were consistent with the preferential deposition of energy into adipose tissue at the expense of milk production and presumably were induced by a diet that provided precursors for gluconeogenesis that were in excess of the requirements for maintenance and prevailing milk production. The mechanism responsible for some TMR cows putting on excess weight and reducing or ceasing milk production is uncertain, but this observation has important implications for the nutritional management of cows in extended lactation programs.

Motor laterality in potential guide dogs (n = 113) was determined using two methods: the Kong™ Test (the current benchmark test) and our innovation, a First-stepping Test. Kong™ studies record paw use during foraging from a rubber cylinder. However, motivation to feed varies markedly among dogs and breeds, and the test comprises 50 observations which for a single dog can take up to 4 hours to collect. The First-stepping Test bypasses hunger, and simply records the first foot advanced after standing with both forelegs level. In contrast to the Kong™ Test, it allows 50 observations to be gathered in 20 minutes. The findings of the current study indicate that lateralized behavior in the domestic dog is strongly task-dependent. The First-stepping Test revealed more significant paw preferences (PPs) than the Kong™ Test (76.1% vs. 52.2%). A significant right population bias ( P = 0.036) was revealed using this novel test, whereas there was no bias in the direction of laterality observed using the Kong™ Test ( P = 0.30). Instead, there was a significant population bias for the category of ambidextrous PP using the Kong™ ( P = 0.005). Strength of laterality (regardless of direction) was significantly high in the First-stepping Test ( P 0.001), but only weak PPs were observed for the Kong™ Test ( P = 0.65). Measures of laterality from the First-stepping Test were not influenced by dog factors, whereas age, breed, and sex of the dog were significantly associated with several laterality measures during the Kong™ Test. The occurrence of using both paws simultaneously to either hold the Kong™, or to step-off by means of jumping, was associated with a decrease in lateral strength for both tests. The First-stepping Test was repeatable, and the intraobserver (κ = 0.988) and interobserver (κ = 0.975) reliabilities were high. It offers a simple, quick and, when compared with the Kong™ Test, a more discriminative method of determining PP that is less influenced by dog factors.

Sensory lateralization in dogs (n = 74) was investigated in this study using our innovation, the Sensory Jump Test. This required the modification of head halters to create three different ocular treatments (binocular, right, and left monocular vision) for eye preference assessment in a jumping task. Ten jumps were recorded as a jump set for each treatment. Measurements recorded included ( i ) launch and landing paws, ( ii ) type of jump, ( iii ) approach distance, ( iv ) clearance height of the forepaw, hindpaw, and the lowest part of the body to clear the jump, and ( v ) whether the jump was successful. Factors significantly associated with these jump outcomes included ocular treatment, jump set number, and replication number. Most notably, in the first jump set, findings indicated a left hemispheric dominance for the initial navigation of the Sensory Jump Test, as left monocular vision (LMV) compromised of jumping more than right monocular (RMV) and binocular vision, with a significantly reduced approach distance and forepaw clearance observed in dogs with LMV. However, by the third jump set, dogs undergoing LMV launched from a greater approach distance and with a higher clearance height, corresponding to an increase in success rate of the jump, in comparison with RMV and binocular vision dogs. A marginally non-significant RMV bias was observed for eye preference based on the laterality indices for approach distance ( P = 0.060) and lowest body part clearance height ( P = 0.067). A comparison between eye preference and launching or landing paws showed no association between these measures of sensory and motor laterality. To our knowledge, this is the first study to report on sensory lateralization in the dog, and furthermore, to compare both motor and sensory laterality in dogs.

