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1.  Irish Veterinary Journal reviewer acknowledgement 2013 
Irish Veterinary Journal  2014;67(1):3.
Contributing reviewers
The Irish Veterinary Journal editorial team would like to thank the following colleagues who contributed to peer review for the journal in 2013.
doi:10.1186/2046-0481-67-3
PMCID: PMC3923565  PMID: 24524550
2.  The association between ANKH promoter polymorphism and chondrocalcinosis is independent of age and osteoarthritis: results of a case–control study 
Introduction
Chondrocalcinosis (CC) most commonly results from calcium pyrophosphate crystal deposition (CPPD). The objective of this study is to examine the association between candidate single-nucleotide polymorphisms (SNPs) and radiographic CC.
Methods
SNPs in ankylosis human (ANKH), high ferritin (HFE), tissue non-specific alkaline phosphatase (TNAP), ecto-neucleotide pyrophosphatase 1 (ENPP1), and transferrin (TE) genes were genotyped in participants of the Genetics of Osteoarthritis and Lifestyle (GOAL) and Nottingham Osteoarthritis Case-Control studies. Adjusted genotype odds ratio (aORGENOTYPE), the OR for association between one additional minor allele and CC, was calculated and adjusted for age, gender, body mass index (BMI), and osteoarthritis (OA) by using binary logistic regression. Statistical significance was set at P ≤0.003 after Bonferroni correction for multiple tests.
Results
The -4bpG > A polymorphism in the 5′ untranslated region (5′ UTR) of ANKH associated with CC after Bonferroni correction. This was independent of age, gender, OA, and BMI; aORGENOTYPE (95% confidence interval, or CI) was 1.39 (1.14-1.69) (P = 0.001). rs3045 and rs875525, two other SNPs in ANKH, associated with CC; aORGENOTYPE (95% CI) values were 1.31 (1.09-1.58) (P = 0.005) and 1.18 (1.03-1.35) (P = 0.015), respectively; however, this was non-significant after Bonferroni correction.
Conclusions
This study validates the association between a functional polymorphism in the 5′ UTR of ANKH and CC and shows for the first time that this is independent of age and OA – the two key risk factors for CC. It shows that other SNPs in ANKH may also associate with CC. This supports the role of extracellular inorganic pyrophosphate in the pathogenesis of CC. The findings of this hospital-based study require replication in a community-based population.
doi:10.1186/ar4453
PMCID: PMC3978851  PMID: 24467728
3.  Herd health status and management practices on 16 Irish suckler beef farms 
Irish Veterinary Journal  2013;66(1):21.
Background
There have been few studies published internationally which document herd health management practices in suckler beef herds and no published Irish studies. The study objective was to document herd health status and management practices on sixteen Irish suckler beef herds over a two year period (2009–2010). The farms used in the study were part of the Teagasc BETTER farm beef programme. The mean (s.d.) herd size, stocking rate and farm size was 68 cows (27.6), 2.0 LU/ha (0.3) and 64.3 (21.6) adjusted hectares, respectively. Two questionnaires were designed; 1) a farmer questionnaire to collect information on farm background and current herd health control practices and 2) a veterinary questionnaire to collect information on the extent of animal health advice given by veterinarians to their clients and identification of any on-farm herd health issues.
Results
Dystocia, calf pneumonia, and calf diarrhoea, in that order, were identified as the primary herd health issues in these Irish suckler beef herds. In addition, substantial deficiencies in biosecurity practices were also identified on these farms.
Conclusions
The findings of this study may serve as the focus for future research in animal health management practices in Irish suckler beef herds.
doi:10.1186/2046-0481-66-21
PMCID: PMC3903451  PMID: 24195997
Herd health; Beef suckler; Management practices
4.  Performance of Global Assessments of Hip, Knee, and Back Symptom Change 
Clinical rheumatology  2010;30(3):331-338.
Objective
To compare patients’ global assessments of change in knee, hip, and back symptoms with actual changes over time in pain, function, and radiographic severity.
Methods
Participants (n=894, 80% female, mean age=66 years) completed two assessments (mean of 4 years apart) as part of a study on the genetics of generalized osteoarthritis. At both assessments, participants completed the Western Ontario and McMaster Universities OA Index (WOMAC), and radiographic severity was assessed for knees, hips, and low back. At the second assessment, participants described changes in knee, hip, and low back symptoms as Worse, Better, Same, or Never Had Symptoms. Analysis of covariance models examined mean changes in WOMAC scores and radiographic severity according to categories of the global assessment measures. Statistical significance was examined for linear trend.
Results
Mean WOMAC total, pain, and function scores decreased (indicating improvement) among participants who indicated joint symptoms were Better; showed little change among those who reported symptoms were the Same/Never Had Symptoms; and increased among those who reported symptoms were Worse. For all analyses except the comparison of WOMAC pain change according to global assessment of low back symptom change, there was a statistically significant linear trend (p<0.05). Patterns were similar for changes in radiographic severity, but the tests of linear trend were not statistically significant.
Conclusion
Results support the concordance of these global assessments of joint symptom change with actual changes in self-reported symptoms. These global assessments may be useful for assessing change over time when baseline data are unavailable.
doi:10.1007/s10067-010-1536-x
PMCID: PMC3731381  PMID: 20683742
Osteoarthritis; Knee; Hip; Back; Pain; Function; Psychometrics
5.  Bulk milk ELISA and the diagnosis of parasite infections in dairy herds: a review 
Irish Veterinary Journal  2013;66(1):14.
