An across breed, diet and tissue analysis reveals the transcription factor NR1H3 as a key mediator of residual feed intake in beef cattle.

BACKGROUND: Provision of feed is a major determinant of overall profitability in beef production systems, accounting for up to 75% of the variable costs. Thus, improving cattle feed efficiency, by way of determining the underlying genomic control and subsequently selecting for feed efficient cattle, provides a method through which feed input costs may be reduced. The objective of this study was to undertake gene co-expression network analysis using RNA-Sequence data generated from Longissimus dorsi and liver tissue samples collected from steers of two contrasting breeds (Charolais and Holstein-Friesian) divergent for residual feed intake (RFI), across two consecutive distinct dietary phases (zero-grazed grass and high-concentrate). Categories including differentially expressed genes (DEGs) based on the contrasts of RFI phenotype, breed and dietary source, as well as key transcription factors and proteins secreted in plasma were utilised as nodes of the gene co-expression network. RESULTS: Of the 2,929 DEGs within the network analysis, 1,604 were reported to have statistically significant correlations (≥ 0.80), resulting in a total of 43,876 significant connections between genes. Pathway analysis of clusters of co-expressed genes revealed enrichment of processes related to lipid metabolism (fatty acid biosynthesis, fatty acid ß-oxidation, cholesterol biosynthesis), immune function, (complement cascade, coagulation system, acute phase response signalling), and energy production (oxidative phosphorylation, mitochondrial L-carnitine shuttle pathway) based on genes related to RFI, breed and dietary source contrasts. CONCLUSIONS: Although similar biological processes were evident across the three factors examined, no one gene node was evident across RFI, breed and diet contrasts in both liver and muscle tissues. However within the liver tissue, the IRX4, NR1H3, HOXA13 and ZNF648 gene nodes, which all encode transcription factors displayed significant connections across the RFI, diet and breed comparisons, indicating a role for these transcription factors towards the RFI phenotype irrespective of diet and breed. Moreover, the NR1H3 gene encodes a protein secreted into plasma from the hepatocytes of the liver, highlighting the potential for this gene to be explored as a robust biomarker for the RFI trait in beef cattle.

Incidence, Predictors, and Outcomes of Cardiac Perforation During Pediatric Cardiac Catheterization: a Retrospective Observational Study from the Congenital Cardiac Interventional Study Consortium (CCISC).

INTRODUCTION: Cardiac perforation is a rare life-threatening complication of cardiac catheterization. There is very little published literature detailing risk factors for cardiac perforation and outcomes from this complication in children. MATERIALS AND METHODS: This was a retrospective study analyzing the cardiac catheterization case registry of the Congenital Cardiovascular Interventional Study Consortium. Children aged < 18 years were included during the study period of 9 years (January 2009-December 2017). The primary outcome measures were incidence of cardiac perforation, risk factors for and outcomes of patients who experience cardiac perforation during cardiac catheterization. RESULTS: Cardiac perforation occurred in 50 patients from a total of 36,986 (0.14%). Cardiac perforation was more likely to occur in younger, smaller patients undergoing urgent/emergent and interventional procedures (p < 0.01). Cardiac peroration risk was significantly different across diagnostic and procedure categories (p < 0.01). Higher CRISP score (Area Under Curve [AUC] = 0.87), lower age, and procedure category (radiofrequency perforation of pulmonary valve, AUC = 0.84) were independent predictors of cardiac perforation. Cardiac perforation was associated with a significantly higher rate of mortality (14%), further emergency procedure (42%), ECMO (14%), and cardiac arrest (6%), p < 0.01. CONCLUSIONS: Cardiac perforation during cardiac catheterization is a life-threatening complication with a range of associated secondary complications. Higher CRISP score, lower age, and radiofrequency perforation of pulmonary valve are independent predictors.

Evolution in the management of aorta to left ventricular tunnel in a national congenital cardiology centre.

An aorto-ventricular tunnel is a rare congenital cardiac defect, where a channel connects the lumen of the ascending aorta to the left or right ventricle. Four patients presented with an aorto-left ventricular tunnel over two decades at a median age of 8 months (range 0.1-10 months). Two patients (50%) had associated cardiac anomalies including hypoplastic left heart syndrome and left ventricular noncompaction/hypertrophic cardiomyopathy with aortic/pulmonary valve dysplasia in one patient each. Although traditionally surgical treatment has addressed this problem, management has evolved to transcatheter closure with excellent outcomes in appropriately selected patients at our national centre.

