Association between Loin Ultimate pH and Plasma Indicators of Pre-Slaughter Stressors in Australian Lamb

The purpose of this study was to test if associations exist between plasma indicators of acute and chronic stress and lamb ultimate pH. Blood was collected at exsanguination from 2,877 lambs from the Meat and Livestock Australia Genetic Research flock with a suite of indicators analyzed. Ultimate pH was measured in the loin (M. longissimus lumborum) at 24 h post-slaughter. There was a positive association (

Association between Loin Ultimate pH and Plasma Indicators of Pre-Slaughter Stressors in Australian Lamb

The purpose of this study was to test if associations exist between plasma indicators of acute and chronic stress and lamb ultimate pH. Blood was collected at exsanguination from 2,877 lambs from the Meat and Livestock Australia Genetic Research flock with a suite of indicators analyzed. Ultimate pH was measured in the loin (M. longissimus lumborum) at 24 h post-slaughter. There was a positive association (P < 0.05) between ultimate pH and plasma glucose and lactate concentrations, which indicates that opportunities exist to reduce variation in ultimate pH by reducing stress in the pre-slaughter period. These effects were small by comparison to production factors, however further understanding of how to best manage lambs in the pre-slaughter period is required to minimize stress and maximize lamb wellbeing and meat quality

Translational Medicine and Patient Safety in Europe:TRANSFoRm - Architecture for the Learning Health System in Europe

The Learning Health System (LHS) describes linking routine healthcare systems directly with both research translation and knowledge translation as an extension of the evidence-based medicine paradigm, taking advantage of the ubiquitous use of electronic health record (EHR) systems. TRANSFoRm is an EU FP7 project that seeks to develop an infrastructure for the LHS in European primary care. Methods. The project is based on three clinical use cases, a genotype-phenotype study in diabetes, a randomised controlled trial with gastroesophageal reflux disease, and a diagnostic decision support system for chest pain, abdominal pain, and shortness of breath. Results. Four models were developed (clinical research, clinical data, provenance, and diagnosis) that form the basis of the projects approach to interoperability. These models are maintained as ontologies with binding of terms to define precise data elements. CDISC ODM and SDM standards are extended using an archetype approach to enable a two-level model of individual data elements, representing both research content and clinical content. Separate configurations of the TRANSFoRm tools serve each use case. Conclusions. The project has been successful in using ontologies and archetypes to develop a highly flexible solution to the problem of heterogeneity of data sources presented by the LHS

Predicting phenotypes of beef eating quality traits

Introduction: Phenotype predictions of beef eating quality for individual animals could be used to allocate animals to longer and more expensive feeding regimes as they enter the feedlot if they are predicted to have higher eating quality, and to sort carcasses into consumer or market value categories. Phenotype predictions can include genetic effects (breed effects, heterosis and breeding value), predicted from genetic markers, as well as fixed effects such as days aged and carcass weight, hump height, ossification, and hormone growth promotant (HGP) status. Methods: Here we assessed accuracy of phenotype predictions for five eating quality traits (tenderness, juiciness, flavour, overall liking and MQ4) in striploins from 1701 animals from a wide variety of backgrounds, including Bos indicus and Bos taurus breeds, using genotypes and simple fixed effects including days aged and carcass weight. The genetic components were predicted based on 709k single nucleotide polymorphism (SNP) using BayesR model, which assumes some markers may have a moderate to large effect. Fixed effects in the prediction included principal components of the genomic relationship matrix, to account for breed effects, heterosis, days aged and carcass weight. Results and Discussion: A model which allowed breed effects to be captured in the SNP effects (e.g., not explicitly fitting these effects) tended to have slightly higher accuracies (0.43-0.50) compared to when these effects were explicitly fitted as fixed effects (0.42-0.49), perhaps because breed effects when explicitly fitted were estimated with more error than when incorporated into the (random) SNP effects. Adding estimates of effects of days aged and carcass weight did not increase the accuracy of phenotype predictions in this particular analysis. The accuracy of phenotype prediction for beef eating quality traits was sufficiently high that such predictions could be useful in predicting eating quality from DNA samples taken from an animal/carcass as it enters the processing plant, to enable optimal supply chain value extraction by sorting product into markets with different quality. The BayesR predictions identified several novel genes potentially associated with beef eating quality

The Problem with Big Data: Operating on Smaller Datasets to Bridge the Implementation Gap

Big datasets have the potential to revolutionize public health. However, there is a mismatch between the political and scientific optimism surrounding big data and the public’s perception of its benefit. We suggest a systematic and concerted emphasis on developing models derived from smaller datasets to illustrate to the public how big data can produce tangible benefits in the long term. In order to highlight the immediate value of a small data approach, we produced a proof-of-concept model predicting hospital length of stay. The results demonstrate that existing small datasets can be used to create models that generate a reasonable prediction, facilitating health-care delivery. We propose that greater attention (and funding) needs to be directed toward the utilization of existing information resources in parallel with current efforts to create and exploit “big data.