The bulk milk enzyme-linked immune sorbent assay (ELISA) is a rapid and inexpensive method of assessing herd exposure to pathogens that is increasingly being used for the diagnosis of parasite infections in dairy herds. In this paper, with the dairy herd health veterinarian in mind, we review the principles of the assay and the recent literature on the potential role of bulk milk ELISA for the diagnosis of ostertagiosis, fasciolosis, parasitic bronchitis due to cattle lung worm and neosporosis. It is generally accepted that assay results reflect exposure to the parasite rather than the presence of active infection. Bulk milk ELISA can be a useful tool for the veterinary practitioner as a component of a herd health monitoring programme or in the context of a herd health investigation. It can also play a role in regional or national surveillance programmes. However, the results need to be interpreted within the context of the herd-specific health management, the milk production pattern and the parasite life cycle.
doi:10.1186/2046-0481-66-14
PMCID: PMC3733751  PMID: 23883526
Bulk milk ELISA; Dairy herds; Parasite infections; Ostertagia; Fasciola; Dictyocaulus; Neospora
6.  Individual patient data meta-analysis of trials investigating the effectiveness of intra-articular glucocorticoid injections in patients with knee or hip osteoarthritis: an OA Trial Bank protocol for a systematic review 
Systematic Reviews  2013;2:54.
Background
Based on small to moderate effect sizes for the wide range of symptomatic treatments in osteoarthritis (OA), and on the heterogeneity of OA patients, treatment guidelines for OA have stressed the need for research on clinical predictors of response to different treatments. A meta-analysis to quantify the effect modified by the predictors using individual patient data (IPD) is suggested. The initiative to collect and analyze IPD in OA research is commenced by the OA Trial Bank. The study aims are therefore: to evaluate the efficacy of intra-articular glucocorticoids for knee or hip OA in specific subgroups of patients with severe pain and (mild) inflammatory signs, over both short-term and long-term follow-up, using IPD from existing studies; to reach consensus on the rules for cooperation in a consortium; and to develop and explore the methodological issues of meta-analysis with individual OA patient data.
Methods/Design
For the current IPD analysis we will collect and synthesize IPD from randomized trials studying the effect of intra-articular glucocorticoid injections in patients with hip or knee OA. Subgroup analyses will be performed for the primary outcome of pain at both short-term and long-term follow-up, in the subgroups of patients with and without severe pain and with and without inflammatory signs.
Discussion
This study protocol includes the first study of the OA Trial Bank, an international collaboration that initiates meta-analyses on predefined subgroups of OA patients from existing literature. This approach ensures a widely supported initiative and is therefore likely to be successful in data collection of existing trials. The collaboration developed (that is, the OA Trial Bank) may also lead to future IPD analyses on subgroups of patients with several intervention strategies applied in OA patients.
doi:10.1186/2046-4053-2-54
PMCID: PMC3707758  PMID: 23830482
Osteoarthritis; Individual patient data; Corticosteroid injection
7.  A Role for PACE4 in Osteoarthritis Pain: Evidence from Human Genetic Association and Null Mutant Phenotype 
Annals of the rheumatic diseases  2012;71(6):1042-1048.
Objectives
To assess if genetic variation in the PACE4 gene, PCSK6, influences the risk for symptomatic knee OA.
Methods
Ten PCSK6 single nucleotide polymorphisms (SNP) were tested for association in a discovery cohort of radiographic knee OA (n= 156 asymptomatic and 600 symptomatic cases). Meta-analysis of the minor allele at rs900414 was performed in three additional independent cohorts (total n=674 asymptomatic and 2068 symptomatic). Pcsk6 knockout (KO) mice and wildtype C57BL/6 mice were compared in a battery of algesiometric assays, including hypersensitivity in response to intraplantar substance P; pain behaviours in response to intrathecal substance P; and pain behaviour in the abdominal constriction test.
Results
In the discovery cohort of radiographic knee OA, an intronic SNP at rs900414 was significantly associated with symptomatic OA. Replication in three additional cohorts confirmed that the minor allele at rs900414 was consistently increased among asymptomatic compared to symptomatic radiographic knee OA cases in all four cohorts. A fixed-effects meta-analysis yielded an odds ratio =1.35 (95% CI 1.17, 1.56; p-value 4.3×10−5 and no significant between-study heterogeneity). Studies in mice revealed that Pcsk6 knockout (KO) mice were significantly protected against pain in a battery of algesiometric assays.
Conclusions
These results suggest that a variant in PCSK6 is strongly associated with protection against pain in knee OA, offering some insight as to why in the presence of the same structural damage, some individuals develop chronic pain and others are protected. Studies in Pcsk6 null mutant mice further implicate PACE4 in pain.
doi:10.1136/annrheumdis-2011-200300
PMCID: PMC3603144  PMID: 22440827
Knee osteoarthritis; pain; PACE4; genetic association; SNP
8.  Absence of association of asporin polymorphisms and osteoarthritis susceptibility in US Caucasians 
Objective
An association between osteoarthritis (OA) and functional polymorphisms in the aspartic acid (D) repeat of the asporin (ASPN) gene was reported in Japanese and Han Chinese populations. The aim of this study was to assess the association of variants in the ASPN gene with the presence of radiographic hand and/or knee OA in a US Caucasian population.
