Modeling the economic impacts of mobility scores in dairy cows under Irish spring pasture-based management.

Moderate to severe forms of suboptimal mobility on dairy cows are associated with yield losses, whereas mild forms of suboptimal mobility are associated with elevated somatic cell count and an increased risk to be culled. Although the economic consequences of severe forms of suboptimal mobility (also referred as clinical lameness) have been studied extensively, the mild forms are generally ignored. Therefore, the aim of the current study was to determine the economic consequences associated with varying prevalence and forms of suboptimal mobility within spring calving, pasture-based dairy herds. A new submodel predicting mobility scores was developed and integrated within an existing pastured-based herd dynamic model. Using a daily timestep, this model simulates claw disorders, and the consequent mobility score of individual cows. The impact of a cow having varying forms of suboptimal mobility on production and reproduction was simulated. The economic impact was simulated including treatment costs, as well as the production and reproductive impacts of varying levels of suboptimal mobility. Furthermore, different genetic predispositions for mobility issues and their interaction with herd-level management associated with each level of suboptimal mobility were simulated. Overall, 13 scenarios were simulated, representing a typical spring calving, pasture-based dairy herd with 100 cows. The first scenario represents a perfect herd wherein 100% of the cows had mobility score 0 (optimal mobility) throughout the lactation. The remaining 12 scenarios represent a combination of (1) 3 different herd-management levels, and (2) 4 different levels of a genetic predisposition for suboptimal mobility. The analysis showed that a 17% decrease in farm net profit was achieved in the worst outcome (wherein just 5% of the herd had optimal mobility) compared with the perfect herd. This was due to reduced milk yield, increased culling, and increased treatment costs for mobility issues compared the ideal scenario.

Effect of feeding single-dam or pooled colostrum on maternally derived immunity in dairy calves.

The role of colostrum management in providing adequate immunological protection to neonatal calves has been widely investigated, and thresholds for colostrum quality, as well as optimum volume and timing for colostrum feeding have been established. However, limited information is available on the effect of colostrum source (single dam or pooled) on passive immunity, as well as subsequent antibody survival in the calf. This study aimed to assess the effect of feeding single-dam colostrum (own and other dam) or pooled colostrum on transfer of passive immunity, and also investigate the rate of depletion of disease-specific antibodies among dairy calves. In total, 320 cows and 119 dairy heifer calves were enrolled in the study. Calves were blood-sampled immediately after birth and received either own-dam, other-dam, or pooled colostrum. Calves were blood-sampled at 24 h to assess serum IgG concentrations and at monthly intervals thereafter to document disease-specific antibody survival. Mean colostrum IgG concentration was higher for other-dam treatment group, whereas own-dam and pooled treatments were similar. For all treatment groups, the mean IgG concentration was >80 mg/mL, exceeding the quality threshold of 50 mg/mL. Mean calf serum IgG concentration was lower for calves fed pooled colostrum compared with those that received colostrum from a single cow. There was a negative association with 24-h serum IgG and calf birth bodyweight; calves <30 kg at birth had the highest 24-h serum IgG concentration. Survival of antibodies to bovine viral diarrhea, Salmonella infection, leptospirosis, bovine parainfluenza 3 virus, bovine respiratory syncytical virus, rotavirus, and coronavirus was not associated with colostrum source; however, antibodies to infectious bovine rhinotracheitis had a greater period of survival among calves fed own-dam colostrum. We found that feeding single-dam colostrum can thus improve calf immunity through increased serum IgG levels and antibody survival rates. Furthermore, we hypothesize that immune exclusion may occur with pooled colostrum; therefore, providing pooled colostrum may still be a good practice as long as it can be ensured that enough antibodies are absorbed into the blood stream to deal with pathogens calves may encounter because different dams may have antibodies against different strains of viruses and bacteria, yielding cross protection.

What is the current practice for managing patients with chronic limb-threatening ischaemia in vascular surgery services? A survey of UK vascular surgeons.