Identification of sperm proteins as biomarkers of field fertility in Holstein-Friesian bulls used for artificial insemination.

Despite passing stringent quality control, bulls used in artificial insemination can vary significantly in their fertility, emphasizing the need for reliable markers of sperm quality. This study aimed to identify sperm proteins acting as biomarkers of fertility in 2 different populations of dairy bulls classified based on their field fertility. Semen was collected and cryopreserved from: 54 Holstein bulls located in Ireland, classified according to fertility indexes as low fertility (LF, n = 23), medium fertility (n = 14), or high fertility (HF, n = 17); and 18 Holstein bulls located in Denmark, classified as LF (n = 8) or HF (n = 10). The proteome was measured through liquid chromatography-mass spectrometry and data were analyzed with the R software. Differentially abundant proteins between HF and LF bulls and biomarker proteins were determined through a modified t-test and random forest, respectively, selecting 301 differentially abundant proteins and 34 biomarker proteins. The predictive ability of the 34 biomarkers was evaluated employing support vector machine as the classifier, using their abundance levels in the Irish bulls to train the model and in the Danish bulls for validation. The prediction accuracy was 94.4%, with only one HF bull misclassified, corresponding to the lowest fertility index bull in the HF group. The biomarkers more abundant in sperm of HF bulls enriched axoneme assembly and sperm motility (false discovery rate <0.05), according to functional analysis. In conclusion, a robust model coupled with the application of appropriate bioinformatic tools allowed the identification of functionally relevant sperm proteins predictive of the fertility of Holstein bulls used in artificial insemination.

Sire contribution to fertilization failure and early embryo survival in cattle.

Despite passing routine laboratory tests of semen quality, bulls used in artificial insemination (AI) exhibit a significant range in field fertility. The objective of this study was to determine whether subfertility in AI bulls is due to issues of sperm transport to the site of fertilization, fertilization failure, or failure of early embryo or conceptus development. In experiment 1, Holstein-Friesian bulls (3 high fertility, HF, and 3 low fertility, LF) were selected from the national population of AI bulls based on adjusted fertility scores from a minimum of 500 inseminations (HF: +4.37% and LF: -12.7%; mean = 0%). Superovulated beef heifers were blocked based on estimated number of follicles at the time of AI and inseminated with semen from HF or LF bulls (n = 3-4 heifers per bull; total 19 heifers). Following slaughter 7 d later, the number of corpora lutea was counted and the uteri were flushed. Recovered structures (oocytes/embryos) were classified according to developmental stage and stained with 4',6-diamidino-2-phenylindole to assess number of cells and accessory sperm. Overall recovery rate (total structures recovered/total corpora lutea) was 52.6% and was not different between groups. Mean (± standard error of the mean) number of embryos recovered per recipient was 8.7 ± 5.2 and 9.4 ± 5.5 for HF and LF, respectively. Overall fertilization rate of recovered structures was not different between groups. However, more embryos were at advanced stages of development (all blastocyst stages combined), reflected in a greater mean embryo cell number on d 7 for HF versus LF bulls. Number of accessory sperm was greater for embryos derived from HF than for LF bulls. The aim of experiment 2 was to evaluate the effect of sire fertility on survival of bovine embryos to d 15. Day 7 blastocysts were produced in vitro using semen from the same HF (n = 3) and LF (n = 3) bulls and transferred in groups of 5-10 to synchronized heifers (n = 7 heifers per bull; total 42 heifers). Conceptus recovery rate on d 15 was higher in HF (59.4%,) versus LF (45.0%). Mean length of recovered conceptuses for HF bulls was not affected by fertility status. In conclusion, while differences in field fertility among AI sires used in this study were not reflected in fertilization rate, differences in embryo quality were apparent as early as d 7. These differences likely contributed to the higher proportion of conceptuses surviving to d 15 in HF bulls.

Leadless Micra Pacemaker Use in the Pediatric Population: Device Implantation and Short-Term Outcomes.