Methods
Ten SNPs within the ASPN gene were genotyped in 775 affected siblings with radiographically confirmed hand or knee OA, and the allelic, genotypic and haplotypic association results were examined.
Results
One variant (SNP RS7033979) showed nominal evidence of association with both hand OA (P=0.042) and knee OA (P=0.032). Four additional SNPs showed nominal evidence of association with knee OA only. These associations were only observed with genotypic tests; the corresponding allelic and haplotype tests did not corroborate the single-point association results.
Conclusion
These data suggest that polymorphisms within ASPN are not a major influence in susceptibility to hand or knee OA in US Caucasians.
doi:10.1016/j.joca.2008.03.007
PMCID: PMC3664276  PMID: 18434216
9.  Meta-analysis of genome-wide association studies confirms a susceptibility locus for knee osteoarthritis on chromosome 7q22 
Evangelou, Evangelos | Valdes, Ana M. | Kerkhof, Hanneke J.M | Styrkarsdottir, Unnur | Zhu, YanYan | Meulenbelt, Ingrid | Lories, Rik J. | Karassa, Fotini B. | Tylzanowski, Przemko | Bos, Steffan D. | Akune, Toru | Arden, Nigel K. | Carr, Andrew | Chapman, Kay | Cupples, L. Adrienne | Dai, Jin | Deloukas, Panos | Doherty, Michael | Doherty, Sally | Engstrom, Gunnar | Gonzalez, Antonio | Halldorsson, Bjarni V. | Hammond, Christina L. | Hart, Deborah J. | Helgadottir, Hafdis | Hofman, Albert | Ikegawa, Shiro | Ingvarsson, Thorvaldur | Jiang, Qing | Jonsson, Helgi | Kaprio, Jaakko | Kawaguchi, Hiroshi | Kisand, Kalle | Kloppenburg, Margreet | Kujala, Urho M. | Lohmander, L. Stefan | Loughlin, John | Luyten, Frank P. | Mabuchi, Akihiko | McCaskie, Andrew | Nakajima, Masahiro | Nilsson, Peter M. | Nishida, Nao | Ollier, William E.R. | Panoutsopoulou, Kalliope | van de Putte, Tom | Ralston, Stuart H. | Rivadeneira, Fernado | Saarela, Janna | Schulte-Merker, Stefan | Slagboom, P. Eline | Sudo, Akihiro | Tamm, Agu | Tamm, Ann | Thorleifsson, Gudmar | Thorsteinsdottir, Unnur | Tsezou, Aspasia | Wallis, Gillian A. | Wilkinson, J. Mark | Yoshimura, Noriko | Zeggini, Eleftheria | Zhai, Guangju | Zhang, Feng | Jonsdottir, Ingileif | Uitterlinden, Andre G. | Felson, David T | van Meurs, Joyce B. | Stefansson, Kari | Ioannidis, John P.A. | Spector, Timothy D.
Annals of the rheumatic diseases  2010;70(2):349-355.
Osteoarthritis (OA) is the most prevalent form of arthritis and accounts for substantial morbidity and disability, particularly in the elderly. It is characterized by changes in joint structure including degeneration of the articular cartilage and its etiology is multifactorial with a strong postulated genetic component. We performed a meta-analysis of four genome-wide association (GWA) studies of 2,371 knee OA cases and 35,909 controls in Caucasian populations. Replication of the top hits was attempted with data from additional ten replication datasets. With a cumulative sample size of 6,709 cases and 44,439 controls, we identified one genome-wide significant locus on chromosome 7q22 for knee OA (rs4730250, p-value=9.2×10−9), thereby confirming its role as a susceptibility locus for OA. The associated signal is located within a large (500kb) linkage disequilibrium (LD) block that contains six genes; PRKAR2B (protein kinase, cAMP-dependent, regulatory, type II, beta), HPB1 (HMG-box transcription factor 1), COG5 (component of oligomeric golgi complex 5), GPR22 (G protein-coupled receptor 22), DUS4L (dihydrouridine synthase 4-like), and BCAP29 (the B-cell receptor-associated protein 29). Gene expression analyses of the (six) genes in primary cells derived from different joint tissues confirmed expression of all the genes in the joint environment.
doi:10.1136/ard.2010.132787
PMCID: PMC3615180  PMID: 21068099
10.  Will the EU Clinical Trials Regulation Support the Innovative Industry in Bringing New Medicines Faster to Patients? 
Pharmaceutical Medicine  2013;27:75-82.