INTRODUCTION: The Vascular Society of Great Britain and Ireland (VSGBI) Peripheral Arterial Disease Quality Improvement Framework (PAD QIF) stipulates targets for managing patients with chronic limb-threatening ischaemia (CLTI); however, it is unknown whether these are achievable. This survey aims to evaluate contemporary practice for managing CLTI in the UK. METHODS: A questionnaire was developed in conjunction with the VSGBI to survey the management of CLTI and canvass opinions on the PAD QIF. The survey was distributed to all consultant members of the VSGBI and through a targeted social media campaign. RESULTS: Forty-seven consultant vascular surgeons based at 36 arterial centres across the UK responded (response rate from arterial centres = 46%). Only 14.3% of centres provided outpatient consultation within the target of seven days from referral, with only one centre providing revascularisation within the target of seven days from consultation. For inpatient management, 31.6% provided surgical and 23.8% endovascular revascularisation within the target of three days from assessment. While 60% of participants believe the PAD QIF's 5-day 'admitted care' pathway is achievable, only 28.6% thought the 14-day 'non-admitted care' pathway was feasible. Challenges to meeting these targets include the availability of theatre space and angiography lists, and availability of outpatient appointments for patient assessment. CONCLUSIONS: The opinion of UK vascular surgeons indicates that achieving the targets of the PAD QIF represents a major challenge based upon current services. Adapting existing services with a greater focus on providing an 'urgent' model of care may help to potentially overcome these challenges.

Associating mobility scores with production and reproductive performance in pasture-based dairy cows.

Lameness in dairy cows can have significant effects on cow welfare, farm profitability, and the environment. To determine the economic and environmental consequences of lameness, we first need to quantify its effect on performance. The objective of this study, therefore, was to determine the associations of various production and reproductive performance measurements (including milk, fat, and protein yield, somatic cell count, calving interval, cow death, or cow slaughter), and mobility scores in spring-calving, pasture-based dairy cows. We collected mobility scores (0 = good, 1 = imperfect, 2 = impaired, and 3 = severely impaired mobility), body condition scores, and production data for 11,116 cows from 68 pasture-based dairy herds. Linear mixed modeling was used to determine the associations between specific mobility scores and milk, fat and protein yield, and somatic cell count and calving interval. Binomial logistic regression was used to determine the association between mobility score and cow death, or slaughter. Significant yield losses of up to 1.4% of the average yield were associated with mobility score 2 and yield losses of up to 4.7% were associated with mobility score 3 during the early scoring period. Elevated somatic cell count was associated with all levels of suboptimal mobility during the late scoring period. Cows with a mobility score of 2 during the early scoring period were associated with longer calving interval length, whereas only cows with a mobility score of 3 during the late scoring period were associated with longer calving interval length. Cows with a mobility score ≥1 were more likely to be culled during both scoring periods. Our study, therefore, shows an association between specific mobility scores and production and reproductive performance in spring-calving, pasture-based dairy cows scored during the summer grazing period.

Report of a Delphi exercise to inform the design of a research programme on screening for thoracic aortic disease.

OBJECTIVES: To inform the design of a clinical trial of a targeted screening programme for relatives of individuals affected by thoracic aortic disease, we performed a consensus exercise as to the acceptability of screening, the optimal sequence and choice of tests, long-term patient management, and choice of trial design. METHODS: Working with the Aortic Dissection Awareness UK & Ireland patient association, we performed a Delphi exercise with clinical experts, patients, and carers, consisting of three rounds of consultation followed by a final multi-stakeholder face-to-face workshop. RESULTS: Thirty-five experts and 84 members of the public took part in the surveys, with 164 patients and clinicians attending the final workshop. There was substantial agreement on the need for a targeted screening pathway that would employ a combined approach (imaging + genetic testing). The target population would include the first- and second-degree adult (> 15 years) relatives, with no upper age limit of affected patients. Disagreement persisted about the screening process, sequence, personnel, the imaging method to adopt, computed tomography (CT) scan vs magnetic resonance imaging (MRI), and the specifics of a potential trial, including willingness to undergo randomisation, and measures of effectiveness and acceptability. CONCLUSION: A Delphi process, initiated by patients, identified areas of uncertainty with respect to behaviour, process, and the design of a targeted screening programme for thoracic aortic disease that requires further research prior to any future trial.

Cow and herd-level risk factors associated with mobility scores in pasture-based dairy cows.