The development of Leadless cardiac pacemakers avoids the inherent complications that may occur secondary to lead insertion. A large number of devices have been inserted in adult patients although data in pediatric patients are lacking. We aimed to assess our experience with the Leadless device in the pediatric population. We performed a retrospective study on all pediatric patients who underwent insertion of a Leadless pacemaker in our center. Data were collected for demographic, procedural, and outcome variables. Nine patients with a median (IQR) age and weight of 13 (12-14) years and 37 (31-50) kg, respectively, were enrolled. The median (IQR) procedural time was 62 (60-65) min with insertion thresholds of 0.5 (0.35-1) Volts at 0.24 ms. All devices were successfully inserted without complication. One device was replaced with a single-lead endocardial pacemaker at 1 year for increased thresholds. Leadless pacemaker device insertion is feasible in pediatric patients. Further studies and long-term follow-up are needed to ascertain device longevity and complication rates.

Commotio Cordis Caused During Hurling Game

A teenage boy had a cardiac arrest following a blow to the chest from a hurling ball (sliotar). Prompt resuscitation and automated external defibrillation enabled a full recovery. This is the first reported case of commotio cordis caused by a sliotar although it is described in other sports. Primary prevention of commotio cordis (CC) and secondary prevention of cardiac death are discussed.

Role of early life nutrition on regulating the hypothalamic­anterior pituitary­testicular axis of the bull

The objective of this study was to examine the effect of nutrition during the first 18 weeks of life on the physiological and transcriptional functionality of the hypothalamic (arcuate nucleus region), anterior pituitary and testes in Holstein­Friesian bull calves. Holstein­Friesian bull calves with a mean (±S.D.) age and bodyweight of 19 (±8.2) days and 47.5 (±5.3) kg, respectively, were assigned to either a HIGH (n = 10) or LOW (n = 10) plane of nutrition, to achieve an overall target growth rate of 1.2 or 0.5 kg/day, respectively. At 126 ± 1.1 days of age, all calves were euthanised. Animal performance (weekly) and systemic concentrations of metabolic (monthly) and reproductive hormones (fortnightly) were assessed. Testicular histology, targeted gene and protein expression of the arcuate nucleus region, anterior pituitary and testes were also assessed using qPCR and immunohistochemistry, respectively. The expression of candidate genes in testicular tissue from post pubertal 19-month-old Holstein­Friesian bulls (n = 10) was compared to that of the 18-week-old calves. Metabolite and metabolic hormone profiles generally reflected the improved metabolic status of the calves on the HIGH (P< 0.001). Calves offered a HIGH plane of nutrition were heavier at slaughter (P < 0.001), had larger testes (P < 0.001), larger seminiferous tubule diameter (P < 0.001), more mature spermatogenic cells (P < 0.001) and more Sertoli cells (P < 0.05) in accordance with both morphological and transcriptional data. Overall, testicular gene expression profiles suggested a more mature stage of development in HIGH compared with LOW and were more closely aligned to that of mature bulls. Ghrelin receptor was the only differentially expressed gene between LOW and HIGH calves in either the anterior pituitary (P < 0.05) or arcuate nucleus region of the hypothalamus (P < 0.10) and was upregulated in LOW for both tissues. This study indicates that an enhanced plane of nutrition during early calfhood favourably alters the biochemical regulation of the hypothalamus­anterior pituitary­testicular axis, advancing testicular development and hastening spermatogenesis.

Plane of nutrition before and after 6 months of age in Holstein-Friesian bulls: I. Effects on performance, body composition, age at puberty, and postpubertal semen production.