The Chronic Kidney Disease (CKD) Prognosis Consortium is a collaborative author of the above-mentioned article. The CKD Prognosis Consortium investigators/collaborators are as follows: • African American Study of Kidney Disease and Hypertension (AASK): Brad Astor, Lawrence J. Appel; British Columbia CKD Study (BC CKD): Adeera Levin, Ognjenka Djurdjev; Canadian Study of Prediction of Death, Dialysis and Interim Cardiovascular Events (CanPREDDICT): Adeera Levin, Mila Tang, Ognjenka Djurdjev; Cleveland Clinic CKD Registry Study (CCF): Sankar D. Navaneethan, Stacey E. Jolly, Jesse D. Schold, Joseph V. Nally Jr; Chronic Renal Impairment in Birmingham (CRIB): David C. Wheeler, Jonathan Emberson, John Townend, Martin Landray; Chronic Renal Insufficiency Cohort Study (CRIC): Harold I. Feldman, Chi-yuan Hsu, James P. Lash, Lawrence J. Appel; Chronic Renal Insufficiency Standards Implementation Study (CRISIS): Philip A. Kalra, James P. Ritchie, Raman Maharajan, Helen Alderson, Beverly Lane; German Chronic Kidney Disease Study (GCKD): Kai-Uwe Eckardt, Markus P. Schneider, Anna Kottgen, Florian Kronenberg, Barbara Barthlein; Geisinger Health System: Alex R. Chang, Jamie A. Green, H. Lester Kirchner, Kevin Ho; Grampian Laboratory Outcomes, Morbidity and Mortality Studies – 2 (GLOMMS2): Angharad Marks, Corri Black, Gordon J. Prescott, Nick Fluck; Gonryo Study: Masaaki Nakayama, Mariko Miyazaki, Tae Yamamoto, Gen Yamada; Hong Kong CKD Studies: Angela Yee-Moon Wang, Sharon Cheung, Sharon Wong, Jessie Chu, Henry Wu; Maccabi Health System: Varda Shalev, Gabriel Chodick; Multifactorial Approach and Superior Treatment Efficacy in Renal Patients with the Aid of a Nurse Practitioner (MASTERPLAN): Peter J. Blankestijn, Jack F.M. Wetzels, Arjan D. van Zuilen, Jan A. van den Brand; Modification of Diet in Renal Disease Study (MDRD): Andrew S. Levey, Lesley A. Inker, Mark J. Sarnak, Hocine Tighiouart; Nanjing CKD Network Cohort Study (Nanjing CKD): Haitao Zhang; NephroTest Study: Benedicte Stengel; National Renal Healthcare Program – Uruguay (NRHP-URU): Pablo G. Rios, Nelson Mazzuchi, Liliana Gadola, Veronica Lamadrid, Laura Sola; New Zealand Diabetes Cohort Study (NZDCS): John F. Collins, C. Raina Elley, Timothy Kenealy; Parcours de Soins des Personnes Agees (PSPA): Olivier Moranne, Cecile Couchoud, Cecile Vigneau; Primary-Secondary Care Partnership to Prevent Adverse Outcomes in Chronic Kidney Disease (PSP CKD): Nigel J. Brunskill, Rupert W. Major, David Shepherd, James F. Medcalf; Racial and Cardiovascular Risk Anomalies in CKD Cohort (RCAV): Csaba P. Kovesdy, Kamyar Kalantar-Zadeh, Miklos Z. Molnar, Keiichi Sumida, Praveen K. Potukuchi; Reduction of Endpoints in Non-insulin Dependent Diabetes Mellitus with the Angiotensin II Antagonist Losartan (RENAAL): Hiddo J.L. Heerspink, Dick de Zeeuw, Barry Brenner; Stockholm CREAtinine Measurements Cohort (SCREAM): Juan Jesus Carrero, Peter Barany, Abdul Rashid Qureshi, Carl-Gustaf Elinder; Second Manifestations of ARTerial Disease Study (SMART): Frank L.J. Visseren, Yolanda van der Graaf; Swedish Renal Registry CKD Cohort (SRR CKD): Marie Evans, Maria Stendahl, Staffan Schon, Marten Segelmark, Karl-Goran Prutz; Sunnybrook Cohort: David M. Naimark, Navdeep Tangri; West of Scotland CKD Study: Patrick B. Mark, Jamie P. Traynor, Colin C. Geddes, Peter C. Thomson.• CKD Prognosis Consortium Steering Committee: Alex R. Chang, Josef Coresh (Chair), Ron T. Gansevoort, Morgan E. Grams, Anna Kottgen, Andrew S. Levey, Kunihiro Matsushita, Mark Woodward, Luxia Zhang.• CKD Prognosis Consortium Data Coordinating Center: Shoshana H. Ballew (Assistant Project Director), Jingsha Chen (Programmer), Josef Coresh (Principal Investigator), Morgan E. Grams (Director of Nephrology Initiatives), Lucia Kwak (Programmer), Kunihiro Matsushita (Director), Yingying Sang (Lead Programmer), Aditya Surapaneni (Programmer), Mark Woodward (Senior Statistician).• Kidney Disease Improving Global Outcomes (KDIGO) Controversies Conference on Prognosis and Optimal Management of Patients with Advanced CKD: Kai-Uwe Eckardt (Conference Co-Chair), Brenda R. Hemmelgarn (Conference Co-Chair), David C. Wheeler (KDIGO Co-Chair), Wolfgang C. Winkelmayer (KDIGO Co-Chair), John Davis (CEO), Danielle Green (Managing Director), Michael Cheung (Chief Scientific Officer), Tanya Green (Communications Director), Melissa McMahan (Programs Director).