Lameness in dairy cows is an area of concern from an economic, environmental and animal welfare point of view. While the potential risk factors associated with suboptimal mobility in non-pasture-based systems are evident throughout the literature, the same information is less abundant for pasture-based systems specifically those coupled with seasonal calving, like those in Ireland. Therefore, the objective of this study was to determine the potential risk factors associated with specific mobility scores (0 = good, 1 = imperfect, 2 = impaired, and 3 = severely impaired mobility) for pasture-based dairy cows. Various cow and herd-level potential risk factors from Irish pasture-based systems were collected and analyzed for their association with suboptimal mobility, whereby a mobility score of 0 refers to cows with optimal mobility and a mobility score ≥ 1 refers to a cow with some form of suboptimal mobility. Combined cow and herd-level statistical models were used to determine the increased or decreased risk for mobility score 1, 2, and 3 (any form of suboptimal mobility) compared to the risk for mobility score 0 (optimal mobility), as the outcome variable and the various potential risk factors at both the cow and herd-level were included as predictor type variables. Cow-level variables included body condition score, milk yield, genetic predicted transmitting ability for 'lameness', somatic cell score, calving month and cow breed. Herd-level variables included various environmental and management practices on farm. These analyses have identified several cow-level potential risk factors (including low body condition score, high milk yield, elevated somatic cell count, stage of lactation, calving month, and certain breed types), as well as various herd-level potential risk factors (including the amount of time taken to complete the milking process, claw trimmer training, farm layout factors and foot bathing practices) which are associated with suboptimal mobility. The results of this study should be considered by farm advisors when advising and implementing a cow/herd health program for dairy cows in pasture-based systems.

The utilisation of vascular limb salvage services in the assessment and management of chronic limb-threatening ischaemia and diabetic foot ulceration: A systematic review.

Specialist vascular limb salvage services have gained prominence as a new model of care to help overcome barriers which exist in the management of patients with chronic limb-threatening ischaemia (CLTI) and/or diabetic foot ulceration (DFU). This systematic review aims to explore the nature of reported services, investigate their outcome in the management of CLTI/DFU, and assess the scope and quality of the evidence base to help make recommendations for future practice and research. A systematic search of MEDLINE, Embase, The Cochrane Library, Scopus and CINAHL, from 1st January 1995 to 18th January 2019, was performed. Specialist vascular limb salvage services were defined as those services conforming to the definition of "centres of excellence" within the 2019 Global Vascular Guidelines. A study protocol was registered at the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42019123325). In total, 2260 articles were screened, with 12 articles (describing 11 services) included in a narrative synthesis. All services ran akin to the "toe-and-flow" model, with a number of services having additional core input from diabetology, microbiology, allied health professionals and/or internal/vascular medicine. Methodological weaknesses were identified within the design of the included articles and only one was deemed of high quality. The inception of services was associated with improved rates of major amputation; however, no significant changes in minor amputation or mortality rates were identified. Further research should adopt more a standardised study design and outcomes measures in order to improve the quality of evidence within the literature.

Associating cow characteristics with mobility scores in pasture-based dairy cows.

The quality of dairy cow mobility can have significant welfare, economic, and environmental consequences that have yet to be extensively quantified for pasture-based systems. The objective of this study was to characterize mobility quality by examining associations between specific mobility scores, claw disorders (both the type and severity), body condition score (BCS), and cow parity. Data were collected for 6,927 cows from 52 pasture-based dairy herds, including mobility score (0 = optimal mobility; 1, 2, or 3 = increasing severities of suboptimal mobility), claw disorder type and severity, BCS, and cow parity. Multinomial logistic regression was used for analysis. The outcome variable was mobility score, and the predictor variables were BCS, type and severity of claw disorders, and cow parity. Three models were run, each with 1 reference category (mobility score 0, 1, or 2). Each model also included claw disorders (overgrown claw, sole hemorrhage, white line disease, sole ulcer, and digital dermatitis), BCS, and cow parity as predictor variables. The presence of most types of claw disorders had odds ratios >1, indicating an increased likelihood of a cow having suboptimal mobility. Low BCS (BCS <3.00) was associated with an increased risk of a cow having suboptimal mobility, and relatively higher parity was also associated with an increased risk of suboptimal mobility. These results confirm an association between claw disorders, BCS, cow parity, and dairy cow mobility score. Therefore, mobility score should be routinely practiced to identify cows with slight deviations from the optimal mobility pattern and to take preventive measures to keep the problem from worsening.

Genetic variability in the humoral immune response to bovine herpesvirus-1 infection in dairy cattle and genetic correlations with performance traits.