A perspective from the innovative industry is provided in this article about the long awaited legal proposal for a Clinical Trial Regulation (“Proposal”), adopted in July 2012. With this Proposal, the European Commission reacted to a call by all stakeholders for more harmonization and streamlining of the provisions for conducting clinical trials in the EU. Discrepant approaches between Member States, a failure to respect legal timelines, and a lack of formal coordination mechanisms within and between Member States have resulted in an increased workload for the industry and contributed to a decline in Europe’s attractiveness as a place to carry out research and development. The Proposal introduces a concept whereby the sponsor makes a single submission of the clinical trial application dossier to an EU portal, which is followed by a single assessment based on cooperation between Member States. A possibility for the sponsor to choose a ‘reporting Member State’ to take the lead on key aspects of the assessment is expected to support excellence building and work sharing of Competent Authorities in the EU. The Proposal respects the fact that certain aspects need to be reviewed nationally. The new process aims to lead to a single decision per clinical trial per concerned Member State. The rules are built on the principle of strict adherence to timelines for authorization. The timelines are ambitious but at the same time competitive, as the process builds in mechanisms that strengthen compliance. The rules have been designed to encourage sponsors to file complete submission packages, since any substantial modification to a trial would lead to delays in its commencement. Sponsors need to streamline their internal processes accordingly. In the end, streamlining is an effort that needs to be accepted by all parties involved. The Proposal does not detail how Member States organize the involvement of different bodies, such as Competent Authorities and Ethics Committees, because according to the EU Treaty, the EU cannot legislate on aspects falling into pure Member State competence. The Proposal, however, establishes the assessment objectives on the basis of Good Clinical Practices set by the International Conference on Harmonisation (ICH) and the Declaration of Helsinki by the World Medical Association. As such, the new legislation is likely to have implications on Member States’ internal organization. In addition, Ethics Committees in Europe would benefit from an EU platform for best practice exchange—a concept that would need to be requested by the Council and the European Parliament through the legislative process. A single decision system for the entire EU per clinical trial has been discussed as an option, but such an approach was difficult to achieve while respecting national competencies. In this situation, the Proposal represents an acceptable compromise, provided its proposed mechanisms, processes, and timelines are retained upon implementation. As the Proposal is now on the table for discussion by the 27 Member States’ governments and by the European Parliament, co-legislators and stakeholders should be aware that any dilution of these provisions would be detrimental to the objective to ensure patient access and make the conditions for clinical research in Europe attractive and fit for the future.
doi:10.1007/s40290-013-0012-8
PMCID: PMC3622747  PMID: 23585715
11.  Hydroxychloroquine effectiveness in reducing symptoms of hand osteoarthritis (HERO): study protocol for a randomized controlled trial 
Trials  2013;14:64.
Background
Osteoarthritis (OA) is the most common type of arthritis, causing significant joint pain and disability. It is already a major cause of healthcare expenditure and its incidence will further increase with the ageing population. Current treatments for OA have major limitations and new analgesic treatments are needed. Synovitis is prevalent in OA and is associated with pain. Hydroxychloroquine is used in routine practice for treating synovitis in inflammatory arthritides, such as rheumatoid arthritis. We propose that treating patients with symptomatic hand OA with hydroxychloroquine will be a practical and safe treatment to reduce synovitis and pain.
Methods/design
HERO is an investigator-initiated, multicentre, randomized, double-blind, placebo-controlled trial. A total of 252 subjects with symptomatic hand OA will be recruited across primary and secondary care sites in the UK and randomized on a 1:1 basis to active treatment or placebo for 12 months. Daily medication dose will range from 200 to 400 mg according to ideal body weight. The primary endpoint is change in average hand pain during the previous two weeks (measured on a numerical rating scale (NRS)) between baseline and six months. Secondary endpoints include other self-reported pain, function and quality-of-life measures and radiographic structural change at 12 months. A health economics analysis will also be performed. An ultrasound substudy will be conducted to examine baseline levels of synovitis. Linear and logistic regression will be used to compare changes between groups using univariable and multivariable modelling analyses. All analyses will be conducted on an intention-to-treat basis.
Discussion
The HERO trial is designed to examine whether hydroxychloroquine is an effective analgesic treatment for OA and whether it provides any long-term structural benefit. The ultrasound substudy will address whether baseline synovitis is a predictor of therapeutic response. This will potentially provide a new treatment for OA, which could be of particular use in the primary care setting.
Trial registration
ISRCTN91859104.
doi:10.1186/1745-6215-14-64
PMCID: PMC3716636  PMID: 23452375
Double-blind; Hand osteoarthritis; Hydroxychloroquine; Placebo-controlled; Randomized
12.  Chondrocalcinosis is common in the absence of knee involvement 
Arthritis Research & Therapy  2012;14(5):R205.
Introduction
We aimed to describe the distribution of radiographic chondrocalcinosis (CC) and to examine whether metacarpophalangeal joint (MCPJ) calcification and CC at other joints occurs in the absence of knee involvement.
Methods
This was a cross-sectional study embedded in the Genetics of Osteoarthritis and Lifestyle study (GOAL). All participants (n = 3,170) had radiographs of the knees, hands, and pelvis. These were scored for radiographic changes of osteoarthritis (OA), for CC at knees, hips, symphysis pubis, and wrists, and for MCPJ calcification. The prevalence of MCPJ calcification and CC overall, at each joint, and in the presence or absence of knee involvement, was calculated.
Results
The knee was the commonest site of CC, followed by wrists, hips, and symphysis pubis. CC was more likely to be bilateral at knees and wrists but unilateral at hips. MCPJ calcification was usually bilateral, and less common than CC at knees, hips, wrists, and symphysis pubis. Unlike that previously reported, CC commonly occurred without any knee involvement; 44.4% of wrist CC, 45.9% of hip CC, 45.5% of symphysis pubis CC, and 31.3% of MCPJ calcification occurred in patients without knee CC. Those with meniscal or hyaline articular cartilage CC had comparable ages (P = 0.21), and neither preferentially associated with fibrocartilage CC at distant joints.