Simple Summary The pain caused by surgical procedures performed routinely for managing livestock husbandry is recognised as a significant animal welfare issue for food security. In recent years, there has been progress encouraging the uptake of pain relief in extensively managed livestock operations, with research and development offering options for the practical delivery of anaesthetics and analgesics during these procedures. In Australia, topical anaesthetic and buccal meloxicam treatments are now commercially available for use during routine surgical husbandry procedures of lambs and calves. A study to assess the effect of these treatments on weight gain and behavioural variables following concurrent surgical castration and amputation dehorning in beef calves is reported. Results showed that a combination of topical anaesthetic and buccal meloxicam appeared to reduce pain following castration and dehorning, with improved weight gain and increased lying activity in the first few days following the procedures. In addition, some individual behaviours expressed by the calves on the day of treatment suggested pain was relieved by topical anaesthetic and buccal meloxicam, although further clarification of this observation is required. These findings demonstrate that provision of topical anaesthetic and buccal meloxicam to beef calves undergoing surgical castration and amputation dehorning can result in improved animal welfare and production. Abstract The use of pain relief during castration and dehorning of calves on commercial beef operations can be limited by constraints associated with the delivery of analgesic agents. As topical anaesthetic (TA) and buccal meloxicam (MEL) are now available in Australia, offering practical analgesic treatments for concurrent castration and dehorning of beef calves, a study was conducted to determine their efficacy in providing pain relief when applied separately or in combination. Weaner calves were randomly allocated to; (1) no castration and dehorning/positive control (CONP); (2) castration and dehorning/negative control (CONN); (3) castration and dehorning with buccal meloxicam (BM); (4) castration and dehorning with topical anaesthetic (TA); and (5) castration and dehorning with buccal meloxicam and topical anaesthetic (BMTA). Weight gain, paddock utilisation, lying activity and individual behaviours following treatment were measured. CONP and BMTA calves had significantly greater weight gain than CONN calves (p < 0.001). CONN calves spent less time lying compared to BMTA calves on all days (p < 0.001). All dehorned and castrated calves spent more time walking (p = 0.024) and less time eating (p < 0.001) compared to CONP calves. There was a trend for CONP calves to spend the most time standing and CONN calves to spend the least time standing (p = 0.059). There were also trends for the frequency of head turns to be lowest in CONP and BMTA calves (p = 0.098) and tail flicks to be highest in CONN and BM calves (p = 0.061). The findings of this study suggest that TA and MEL can potentially improve welfare and production of calves following surgical castration and amputation dehorning.

The capacity of a commercially available gamma interferon (IFNγ) assay to detect infected sheep early in the pathogenesis of Johne's disease enables the removal of such animals from the flock before bacterial shedding and pasture contamination. However, nonspecific IFNγ responses in the assay have meant that to achieve high-test specificity, there has been a reduction in sensitivity. Although the optimal conditions for the use of the assay in cattle have been well documented, there have been few studies optimizing the assay for use in sheep. The current study details the effect of anticoagulant, duration of incubation, cell concentration, blood storage temperature, time of stimulation of cells with antigen relative to time of sample collection, and temperatures during transit on IFNγ synthesis. Maximal IFNγ synthesis occurred with incubation periods of 48 hr in blood collected into heparinized tubes. Decreasing the leukocyte population by diluting the total peripheral blood leukocyte concentration was associated with a decreasing IFNγ response. Conversely, concentrating the peripheral blood concentration 2-fold resulted in an increase in the IFNγ production. In field studies, immediate incubation of blood samples with antigen at 37°C resulted in larger IFNγ responses; however, significantly lower IFNγ values were obtained if the samples were transported at ambient temperature. The results of this study indicate that optimization of the IFNγ assay may enable increased synthesis of IFNγ during the stimulation phase of the assay and that future work may determine whether this translates to increased sensitivity of the assay in detecting early infections in sheep.