Bovine herpesvirus-1 (BoHV-1) is a viral pathogen of global significance that is known to instigate several diseases in cattle, the most notable of which include infectious bovine rhinotracheitis and bovine respiratory disease. The genetic variability in the humoral immune response to BoHV-1 has, to our knowledge, not ever been quantified. Therefore, the objectives of the present study were to estimate the genetic parameters for the humoral immune response to BoHV-1 in Irish female dairy cattle, as well as to investigate the genetic relationship between the humoral immune response to BoHV-1 with milk production performance, fertility performance, and animal mortality. Information on antibody response to BoHV-1 was available to the present study from 2 BoHV-1 sero-prevalence research studies conducted between the years 2010 to 2015, inclusive; after edits, BoHV-1 antibody test results were available on a total of 7,501 female cattle from 58 dairy herds. National records of milk production (i.e., 305-d milk yield, fat yield, protein yield, and somatic cell score; n = 1,211,905 milk-recorded cows), fertility performance (i.e., calving performance, pregnancy diagnosis, and insemination data; n = 2,365,657 cows) together with animal mortality data (i.e., birth, farm movement, death, slaughter, and export events; n = 12,853,257 animals) were also available. Animal linear mixed models were used to quantify variance components for BoHV-1 as well as to estimate genetic correlations among traits. The estimated genetic parameters for the humoral immune response to BoHV-1 in the present study (i.e., heritability range: 0.09 to 0.16) were similar to estimates previously reported for clinical signs of bovine respiratory disease in dairy and beef cattle (i.e., heritability range: 0.05 to 0.11). Results from the present study suggest that breeding for resistance to BoHV-1 infection could reduce the incidence of respiratory disease in cattle while having little or no effect on genetic selection for milk yield or milk constituents (i.e., genetic correlations ranged from -0.13 to 0.17). Moreover, even though standard errors were large, results also suggest that breeding for resistance to BoHV-1 infection may indirectly improve fertility performance while also reducing the incidence of mortality in older animals (i.e., animals >182 d of age). Results can be used to inform breeding programs of potential genetic gains achievable for resistance to BoHV-1 infection in cattle.

Cardiovascular Risk Reduction is Important for Improving Patient and Graft Survival After Ligation and Bypass Surgery for Popliteal Artery Aneurysm.

OBJECTIVES: To report outcomes following ligation and bypass (LGB) surgery for popliteal artery aneurysm (PAA) and study factors influencing patient and graft survival. MATERIALS AND METHODS: A retrospective review of patients undergoing LGB surgery for PAA between September 1999 and August 2012 at a tertiary referral vascular unit was performed. Primary graft patency (PGP), primary-assisted graft patency (PAGP), and secondary graft patency (SGP) rates were calculated using survival analyses. Patient, graft aneurysm-free survival (GAFS), aneurysm reperfusion-free survival (ARFS), and amputation-free survival (AFS) rates were also calculated. Log-rank testing and Cox proportional hazards modeling were used to perform univariate and multivariate analysis of influencing factors, respectively. RESULTS: Eighty-four LGB repairs in 69 patients (mean age 71.3 years, 68 males) were available for study. The 5-year PGP, PAGP, SGP, and patient survival rates were 58.1%, 84.4%, 85.2%, and 81.1%, respectively. On multivariate analysis, the principal determinants of PGP were urgency of operation ( P = .009) and smoking status ( P = .019). The principal determinants of PAGP were hyperlipidemia status ( P = .048) and of SGP were hyperlipidemia ( P = .042) and cerebrovascular disease (CVD) status ( P = .045). The principal determinants of patient survival were previous myocardial infarction ( P = .004) and CVD ( P = .001). The 5-year GAFS, ARFS, and AFS rates were 87.9%, 91.6%, and 96.1%, respectively. CONCLUSION: This study has shown that traditional cardiovascular risk factors, such as a smoking and ischemic heart disease, are the most important predictors of early graft failure and patient death following LGB surgery for PAA.

Characterization of an X-chromosomal non-mosaic monosomy (59, X0) dairy heifer detected using routinely available single nucleotide polymorphism genotype data.