Conclusions
CC visualized on a plain radiograph commonly occurs at other joints in the absence of radiographic knee CC. Therefore, knee radiographs alone are an insufficient screening test for CC. This has significant implications for clinical practice, for epidemiologic and genetic studies of CC, and for the definition of OA patients with coexistent crystal deposition.
doi:10.1186/ar4043
PMCID: PMC3580517  PMID: 23036436
13.  Morphological Differences between Chinese and Caucasian Female Hips: Could they account for the ethnic difference in hip osteoarthritis? 
Arthritis and rheumatism  2011;63(10):2992-2999.
Background
Hip osteoarthritis (OA) is a common disabling disease, which has a much higher prevalence in Caucasians than Asians. The reasons for this ethnic difference in prevalence are unknown. Hip OA often is thought to be secondary to morphologic abnormalities. If particular abnormalities predisposing to hip OA occur more frequently in Caucasians, these differences in hip shape could account for prevalence differences.
Methods
A morphometric study was performed using 400 non-osteoarthritic hips of 200 women participants from 2 studies: the Beijing OA study and the SOF study from the U.S. We focused on measures of hip dysplasia and impingement (Lateral Center Edge Angle, Impingement Angle, Acetabular Slope, Femoral Head Neck Ratio and the Cross Over Sign) and compared data from Chinese and Caucasian hips.
Results
Compared with their Chinese counterparts, Caucasian women had a lower mean impingement angle (83.6° vs. 87.0°’ p=.03) and were more likely to have center edge angles suggestive of impingement (for center edge angle >35°, 11% of Chinese vs. 23% of Caucasian hips, p = .008). On the other hand, low center edge angles suggesting dysplasia were found more often in Chinese women (for <20°, 22% of Chinese vs. 7% of Caucasian hips, p = .005).
Conclusions
In a study of elderly women without signs of OA, the morphometry of impingement and asphericity were more common in Caucasian than Chinese hips. Our findings suggest that Caucasians may be at higher risk of hip OA than Chinese because of morphologic findings that predispose them to femoro-acetabular impingement.
doi:10.1002/art.30472
PMCID: PMC3178680  PMID: 21647861
14.  Bovine viral diarrhoea virus seroprevalence and vaccination usage in dairy and beef herds in the Republic of Ireland 
Irish Veterinary Journal  2012;65(1):16.
Background
Bovine viral diarrhoea (BVD) is an infectious disease of cattle with a worldwide distribution. Herd-level prevalence varies among European Union (EU) member states, and prevalence information facilitates decision-making and monitoring of progress in control and eradication programmes. The primary objective of the present study was to address significant knowledge gaps regarding herd BVD seroprevalence (based on pooled sera) and control on Irish farms, including vaccine usage.
Methods
Preliminary validation of an indirect BVD antibody ELISA test (Svanova, Biotech AB, Uppsala, Sweden) using pooled sera was a novel and important aspect of the present study. Serum pools were constructed from serum samples of known seropositivity and pools were analysed using the same test in laboratory replicates. The output from this indirect ELISA was expressed as a percentage positivity (PP) value. Results were used to guide selection of a proposed cut-off (PCO) PP. This indirect ELISA was applied to randomly constructed within-herd serum pools, in a cross-sectional study of a stratified random sample of 1,171 Irish dairy and beef cow herds in 2009, for which vaccination status was determined by telephone survey. The herd-level prevalence of BVD in Ireland (percentage positive herds) was estimated in non-vaccinating herds, where herds were classified positive when herd pool result exceeded PCO PP. Vaccinated herds were excluded because of the potential impact of vaccination on herd classification status. Comparison of herd-level classification was conducted in a subset of 111 non-vaccinating dairy herds using the same ELISA on bulk milk tank (BMT) samples. Associations between possible risk factors (herd size (quartiles)) and herd-level prevalence were determined using chi-squared analysis.
Results
Receiver Operating Characteristics Analysis of replicate results in the preliminary validation study yielded an optimal cut-off PP (Proposed Cut-off percentage positivity - PCO PP) of 7.58%. This PCO PP gave a relative sensitivity (Se) and specificity (Sp) of 98.57% and 100% respectively, relative to the use of the ELISA on individual sera, and was chosen as the optimal cut-off since it resulted in maximization of the prevalence independent Youden’s Index.
The herd-level BVD prevalence in non-vaccinating herds was 98.7% (95% CI - 98.3-99.5%) in the cross-sectional study with no significant difference between dairy and beef herds (98.3% vs 98.8%, respectively, p = 0.595).
An agreement of 95.4% was found on Kappa analysis of herd serological classification when bulk milk and serum pool results were compared in non-vaccinating herds. 19.2 percent of farmers used BVDV vaccine; 81% of vaccinated herds were dairy. A significant association was found between seroprevalence (quartiles) and herd size (quartiles) (p < 0.01), though no association was found between herd size (quartiles) and herd-level classification based on PCO (p = 0.548).