An in vitro bovine mammosphere model was characterized for use in lactational biology studies using a functional genomics approach. Primary bovine mammary epithelial cells cultured on a basement membrane, Matrigel, formed three-dimensional alveoli-like structures or mammospheres. Gene expression profiling during mammosphere formation by high-density microarray analysis indicated that mammospheres underwent similar molecular and cellular processes to developing alveoli in the mammary gland. Gene expression profiles indicated that genes involved in milk protein and fat biosynthesis were expressed, however, lactose biosynthesis may have been compromised. Investigation of factors influencing mammosphere formation revealed that extracellular matrix (ECM) was responsible for the initiation of this process and that prolactin (Prl) was necessary for high levels of milk protein expression. CSN3 (encoding kappa-casein) was the most highly expressed casein gene, followed by CSN1S1 (encoding alphaS1-casein) and CSN2 (encoding beta-casein). Eighteen Prl-responsive genes were identified, including CSN1S1, SOCS2 and CSN2, however, expression of CSN3 was not significantly increased by Prl and CSN1S2 was not expressed at detectable levels in mammospheres. A number of novel Prl responsive genes were identified, including ECM components and genes involved in differentiation and apoptosis. This mammosphere model is a useful model system for functional genomics studies of certain aspects of dairy cattle lactation.

Our objectives were to document the biosecurity practices implemented at agricultural shows in Australia and to measure the potential for pigs to consume swill at shows. An observational study was conducted at 6 agricultural shows in 2006 to identify the potential for pigs to consume swill. In addition, a questionnaire on biosecurity practices was distributed to administrative personnel responsible for 64 pig exhibits at 46 agricultural shows in Australia in 2005. A total of 153 feed exposure events were recorded during the 22-day observation period, of which 48 (31.3%) were identified as swill. Health status declarations for incoming pigs were required by 11.7% of exhibits. Exhibitors were solely responsible for monitoring the health of the pigs while at the show in 17 (28.3%) exhibits. Where agricultural show staff were responsible for health monitoring, only 2 of 60 respondents stated their staff had training in disease recognition. In 49 (83.1%) exhibits, pig manure was disposed outside of the showground. Our results demonstrate that current biosecurity practices at pig exhibits at agricultural shows in Australia may allow the introduction and dissemination of exotic diseases, particularly FMD.

The immunological function of the metatherian mammary gland plays a crucial part in neonatal survival of the marsupial young. Marsupial pouch young do not develop adult like immune responses until just prior to leaving the pouch. The immune components of the maternal milk secretions are important during this vulnerable early post-partum period. In addition, infection of the mammary gland has not been recognized in metatherians, despite the ready availability of pathogens in the pouch. Regardless of which, little is known about the immunobiology of the mammary gland and the immune responses of mammary epithelial cells in metatherians. In this study, a molecular approach was utilized to examine the response of tammar ( Macropus eugenii ) mammary epithelial cells to Escherichia coli derived lipopolysaccharide (LPS) and Staphylococcus aureus derived lipoteichoic acid (LTA). Using custom-made cDNA microarrays, candidate genes were identified in the transciptome, which were involved in antigen presentation, inflammation, cell growth and proliferation, cellular damage and apoptosis. Quantification of mRNA expression of several of these candidate genes, along with seven other genes (TLR4, CD14, TNF-α, cathelicidin, PRDX1, IL-5 and ABCG2) associated with innate immunity in LPS and LTA challenged mammary epithelial cells and leukocytes, was assessed for up to 24 h. Differences in genes associated with cellular damage and pro-inflammatory cytokine production were seen between stimulated mammary epithelial cells and leukocytes. LTA challenge tended to result in lower level induction of pro-inflammatory cytokines, increased PRDX1 mRNA levels, suggesting increased oxidative stress, and increased CD14 expression, but in a non-TLR4-dependent manner. The use of functional genomic tools in the tammar identified differences in the response of tammar mammary epithelial cells (MEC) and leukocytes to challenge with LPS and LTA, and validates the utility of the approach. The results of this study are consistent with a model in which tammar mammary epithelial cells have the capacity to elicit a complex and robust immune response to pathogens.