Slower Decline in C-Reactive Protein after an Inflammatory Insult Is Associated with Longer Survival in Older Hospitalised Patients

Background Enhancing biological resilience may offer a novel way to prevent and ameliorate disease in older patients. We investigated whether changes in C-reactive protein (CRP), as a dynamic marker of the acute inflammatory response to diverse stressors, may provide a way to operationalize the concept of resilience in older adults. We tested this hypothesis by examining whether such changes could predict prognosis by identifying which individuals are at greater risk of 6-month mortality. Methods Analysis of prospective, routinely collected datasets containing data on hospitalization, clinical chemistry and rehabilitation outcomes for rehabilitation inpatients between 1999 and 2011. Maximum CRP response during acute illness and CRP recovery indices (time and slope of CRP decay to half maximum, and t

Genetic associations with sporadic cerebral small vessel disease

Background: Cerebral small vessel disease (SVD) causes substantial cognitive, psychiatric and physical disabilities. Despite its common nature, SVD pathogenesis and molecular mechanisms remain poorly understood, and prevention and treatment are probably suboptimal. Identifying the genetic determinants of SVD will improve understanding and may help identify novel treatment targets. The aim of this thesis is to better understand genetic associations with SVD through investigating its pathological, radiological and clinical phenotypes. Methods: To unravel the genetic associations with SVD, I used three complementary approaches. First, I performed a systematic review looking at existing intracerebral haemorrhage (ICH) classification systems and their reliability, to help inform future studies of ICH genetics. Second, I performed a series of systematic reviews and meta-analyses, investigating associations between genetic polymorphisms and histopathologically confirmed cerebral amyloid angiopathy (CAA). Third, I performed meta-analyses of existing genome-wide datasets to determine associations of >1000 common single nucleotide polymorphisms (SNP) in the COL4A1/COL4A2 genomic region with clinico-radiological SVD phenotypes: ICH and its subtypes, ischaemic stroke and its subtypes, and white matter hyperintensities. Results: The reliability of existing ICH classification systems appeared excellent in eight studies conducted in specialist centres with experienced raters, although these existing systems have several limitations. In my systematic evaluation of CAA genetics, meta-analyses of 24 studies including 3520 participants showed robust evidence for a dose-dependent association between APOE ɛ4 and histopathological CAA. There was, however, no convincing association between APOE ɛ2 and presence of CAA in a meta-analysis of 11 studies including 1640 participants. Meta-analyses of five studies including 497 participants showed, contrary to an existing popular hypothesis, that while APOE 4 may increase the risk of developing severe CAA vasculopathy, there is no clear evidence to support a role of ɛ2. There were few data about the role of APOE in hereditary CAA, but in the three studies that had looked at this, there was no evidence for an association between APOE ɛ4 and CAA severity. There were too few studies and participants to draw firm conclusions about the effect of non-APOE ε2/ε3/ε4 genetic polymorphisms on CAA, but there were positive associations with TGF-β1, TOMM40 and CR1 genes in four studies. Finally, in my meta-analyses of the COL4A1/COL4A2 genomic region, three intronic SNPs in COL4A2 were associated with SVD phenotypes: significantly with deep ICH, and suggestively with lacunar ischaemic stroke and WMH. Conclusions: I have shown that while existing ICH classification systems appear to have very good reliability, further research is needed to determine their performance in different settings. For large population-based prospective studies of ICH genetics, anatomical systems are likely to be more feasible, scalable and appropriate, although they have limitations and will need to be further developed. Using systematic reviews and meta-analyses, I have confirmed a dose-related association between APOE ɛ4 and histopathological CAA, but also demonstrated that, despite popular acceptance, there is insufficient data to draw firm conclusions about the association with APOE ɛ2. I found some positive associations with CAA in other genes, which merit replication in further larger studies, and showed that there is currently insufficient data about the role of APOE in hereditary CAA. Finally, I identified a novel association between a locus in a known hereditary SVD gene – COL4A2 – and sporadic SVD. This highlights a new and successful approach for selecting candidate genes and can be expanded in future studies to include other known hereditary SVD genes

Selection for muscling affects carbohydrate and fatty acid metabolism in beef cattle