Conclusions
The results from this study indicate that the true herd-level seroprevalence to Bovine Virus Diarrhoea (BVD) virus in Ireland is approaching 100%. The results of the present study will assist with national policy development, particularly with respect to the national BVD eradication programme which commenced recently.
doi:10.1186/2046-0481-65-16
PMCID: PMC3443026  PMID: 22849554
15.  A Genome-Wide Association Study identifies a locus on chromosome 7q22 to influence susceptibility for osteoarthritis 
Arthritis and Rheumatism  2010;62(2):499-510.
To identify genes involved in osteoarthritis (OA), the most prevalent form of joint disease, we performed a genome-wide association study (GWAS) in which we tested 500,510 Single Nucelotide Polymorphisms (SNPs) in 1341 OA cases and 3496 Dutch Caucasian controls. SNPs associated with at least two OA-phenotypes were analysed in 14,938 OA cases and approximately 39,000 controls. The C-allele of rs3815148 on chromosome 7q22 (MAF 23%, 172 kb upstream of the GPR22 gene) was consistently associated with a 1.14-fold increased risk (95%CI: 1.09–1.19) for knee- and/or hand-OA (p=8×10−8), and also with a 30% increased risk for knee-OA progression (95%CI: 1.03–1.64, p=0.03). This SNP is in almost complete linkage disequilibrium with rs3757713 (located 68 kb upstream of GPR22) which is associated with GPR22 expression levels in lymphoblast cell lines (p=4×10−12). GPR22 encodes an G-protein coupled receptor with unkown ligand (orphan receptor). Immunohistochemistry experiments showed absence of GPR22 in normal mouse articular cartilage or synovium. However, GPR22 positive chondrocytes were found in the upper layers of the articular cartilage of mouse knee joints that were challenged by in vivo papain treatment or in the presence of interleukin-1 driven inflammation. GRP22 positive chondrocyte-like cells were also found in osteophytes in instability-induced OA. In addition, GPR22 is also present in areas of the brain involved in locomotor function. Our findings reveal a novel common variant on chromosome 7q22 to influence susceptibility for prevalence and progression of OA.
doi:10.1002/art.27184
PMCID: PMC3354739  PMID: 20112360
16.  Seroprevalence of Leptospira Hardjo in the Irish suckler cattle population 
Irish Veterinary Journal  2012;65(1):8.
Background
Prior to the present study, the seroprevalence of leptospirosis in Irish suckler herds was unknown. In this study, we describe the herd and animal-level prevalence of Leptospira Hardjo infection in the Irish suckler cattle population. For the purposes of the study, the 26 counties of the Republic of Ireland were divided into 6 regions from which a representative number of herds were selected. A herd was considered eligible for sampling if it was not vaccinating against leptospirosis and if it contained ≥ 9 breeding animals of beef breed ≥ 12 months of age. In total, 288 randomly selected herds were eligible for inclusion in the seroprevalence dataset analysis. Serological testing was carried out using a commercially available monoclonal antibody-capture ELISA, (sensitivity 100%; specificity 86.67%).
Results
Herds were categorised as either “Free from Infection” or “Infected” using the epidemiological software tool, FreeCalc 2.0. Using this classification, 237 herds were “Infected” (82.29%). The South West and South East regions had the highest herd prevalence. The regional effect on herd prevalence was largely mirrored by breeding herd size. A true animal-level prevalence of 41.75% was calculated using the epidemiological software tool, TruePrev. There was a statistically significant regional trend, with true prevalence being highest in the South East (P < 0.05). The median Breeding Herd Size (BHS), when categorised into quartiles, had a statistically significant influence on individual animal true seroprevalence (P < 0.001); true seroprevalence increased with increasing BHS.
Conclusions
Leptospirosis is a widespread endemic disease in the Republic of Ireland. It is possible that economic losses due to leptospirosis in unvaccinated Irish suckler herds may be underestimated.
doi:10.1186/2046-0481-65-8
PMCID: PMC3464776  PMID: 22546216
Leptospirosis; Hardjo; Suckler; Ireland; Seroprevalence; ELISA; Herd size; Region; FreeCalc; Endemic
17.  Herd-level risk factors associated with Leptospira Hardjo seroprevalence in Beef/Suckler herds in the Republic of Ireland 
Irish Veterinary Journal  2012;65(1):6.
Background
The aim of the present study was to investigate risk factors for herd seropositivity to Leptospira Hardjo in Irish suckler herds. Herds were considered eligible for the study if they were unvaccinated and contained ≥ 9 breeding animals of beef breed which were ≥ 12 months of age. The country was divided into six regions using county boundaries. Herd and individual animal prevalence data were available from the results of a concurrent seroprevalence study. Herds were classified as either "Free from Infection" or "Infected" based on a minimum expected 40% within-herd prevalence.
Questionnaires were posted to 320 farmers chosen randomly from 6 regions, encompassing 25 counties, of the Republic of Ireland. The questionnaire was designed to obtain information about vaccination; reproductive disease; breeding herd details; the presence of recognized risk factors from previous studies; and husbandry on each farm. Data collected from 128 eligible herds were subjected to statistical analysis.
Results
Following the use of Pearson's Chi-Square Test, those variables associated with a herd being "infected" with a significance level of P < 0.2 were considered as candidates for multivariable logistic regression modelling. Breeding herd size was found to be a statistically significant risk factor after multivariable logistic regression. The odds of a herd being positive for leptospiral infection were 5.47 times higher (P = 0.032) in herds with 14 to 23 breeding animals compared with herds with ≤ 13 breeding animals, adjusting for Region, and 7.08 times higher (P = 0.033) in herds with 32.6 to 142 breeding animals.