Evidence exists from a range of species on the impact of karyotype abnormalities on reproductive performance. Despite this, cytogenetic analyses of cattle, especially females, are not routinely undertaken. Genome-wide single nucleotide polymorphism (SNP) genotype data are now, however, routinely being generated in many species globally at a relatively low cost. The objective of the present study was to evaluate the potential of routinely available SNP genotype data to identify sex-chromosome aberrations using X chromosome monosomy 59,X0 as a case study for illustration. A single 2.5-yr old Holstein-Friesian heifer was detected with a mean allelic intensity of SNP on the X chromosome almost 17 standard deviations less than the mean of other genotyped females ( = 103,326). Following cytogenetic analysis (10 replicates by karyotyping and a further 140 by FISH), the female was deduced to be a non-mosaic 59,X0. The female had never produced a calf and, although gross examination revealed no physical abnormalities, she was smaller in size than expected based on her breed and age. Given the age of the animal at slaughter, the uterus and uterine tubes appeared immature and inactive. The oviduct appeared normal while the single ovary present contained a markedly reduced number of follicles. There was, however, some evidence of prior ovulation and formation of corpora lutea. The approach proposed in the present study to identify allosome aneuploidy from routinely available genotype data can be used to screen for such abnormalities at no additional cost to the breeder or producer.

Post-Carotid Endarterectomy Hypertension. Part 1: Association with Pre-operative Clinical, Imaging, and Physiological Parameters.

OBJECTIVE/BACKGROUND: Post-endarterectomy hypertension (PEH) is a well recognised, but poorly understood, phenomenon after carotid endarterectomy (CEA) that is associated with post-operative intracranial haemorrhage, hyperperfusion syndrome, and cardiac complications. The aim of the current study was to identify pre-operative clinical, imaging, and physiological parameters associated with PEH. METHODS: In total, 106 CEA patients undergoing CEA under general anaesthesia underwent pre-operative evaluation of 24 hour ambulatory arterial blood pressure (BP), baroreceptor sensitivity, cerebral autoregulation, and transcranial Doppler measurement of cerebral blood flow velocity (CBFv) and pulsatility index. Patients who met pre-existing criteria for treating PEH after CEA (systolic BP [SBP] > 170 mmHg without symptoms or SBP > 160 mmHg with headache/seizure/neurological deficit) were treated according to a previously established protocol. RESULTS: In total, 40/106 patients (38%) required treatment for PEH at some stage following CEA (26 in theatre recovery [25%], 27 while on the vascular surgical ward [25%]), while seven (7%) had SBP surges > 200 mmHg back on the ward. Patients requiring treatment for PEH had a significantly higher pre-operative SBP (144 ± 11 mmHg vs. 135 ± 13 mmHg; p < .001) and evidence of pre-existing impairment of baroreceptor sensitivity (3.4 ± 1.7 ms/mmHg vs. 5.3 ± 2.8 ms/mmHg; p = .02). However, PEH was not associated with any other pre-operative clinical features, CBFv, or impaired cerebral haemodynamics. Paradoxically, autoregulation was better preserved in patients with PEH. All four cases of hyperperfusion associated symptoms were preceded by PEH. Length of hospital stay was significantly increased in patients with PEH (p < .001). CONCLUSION: In this study, where all patients underwent CEA under general anaesthesia, PEH was associated with poorly controlled pre-operative BP and impaired baroreceptor sensitivity, but not with other peripheral or central haemodynamic parameters, including impaired cerebral autoregulation.

Investigations and implications of associations between mycobacterial purified protein derivative hypersensitivity and MAP-antibody ELISA in Irish dairy cows.

Intradermal testing, involving administration of purified protein derivative (PPD), to elicit a delayed hypersensitivity (DTH) response, is used as a diagnostic tool for bovine tuberculosis (bTB) and to aid in the identification of exposure to Mycobacterium avium subspecies paratuberculosis (MAP), the causative agent of Johne's disease (JD). Further research is required to increase the diagnostic value of skin testing for MAP. The aim of this study was to investigate if animals showing DTH reactions to PPD had an associated increase in MAP ELISA response, thereby identifying potential cases of sub-clinical JD. A 139-cow dairy herd was recruited to the study. During the mandatory annual bTB test, skin thickness measurements (mm) were recorded at the site of avian and bovine PPD administration. Cows were categorised based on recording no DTH, DTH at both PPD administration sites and DTH at one PPD site only. Blood samples were collected pre and post bTB testing, and ELISA tested. Generalised estimating equations were performed to identify associations between DTH responses and MAP ELISA results. Significant associations were identified between PPD DTH responses and MAP ELISA readings. Animals with DTH at both avian and bovine PPD sites were most likely to test ELISA positive in the post-PPD period relative to other categories. Further research is required to identify whether skin thickness increases post-PPD and associated increase in ELISA response, identifies animals previously exposed to MAP, or if results are due to cross reactivity.