A marker-assisted introgression (MAI) experiment was conducted to transfer trypanotolerance quantitative trait loci (QTL) from a donor mouse strain, C57BL/6, into a recipient mouse strain, A/J. The objective was to assess the effect of three previously identified chromosomal regions on mouse chromosomes 1 (MMU1), 5 (MMU5) and 17 (MMU17) in different genetic backgrounds on the survival pattern following infection with Trypanosoma congolense. An exploratory data analysis revealed a biphasic pattern of time to death, with highly distinct early and late mortality phases. In this paper, we present survival analysis methods that account for the biphasic mortality pattern and results of reanalyzing the data from the MAI experiment. The analysis with a Weibull mixture model confirmed the biphasic pattern of time to death. Mortality phase, an unobserved variable, appears to be an important factor influencing survival time and is modeled as a binary outcome variable using logistic regression analysis. Accounting for this biphasic pattern in the analysis reveals that a previously observed sex effect on average survival is rather an effect on proportion of mice in the two mortality phases. The C57BL/6 (donor) QTL alleles on MMU1 and MMU17 act dominantly in the late mortality phase while the A/J (recipient) QTL allele on MMU17 acts dominantly in the early mortality phase. From this study, we found clear evidence for a biphasic survival pattern and provided models for its analysis. These models can also be used when studying defense mechanisms against other pathogens. Finally, these approaches provide further information on the nature of gene actions.

The lowest dose of frozen-thawed boar sperm used for deep uterine artificial insemination (DUI) of sows has been 100x10(6). A three stage field study was performed to establish to what level the dose of frozen-thawed sperm used for DUI could be reduced without adversely affecting the fertility of the sow. In stage 1, 15 sows were inseminated twice with 1000x10(6) fresh or frozen-thawed sperm at 24 and 36 h post-detection of oestrus. In stage 2, 262 sows were inseminated with 62.5, 250 or 1000x10(6) fresh or frozen-thawed sperm at 24, 36, or 24 and 36 h after detection of oestrus. Stage 3 involved post mortem investigation of the uterine lining to assess damage caused by insertion of the insemination catheter. All sows inseminated in stage 1 of the study farrowed. In stage 2, the non-return (NRR) and farrowing rates of each group were compared to a control double cervical insemination of 3250x10(6) fresh sperm. As few as 62.5x10(6) fresh sperm could be deposited at a single insemination without reduction in NRR or farrowing rates compared with the control group. A double DUI with 250x10(6) frozen-thawed sperm was required before fertility was equivalent to the controls. Investigation of the uterine lining after insertion of the DUI catheter revealed evidence of bleeding, warranting further investigation of the viability of widespread use of the Firflex catheter, despite the promising fertility achieved here with low doses of spermatozoa.

This paper reports on the use of plastic mats by rams housed in pens with wire mesh floors and the motivational consequences of short-term removal of these mats. Six rams were monitored for 5 days before and after the introduction of mats. The mats were then removed for 24 h. There was a peak in the lying rate of rams on the first day the mats were returned. This post-inhibitory rebound may reflect a rise in internal motivation to lie down during the period of prevention. Behaviours that exhibit this pattern of motivation are generally considered functional, and it has been argued that their prevention may compromise welfare. Therefore this report supports the use of appropriately designed plastic mats in housed rams that would otherwise be required to lie on wire mesh.