Conclusions
Breeding herd size was identified as a significant risk factor for leptospiral infection in Irish suckler herds, which was similar to findings of previous studies of leptospirosis in dairy herds.
doi:10.1186/2046-0481-65-6
PMCID: PMC3342215  PMID: 22449264
Leptospirosis; Hardjo; Suckler; Ireland; Risk factors; Questionnaire; Herd size; Region
18.  Recommendations for standardization and phenotype definitions in genetic studies of osteoarthritis: the TREAT-OA consortium 
Objective
To address the need for standardization of osteoarthritis (OA) phenotypes by examining the effect of heterogeneity among symptomatic (SOA) and radiographic osteoarthritis (ROA) phenotypes.
Methods
Descriptions of OA phenotypes of the 28 studies involved in the TREAT-OA consortium were collected. To investigate whether different OA definitions result in different association results, we created hip OA definitions used within the consortium in the Rotterdam Study-I and tested the association of hip OA with gender, age and BMI using one-way ANOVA. For radiographic OA, we standardized the hip, knee and hand ROA definitions and calculated prevalence's of ROA before and after standardization in 9 cohort studies. This procedure could only be performed in cohort studies and standardization of SOA definitions was not feasible at this moment.
Results
In this consortium, all studies with symptomatic OA phenotypes (knee, hip and hand) used a different definition and/or assessment of OA status. For knee, hip and hand radiographic OA 5, 4 and 7 different definitions were used, respectively. Different hip OA definitions do lead to different association results. For example, we showed in the Rotterdam Study-I that hip OA defined as “at least definite JSN and one definite osteophyte” was not associated with gender (p=0.22), but defined as “at least one definite osteophyte” was significantly associated with gender (p=3×10−9). Therefore, a standardization process was undertaken for radiographic OA definitions. Before standardization a wide range of ROA prevalence's was observed in the 9 cohorts studied. After standardization the range in prevalence of knee and hip ROA was small. Standardization of SOA phenotypes was not possible due to the case-control design of the studies.
Conclusion
Phenotype definitions influence the prevalence of OA and association with clinical variables. ROA phenotypes within the TREAT-OA consortium were standardized to reduce heterogeneity and improve power in future genetics studies.
doi:10.1016/j.joca.2010.10.027
PMCID: PMC3236091  PMID: 21059398
19.  Considerations on BVD eradication for the Irish livestock industry 
Irish Veterinary Journal  2011;64(1):12.
Animal Health Ireland has produced clear guidelines for the control of Bovine Viral Diarrhoea (BVD) infection in Irish cattle herds. In the course of developing these guidelines it was clear that a framework for regional and/or national BVD control would be required to increase the uptake of BVD control at farm level and reduce the overall prevalence of the disease. This paper assessed the economic impact of BVD, epidemiological aspects of the disease to its control, models of BVD control, international experiences of BVD control programmes. The technical knowledge and test technology exists to eradicate BVD. Indeed, many countries have successfully and others are embarking on control of the disease. The identification and prompt elimination of PI cattle will form the basis of any control programme. The trade of such animals must be curtailed. Pregnant and potentially pregnant carrying PI foetuses pose a significant threat. International experience indicates systematic, well coordinated programmes have the most success, while voluntary programmes can make good initial progress but ultimately fail. The farming community must buy into any proposed programme, and without their support, failure is likely. To buy into the programme and create such a demand for BVD control, farmers must first be well informed. It is likely that stemming economic loss and improving productivity will be the primary motivator at individual farm level.
doi:10.1186/2046-0481-64-12
PMCID: PMC3199273  PMID: 21967764
20.  Large Scale Replication Study of the Association between HLA Class II/BTNL2 Variants and Osteoarthritis of the Knee in European-Descent Populations 
PLoS ONE  2011;6(8):e23371.
Osteoarthritis (OA) is the most common form of arthritis and a major cause of disability. This study evaluates the association in Caucasian populations of two single nucleotide polymorphisms (SNPs) mapping to the Human Leukocyte Antigen (HLA) region and deriving from a genome wide association scan (GWAS) of knee OA in Japanese populations. The frequencies for rs10947262 were compared in 36,408 controls and 5,749 knee OA cases from European-descent populations. rs7775228 was tested in 32,823 controls and 1,837 knee OA cases of European descent. The risk (major) allele at rs10947262 in Caucasian samples was not significantly associated with an odds ratio (OR)  = 1.07 (95%CI 0.94 -1.21; p = 0.28). For rs7775228 the meta-analysis resulted in OR = 0.94 (95%CI 0.81-1.09; p = 0.42) for the allele associated with risk in the Japanese GWAS. In Japanese individuals these two SNPs are in strong linkage disequilibrium (LD) (r2 = 0.86) with the HLA class II haplotype DRB1*1502 DQA1*0103 DQB1*0601 (frequency 8%). In Caucasian and Chinese samples, using imputed data, these SNPs appear not to be in LD with that haplotype (r2<0.07). The rs10947262 and rs7775228 variants are not associated with risk of knee OA in European descent populations and they do not appear tag the same HLA class II haplotype as they do in Japanese individuals.
doi:10.1371/journal.pone.0023371
PMCID: PMC3154440  PMID: 21853121
21.  Aspects of bovine herpesvirus-1 infection in dairy and beef herds in the Republic of Ireland 
Background
Infection with bovine herpesvirus-1 (BHV-1) causes a wide range of disease manifestations, including respiratory disease and abortion, with world-wide distribution. The primary objective of the present study was to describe aspects of BHV-1 infection and control on Irish farms, including herd-level seroprevalence (based on pooled sera) and vaccine usage.