Reporting individual surgeon outcomes does not lead to risk aversion in abdominal aortic aneurysm surgery.

INTRODUCTION Reporting surgeons' outcomes has recently been introduced in the UK. This has the potential to result in surgeons becoming risk averse. The aim of this study was to investigate whether reporting outcomes for abdominal aortic aneurysm (AAA) surgery impacts on the number and risk profile (level of fitness) of patients offered elective treatment. METHODS Publically available National Vascular Registry data were used to compare the number of AAAs treated in those centres across the UK that reported outcomes for the periods 2008-2012, 2009-2013 and 2010-2014. Furthermore, the number and characteristics of patients referred for consideration of elective AAA repair at a single tertiary unit were analysed yearly between 2010 and 2014. Clinic, casualty and theatre event codes were searched to obtain all AAAs treated. The results of cardiopulmonary exercise testing (CPET) were assessed. RESULTS For the 85 centres that reported outcomes in all three five-year periods, the median number of AAAs treated per unit increased between the periods 2008-2012 and 2010-2014 from 192 to 214 per year (p=0.006). In the single centre cohort study, the proportion of patients offered elective AAA repair increased from 74% in 2009-2010 to 81% in 2013-2014, with a maximum of 84% in 2012-2013. The age, aneurysm size and CPET results (anaerobic threshold levels) for those eventually offered elective treatment did not differ significantly between 2010 and 2014. CONCLUSIONS The results do not support the assumption that reporting individual surgeon outcomes is associated with a risk averse strategy regarding patient selection in aneurysm surgery at present.

Patients with Small Abdominal Aortic Aneurysm are at Significant Risk of Cardiovascular Events and this Risk is not Addressed Sufficiently.

BACKGROUND: Patients with abdominal aortic aneurysm (AAA) are at significant risk of cardiovascular (CV) events. Recent implementation of AAA-screening means thousands of patients are now diagnosed with small-AAA; however, CV risk factors are not always addressed. This study aimed at assessing and quantifying the CV characteristics of patients with small AAA following the introduction of screening programmes. METHODS: CV profiles of 384 men with a small AAA (<55 mm diameter) were assessed through the United Kingdom Aneurysm Growth Study (UKAGS), a nationwide prospective cohort study of men with small AAA. A prospective local cohort of an additional 142 patients with small AAA with available blood pressure (BP) and lipid profiles was also included and followed-up for 1 year. RESULTS: In the UKAGS population, 54% were current and 30% ex-smokers; 58% were hypertensive and 54% hypercholesterolaemic. In the local group, 54% were current and 40% were ex-smokers, and 94% were hypertensive. Patients were not more likely to receive CV medication after entering AAA surveillance in either group. All local patients were clustered "high-risk" for future CV events based on the Framingham score (mean 21.8%, 95% CI 20.0-23.6), JBS-2 (16.3%, 14.7-17.9) and ASSIGN (25.2%, 22.7-27.7). No change was seen in systolic BP levels between baseline and 1 year (140.9 mmHg vs. 142.5 mmHg, p=.435). A rise was seen in cholesterol (4.0 mmol-4.2 mmol, p<.0001) values at 1 year. CONCLUSIONS: This study suggests that patients with small AAA are at significant risk for developing CV events and this is not currently addressed, which is evident by the "high-risk" CV risk profiles of these patients despite being in AAA surveillance. Design and implementation of a CV risk reduction programme tailored for this population is necessary.