Genetic selection to enhance muscularity in beef cattle is desirable to increase retail beef yield and the profitability of the beef industry. However it is unknown how selection for greater muscling will impact on intermediary and muscle energy metabolism which may influence certain attributes of meat quality. In order to assess these impacts of selection for greater muscling in cattle, the physiological mechanisms that underpin the increase in retail beef yield must be identified. This thesis examined the impact of selection for greater muscling on: retail beef yield; muscle glycogen; whole body insulin responsiveness; adrenaline responsiveness of muscle, adipose and liver tissue; and proportion of glycolytic and oxidative myofibres and enzyme activities. This study used 11 high (High), 10 low (Low) and 3 high muscled steers with a myostatin mutation (HighHet) from an Angus herd which had been visually selected for divergence in muscling over 15 years. The results of the yield test performed at bone-out showed that the HighHet and High muscled steers were the highest yielding with the lowest proportion of fat, while the Low muscling animals were the lowest yielding with the highest proportion of fat. Muscle glycogen and lactate concentration were analysed from four muscle biopsies, taken between 18 and 24 months of age, from the m. semimembranosus (SM), m. semitendinosus (ST) and m. longissimus thoracis et lumborum (LTL) of each animal. The muscle glycogen concentrations which were 6.1% higher in the High steers compared to the Low animals while the HighHet did not differ from either group. The effect of selection for muscling on whole body insulin responsiveness was measured using the hyperinsulineamic-euglyceamic clamp technique. Insulin was constantly infused at 2 levels, glucose was concurrently infused to maintain euglyceamia, and the steady-state glucose infusion rate (SSGIR) indicated insulin responsiveness. At the low insulin infusion rate of 0.6 mU/kg/min, the SSGIR was 73% higher for the High muscling genotype animals when compared to the Low. At the high insulin infusion rate of 6.0 mU/kg/min, these differences were proportionately less with the High and the HighHet genotypes having only 27% and 34% higher SSGIR than the Low muscled genotype. The High muscled cattle also had 30% higher plasma IGF-1 concentrations compared to the Low muscled cattle. The increased whole body insulin responsiveness in combination with higher IGF-1 concentrations in the High muscled steers is likely to initiate a greater level of protein synthesis, which may partially explain the increased muscle accretion in these animals. Increased insulin responsiveness in the High steers would also increase glycogenesis in the muscle, aligning with the glycogen results. The effect of selection for muscling on adrenaline responsiveness was measured using 7 adrenaline challenges ranging between 0.2 to 3.0 μg/kg liveweight. Plasma was analysed for NEFA, lactate, glucose and growth hormone concentration and area under curve (AUC) over time was calculated to reflect the tissue responses to adrenaline. The High steers had 30% lower lactate AUC than the Low steers at challenges greater than 2 μg/kg live weight, indicating lower muscle responsiveness at the highest adrenaline doses causing less glycogenolysis. This result also aligns with these animals having more muscle glycogen, thus more muscular animals may reduce the incidence of dark, firm, dry meat that is caused by low levels of glycogen at slaughter. At all levels of adrenaline challenge the High steers had at least 30% greater NEFA AUC, indicating that their adipose tissue was more responsive to adrenaline, resulting in greater lipolysis. In agreement with this response, the High steers had a higher plasma growth hormone concentration, which is likely to have contributed to the increased lipolysis evident in these animals in response to adrenaline. This difference in lipolysis may in part explain the reduced fatness of muscular cattle. There was no effect of selection for muscling on liver responsiveness to adrenaline. Contrary to our initial hypotheses, the High steers had less glycolytic type IIX myofibres in the LTL and larger average cross-sectional area of myofibres in the SM and ST than their Low muscled counterparts. This suggests that myofibre hypertrophy may be a possible mechanism leading to greater muscle mass of these High muscled animals. This also indicates that breeding for more muscular cattle can actually maintain the oxidative capacity of the muscle, a finding supported by the enzymatic results showing that the High muscled steers had lower activity of lactate dehydrogenase and higher activity of citrate synthase and isocitrate dehydrogenase. The High muscled cattle also had a higher concentration of iron in the LTL, and selection for increased muscling had no impact on pH decline or retail colour stability, factors which both affect meat quality. The aim of the second experiment was to determine if phenotypic measurements taken at the time of grading for Meat Standards Australia (MSA) could explain variance in ultimate pH (pHu) of carcasses and the probability of a carcass complying with MSA standards for pHu (≤5.7). Analyses of 204,072 carcass records collated by MSA at a Western Australian processor confirmed that more muscular cattle have a higher compliance rate for pHu. An increase in eye muscle area from 40 to 80 cm2, increased pHu compliance by approximately 14%. Therefore animals with greater muscularity had a lower incidence of dark, firm, dry beef supporting the results that High muscled cattle have increased insulin responsiveness, and reduced adrenaline responsiveness, leading to increased glycogen storage at slaughter. Thus, breeding more muscular cattle with eye muscle area greater than 70 cm2 may help alleviate the problem of dark, firm, dry beef. As rib fat depth increased from 0 to 20mm, pHu compliance increased by around 10%. Heavier cattle also had higher compliance than lighter cattle, and younger cattle also had higher compliance rates. This highlights the importance of good nutrition and high muscle glycogen storage prior to slaughter to maximise compliance rates. The final study examined 81 commercially managed High and Low muscled steers and showed that the effects of muscularity on muscle glycogen were variable as pasture quality and availability changed however there were no negative effects of selection for greater muscling on muscle glycogen, glycogenolysis pre-slaughter, or on the incidence of dark, firm and dry carcasses. Animal temperament assessed using crush score and flight speed measurements did however affect muscle glycogen with the more flighty animals having lower muscle glycogen concentrations

Investigating the factors contributing to dark cutting in Australian Grain Fed Cattle - Dataset

A compilation of industry stakeholder data for the production and grading of grain-fed beef cattle across southern QLD and northern NSW.&#13; &#13; Contains 6 year retrospective MSA carcass grading data. 2011-2017. Compiled as cattle lot group data with