Methods
The characteristics of a diagnostic indirect BHV-1 antibody ELISA test when used on serum pools were evaluated using laboratory replicates for use in the seroprevalence study. The output from this indirect ELISA was expressed as a percentage positivity (PP) value. A proposed cut off (PCO) PP was applied in a cross-sectional study of a stratified random sample of 1,175 Irish dairy and beef cattle herds in 2009, using serum pools, to estimate herd seroprevalence. The study was observational, based primarily on the analysis of existing samples, and only aggregated results were reported. For these reasons, ethical approval was not required. Bulk milk samples from a subset of 111 dairy herds were analysed using the same ELISA. Information regarding vaccine usage was determined in a telephone survey.
Results
A PCO PP of 7.88% was determined to give 97.1% sensitivity and 100% specificity relative to the use of the ELISA on individual sera giving maximization of the prevalence independent Youden's index, on receiver operating characteristics analysis of replicate results. The herd-level BHV-1 seroprevalence was 74.9% (95% CI - 69.9%-79.8%), with no significant difference between dairy and beef herds. 95.5% agreement in herd classification was found between bulk milk and serum pools. Only 1.8 percent of farmers used BHV-1 marker vaccine, 80% of which was live while 75% of vaccinated herds were dairy.
A significant association was found between herd size (quartiles) and seroprevalence (quartiles).
Conclusions
The results from this study indicate BHV-1 infection is endemic, although BHV-1 vaccines are rarely used, in the cattle population in Ireland.
doi:10.1186/1751-0147-53-40
PMCID: PMC3141558  PMID: 21699677
22.  Gout. Epidemiology of gout 
Gout is the most prevalent form of inflammatory arthropathy. Several studies suggest that its prevalence and incidence have risen in recent decades. Numerous risk factors for the development of gout have been established, including hyperuricaemia, genetic factors, dietary factors, alcohol consumption, metabolic syndrome, hypertension, obesity, diuretic use and chronic renal disease. Osteoarthritis predisposes to local crystal deposition. Gout appears to be an independent risk factor for all-cause mortality and cardiovascular mortality and morbidity, additional to the risk conferred by its association with traditional cardiovascular risk factors.
doi:10.1186/ar3199
PMCID: PMC3046529  PMID: 21205285
23.  The effect of genome-wide association scan quality control on imputation outcome for common variants 
Imputation is an extremely valuable tool in conducting and synthesising genome-wide association studies (GWASs). Directly typed SNP quality control (QC) is thought to affect imputation quality. It is, therefore, common practise to use quality-controlled (QCed) data as an input for imputing genotypes. This study aims to determine the effect of commonly applied QC steps on imputation outcomes. We performed several iterations of imputing SNPs across chromosome 22 in a dataset consisting of 3177 samples with Illumina 610k (Illumina, San Diego, CA, USA) GWAS data, applying different QC steps each time. The imputed genotypes were compared with the directly typed genotypes. In addition, we investigated the correlation between alternatively QCed data. We also applied a series of post-imputation QC steps balancing elimination of poorly imputed SNPs and information loss. We found that the difference between the unQCed data and the fully QCed data on imputation outcome was minimal. Our study shows that imputation of common variants is generally very accurate and robust to GWAS QC, which is not a major factor affecting imputation outcome. A minority of common-frequency SNPs with particular properties cannot be accurately imputed regardless of QC stringency. These findings may not generalise to the imputation of low frequency and rare variants.
doi:10.1038/ejhg.2010.242
PMCID: PMC3083623  PMID: 21267008
genome-wide association study; imputation; quality control; single nucleotide polymorphism
24.  A HACCP-based approach to mastitis control in dairy herds. Part 1: Development 
Irish Veterinary Journal  2011;64(1):2.
Hazard Analysis and Critical Control Points (HACCP) systems are a risk based preventive approach developed to increase levels of food safety assurance. This is part 1 of a pilot study on the development, implementation and evaluation of a HACCP-based approach for the control of good udder health in dairy cows. The paper describes the use of a novel approach based on a deconstruction of the infectious process in mastitis to identify Critical Control Points (CCPs) and develop a HACCP-based system to prevent and control mastitis in dairy herds. The approach involved the creation of an Infectious Process Flow Diagram, which was then cross-referenced to two production process flow diagrams of the milking process and cow management cycle. The HACCP plan developed, may be suitable for customisation and implementation on dairy farms. This is a logical, systematic approach to the development of a mastitis control programme that could be used as a template for the development of control programmes for other infectious diseases in the dairy herd.
doi:10.1186/2046-0481-64-2
PMCID: PMC3102330  PMID: 21777489
25.  Irish Veterinary Journal goes open access 
Irish Veterinary Journal  2011;64(1):1.
doi:10.1186/2046-0481-64-1
PMCID: PMC3102332  PMID: 21777497

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