Genetic parameters for both a liver damage phenotype caused by and antibody response to phenotype in dairy and beef cattle.

is a helminth parasite of economic importance to the global cattle industry, with documented high international herd prevalence. The objective of the present study was to generate the first published genetic parameter estimates for liver damage caused by as well as antibody response to in cattle. Abattoir data on the presence of live , or -damaged livers, were available between the years 2012 and 2015, inclusive. A second data set was available on cows from 68 selected dairy herds with a blood ELISA test for antibody response to in autumn 2015. Animals were identified as exposed by using herd mate phenotype, and only exposed animals were retained for analysis. The abattoir data set consisted of 20,481 dairy cows and 75,041 young dairy and beef animals, whereas the study herd data set consisted of 6,912 dairy cows. (Co)variance components for phenotypes in both data sets were estimated using animal linear mixed models. Fixed effects included in the model for both data sets were contemporary group, heterosis coefficient, recombination loss coefficient, parity, age relative to parity/age group, and stage of lactation. An additional fixed effect of abattoir by date of slaughter was included in the model for the analysis of the abattoir data. Direct additive genetic effects and a residual effect were included as random effects for all analyses. After data edits, the prevalence of liver damage caused by in cows and young cattle was 47% and 20%, respectively. The prevalence of a positive antibody response to in cows from the study herd data was 36% after data edits. The heritability of as a binary trait for dairy cows in abattoir data and study herd data was 0.03 ± 0.01 and 0.09 ± 0.02, respectively; heritability in young cattle was 0.01 ± 0.005. The additive genetic SD of as a binary trait was 0.069 and 0.050 for cows and young cattle from the abattoir data, respectively, and 0.112 from the study herd cows. The genetic correlation between liver damage caused by in young cattle and cows from the abattoir data was 0.94 ± 0.312 and the genetic correlation between liver damage caused by in cows and positive antibody response to in cows in the study herd data was 0.37 ± 0.283.

Six-year longitudinal study of Fasciola hepatica bulk milk antibody ELISA in the dairy dense region of the Republic Ireland.

Completion of the F. hepatica lifecycle is dependent on suitable climatic conditions for development of immature stages of the parasite, and its snail intermediate host. Few investigations have been conducted regarding temporal variations in F. hepatica status in Irish dairy herds. The current study aimed to conduct a longitudinal study examining annual and seasonal trends in bulk milk seropositivity over six years, while also investigating associations with soil temperature, rainfall and flukicide treatment. Monthly bulk milk samples (BTM) were submitted by 28 herds between March 2009 and December 2014. In all, 1337 samples were analysed using a Cathepsin L1 ELISA. Soil temperature, rainfall and management data were obtained for general estimating equation and regression analyses. A general decrease in milk seropositivity was observed over the six year study period and was associated with an increased likelihood of treating for liver fluke (OR range=2.73-6.96). Annual and seasonal analyses of rainfall and F. hepatica BTM status yielded conflicting results. Higher annual rainfall (>1150mm) yielded a lower likelihood of being BTM positive than annual rainfall of <1000mm (OR=0.47; P=0.036). This was most likely due to farmers being more proactive in treating for F. hepatica in wetter years, although a 'wash effect' by high rainfall of the free living stages and snails cannot be ruled out. Higher seasonal rainfall (>120mm), however, was associated with increased ELISA S/P% values (Coefficient=9.63S/P%; P=0.001). Soil temperature was not found to influence F. hepatica to the same extent as rainfall and may reflect the lack of severe temperature fluctuations in Ireland. Flukicides active against both immature and mature F. hepatica were approximately half as likely to record a positive F. hepatica herd BTM status than a flukicide active against only the mature stage of the parasite (OR≅0.45; P<0.01). This study highlights the importance of examining both annual and seasonal F. hepatica data, which can vary significantly. Additionally, it highlights the progress that can be achieved in fluke control by application of a continuous BTM monitoring program.

Meta-analysis of Outcomes Following Aneurysm Repair in Patients with Synchronous Intra-abdominal Malignancy.

OBJECTIVES: The management of concomitant intra-abdominal malignancy (IAM) and abdominal aortic aneurysm (AAA) remains a challenge, even though malignancy is common in an elderly population. By means of systematic review and meta-analysis, the aim was to investigate outcomes in patients undergoing open (OAR) or endovascular AAA repair (EVAR) that have a concomitant malignancy. METHODS: A systematic literature review was performed (Medline and EMBASE databases) to identify all series reporting outcomes of AAA repair (OAR or EVAR) in patients with concomitant IAM. Meta-analysis was applied to assess mortality and major morbidity at 30 days and long term. RESULTS: The literature review identified 36 series (543 patients) and the majority (18 series) reported on patients with colorectal malignancy and AAA. Mean weighted mortality for OAR at 30 days was 11% (95% CI: 6.6% to 17.9%); none of the EVAR patients died peri-operatively. The weighted 30-day major complication rate for EVAR was 20.4% (10.0-37.4%) and for OAR it was 15.4% (7.0-30.8%). Most patients had their AAA and malignancy treated non-simultaneously (56.6%, 95% CI, 42.1-70.1%). In the EVAR cohort, three patients (4.6%) died at last follow-up (range 24-64 months). In the OAR cohort 23 (10.6%) had died at last follow up (range from 4 to 73 months). CONCLUSION: In this meta-analysis, OAR was associated with significant peri-operative mortality in patients with an IAM. EVAR should be the first-line modality of AAA repair. The majority of patients were not treated simultaneously for the two pathologies, but further investigation is necessary to define the optimal timing for each procedure and malignancy.