To retrospectively compare the frequency of administration and cumulative dose of gadolinium-based contrast agent in dialysis-dependent patients who did and those who did not develop nephrogenic systemic fibrosis.The ethics committees granted exempt status for this study and also waived the need for informed consent. A retrospective analysis was performed of all adult patients undergoing dialysis in the west of Scotland between January 1, 2000, and July 1, 2006. Diagnoses of nephrogenic systemic fibrosis, episodes of gadolinium-enhanced magnetic resonance (MR) imaging, and cumulative doses of gadolinium-based contrast agent were recorded. Outcomes were analyzed by means of parametric and nonparametric testing.Fourteen of 1826 patients had a diagnosis of nephrogenic systemic fibrosis. Mortality was similar for affected and nonaffected patients. Thirteen (93%) of 14 patients with nephrogenic systemic fibrosis had undergone gadolinium-enhanced MR imaging compared with 408 (22.5%) of 1812 nonaffected patients (P.001). Patients with nephrogenic systemic fibrosis received a higher median cumulative dose of gadodiamide (0.39 vs 0.23 mmol per kilogram of body weight, P=.008) and underwent more gadolinium-enhanced MR imaging than their nonaffected gadolinium-exposed counterparts.The data support a positive association between gadolinium-based contrast agent administration and development of nephrogenic systemic fibrosis in the established renal failure population; in addition, there is a positive association between cumulative dose of gadodiamide used and dosing events.

Motility characteristics (assessed subjectively and with computer-assisted semen analysis) and membrane status (after staining with chlortetracycline) of washed and non-washed frozen-thawed ram spermatozoa were evaluated after incubation in buffer and buffer containing autologous whole seminal plasma or one of its two fractions: the pellet of membrane vesicles obtained by ultracentrifugation (and used at three times normal protein concentration) or the vesicle-free supernatant fraction. Whole seminal plasma and supernatant, but not membrane vesicles, improved the motility characteristics of spermatozoa after 3 and 6 h of post-thaw incubation compared with the control buffer. Resuspension and incubation with whole seminal plasma, supernatant or membrane vesicles lowered the proportion of acrosome-reacted frozen-thawed spermatozoa compared with the control buffer. Unwashed frozen-thawed semen from three rams, incubated with autologous whole seminal plasma or its fractions and inseminated using cervical or intrauterine artificial insemination, had no effect on pregnancy rates of ewes in synchronized oestrus. However, fertility was higher after laparoscopic than cervical insemination (44.9 vs 12.3%, p < 0.001). In conclusion, resuspension and incubation of frozen-thawed ram spermatozoa in autologous whole seminal plasma or its vesicle-free supernatant fraction improved their motility characteristics and, with membrane vesicles, membrane status, but these benefits were not reflected in improved fertility after cervical or intrauterine insemination.

The effect of gonadotropin releasing hormone (GnRH) treatment on the time of ovulation and the occurrence of follicular dominance during the non-breeding and breeding seasons (experiment 1), and on fertility after artificial insemination (AI) in the non-breeding season (experiment 2), was examined in Merino ewes. Oestrus was synchronized in 40 nulliparous ewes (experiment 1; n = 20, in the non-breeding and breeding seasons) and in 79 multiparous ewes (experiment 2) using intravaginal sponges and pregnant mare serum gonadotropin. Thirty six hours after sponge removal (SR), half the ewes were injected (i.m.) with 40 microg of synthetic GnRH and the remainder used as controls. GnRH improved the synchrony of ovulation compared with the controls in the breeding (SD = 2.8 vs 5.7 days, p = 0.04) but not the non-breeding season (SD = 3.8 vs 4.4 days, p = 0.69), with ewes ovulating from 42 to 54 h (mean 50.4 +/- 4.08 h) and 42-60 h (mean 54.4 +/- 5.47 h) after SR for GnRH and control, respectively. For both treated and control ewes, ovulation occurred earlier in the non-breeding than the breeding season (50.1 vs 54.6 h; p = 0.002). GnRH had no effect on follicular dominance, as assessed by divergence (D: the time the ovulatory follicle exceeded the average size of the other non-ovulating follicles) or on the interval from D to ovulation (IDO). However, follicular dynamics differed between seasons. The mean follicle diameter increased at a faster rate up to 36 h after SR in the non-breeding compared with the breeding season and then rapidly declined, compared with a later peak (42 h after SR) in mean follicular size during the breeding season. IDO was shorter in the non-breeding than in the breeding season (26.7 +/- 4.30 h vs 39.6 +/- 4.53 h; p = 0.05). In experiment 2, ewes (n = 38 GnRH-treated, n = 40 controls) were inseminated in the uterus by laparoscopy 42 h or 48 h after SR with frozen-thawed sperm. The fertility of ewes treated with GnRH (nine of 39, 23%) was not different to the controls (eight of 38, 21%; p = 0.01). In conclusion the application of GnRH improved synchronization of ovulation but did not improve fertility rates after AI.