Gene and Protein Expression of Chemokine (C-C-Motif) Ligand 19 is Upregulated in Unstable Carotid Atherosclerotic Plaques.

OBJECTIVE/BACKGROUND: The aim was to investigate the expression of genes associated with carotid plaque instability and their protein products at a local and systemic level. METHODS: Carotid plaques from 24 patients undergoing carotid endarterectomy (CEA) were classified as stable or unstable using clinical, histological, ultrasound, and transcranial Doppler criteria, and compared using whole genome microarray chips. Initial results of differentially expressed genes were validated by quantitative reverse transcriptase polymerase chain reaction in an independent group of 96 patients undergoing CEA. The protein product of genes significantly differentially expressed between patients with stable and unstable plaques were analysed by plaque immunohistochemistry and serum protein quantification by enzyme-linked immunosorbent assay on a further independent cohort. RESULTS: Expression of chemokine (c-c-motif) ligand 19 (CCL19) was significantly upregulated in plaques from patients with clinically unstable disease (p < .001). Cathepsin G expression was upregulated in histologically unstable plaques (p = .04). Serum concentration of CCL19 was significantly higher in patients with clinically unstable plaques (p = .02). Immunohistochemical staining for CCL19 demonstrated positive staining in histologically and clinically unstable plaques (p = .03). CCL19 also co-localised with CD3+ T-cell lymphocytes in the core region, around where CCL19 was expressed. CONCLUSIONS: CCL19 is significantly overexpressed in patients with unstable carotid atherosclerotic plaques and may be a possible novel biomarker for identifying high-risk patients in whom more urgent intervention may be indicated.

Microarray-based Gene Expression Profiling of Abdominal Aortic Aneurysm.

OBJECTIVE/BACKGROUND: Microarray-based gene expression profiling studies may detect transcriptional signatures carrying prognostic value in abdominal aortic aneurysms (AAA). A gene expression profiling study was conducted to compare individuals with AAA with screened controls. METHODS: The peripheral blood transcriptome was compared between 12 individuals with AAA and 12 age- and sex-matched controls using microarray. Validation by Taqman real-time quantitative (qPCR) was performed in an independent group as described. Peripheral blood RNA was hybridized to Illumina microarrays, each representing 37,846 genes, allowing comparison of gene expression between cases and controls. Eleven differentially expressed genes were re-quantified by qPCR in the independent group with AAA (n = 95), controls (n = 92), pre- and postendovascular AAA repair (EVAR, n = 31); or open AAA repair (n = 13), AAA wall biopsies (n = 11), and in matched smooth muscle cultures (n = 7). RESULTS: Microarray detected 47 significantly differentially expressed genes in AAA after correction for multiple testing (p < .05). These genes conferred roles in regulation of apoptosis, proteolysis, the electron transport chain, leukocyte migration, and the humoral immune response. Gene quantification in the independent group demonstrated three genes to be downregulated in AAA compared with controls: MSN, PSMB10, and STIM1; however, their expression remained unchanged post-AAA repair. PSMB10 was the only gene conferring a consistent direction of effect in both the discovery and validation analyses (downregulated). EIF3G, SIVA, PUF60, CYC1, FIBP, and CARD8 were downregulated post-EVAR. Expression of all 11 genes of interest was detected in aortic biopsies and matched smooth muscle cultures. CONCLUSION: This study demonstrates differential expression of transcripts in peripheral blood of individuals with AAA, with functional roles in proteolysis, inflammation, and apoptotic processes. These were modulated by aneurysm exclusion from the circulation and expressed in matched aortic biopsies and smooth muscle cultures. These observations further support the key roles for these pathways in the pathogenesis of AAA.