The aim of this study was to examine the effect of plane of nutrition (1) during the first 6 mo of life and (2) from 6 mo of age to puberty on early growth characteristics, age at puberty, and postpubertal semen production in Holstein-Friesian bulls. Holstein-Friesian bull calves (n = 83) with a mean (standard deviation) age and body weight of 17 (4.4) d and 52 (6.2) kg, respectively, were assigned to a high (Hi) or low (Lo) plane of nutrition for the first 6 mo of life. The Hi and Lo calves received 1,200 and 450 g of milk replacer, respectively; Hi calves were fed concentrate ad libitum and Lo were fed a maximum of 1 kg concentrate daily, and concentrate allowances remained the same after weaning. At 24 wk of age, bulls were reassigned within treatment to either remain on the same diet or to switch to the opposite diet until puberty, resulting in 4 treatment groups: Hi-Hi, Hi-Lo, Lo-Lo, and Lo-Hi. After puberty, all bulls were fed a moderate plane of nutrition until 60 wk of age; thereafter, the diet was ad libitum concentrates until slaughter at 72 wk of age. Bulls were weighed weekly before weaning and every 2 wk after weaning. Scrotal circumference (SC) was measured every 2 wk, beginning at 15 wk of age. Beginning at a SC of 24 cm, electro-ejaculation was carried out every 2 wk to establish the onset of puberty. Semen collection continued monthly after puberty. Thermal images of the scrotum were taken monthly from 28 to 36 wk of age. Scrotal skin thickness (SST) was measured monthly (from 16 wk of age to puberty) using a digital calipers. Bulls on the Hi diet had a higher scrotal temperature and SST at each time point than those on the Lo diet. Average daily gain (ADG) was greatest in Hi-Hi bulls, with Hi-Lo and Lo-Hi having similar ADG but both being greater than Lo-Lo. Bulls on the Hi diet pre-6 mo of age were younger at puberty, regardless of diet offered post-6 mo of age. Bulls offered a Hi diet post-6 mo were heavier at puberty. Neither scrotal temperature nor dietary treatment affected postpubertal semen production variables. In conclusion, a high plane of nutrition during the first 6 mo of age hastened the onset of puberty and the availability of saleable semen, regardless of plane of nutrition post-6 mo of age.

Plane of nutrition before and after 6 months of age in Holstein-Friesian bulls: II. Effects on metabolic and reproductive endocrinology and identification of physiological markers of puberty and sexual maturation.

The aim of this study was (1) to examine the effect of plane of nutrition during the first and second 6 mo of life on systemic concentrations of reproductive hormones and metabolites in Holstein-Friesian dairy bulls, and (2) to establish relationships with age at puberty and postpubertal semen production potential. Holstein-Friesian bull calves (n = 83) with a mean (standard deviation) age and body weight of 17 (4.4) d and 52 (6.2) kg, respectively, were assigned to a high or low plane of nutrition for the first 6 mo of life. At 24 wk of age, bulls were reassigned, within treatment, either to remain on the same diet or to switch to the opposite diet until puberty, resulting in 4 treatment groups: high-high, high-low, low-low, and low-high. Monthly blood samples were analyzed for metabolites (albumin, urea, total protein, ß-hydroxybutyrate, glucose, nonesterified fatty acid, triglycerides and creatinine), insulin, insulin-like growth factor-1, leptin, adiponectin, FSH, and testosterone. A GnRH challenge was carried out at 16 and 32 wk of age (n = 9 bulls per treatment). Blood was collected at 15-min intervals for 165 min, with GnRH administered (0.05 mg/kg of body weight, i.v.) immediately after the third blood sample. Blood samples were subsequently analyzed for LH, FSH, and testosterone. Stepwise regression was used to detect growth and blood measurements to identify putative predictors of age at puberty and subsequent semen quality traits. Metabolic hormones and metabolites, in general, reflected metabolic status of bulls. Although FSH was unaffected by diet, it decreased with age both in monthly samples and following GnRH administration. Testosterone was greater in bulls on the high diet before and after 6 mo of age. Testosterone concentrations increased dramatically after 6 mo of age. Luteinizing hormone was unaffected by diet following GnRH administration but basal serum LH was greater in bulls on a high diet before 6 mo of age. In conclusion, the plane of nutrition offered before 6 mo of age influenced metabolic profiles, which are important for promoting GnRH pulsatility, in young bulls.

The economic burden of physical inactivity: a global analysis of major non-communicable diseases.

BACKGROUND: The pandemic of physical inactivity is associated with a range of chronic diseases and early deaths. Despite the well documented disease burden, the economic burden of physical inactivity remains unquantified at the global level. A better understanding of the economic burden could help to inform resource prioritisation and motivate efforts to increase levels of physical activity worldwide. METHODS: Direct health-care costs, productivity losses, and disability-adjusted life-years (DALYs) attributable to physical inactivity were estimated with standardised methods and the best data available for 142 countries, representing 93·2% of the world's population. Direct health-care costs and DALYs were estimated for coronary heart disease, stroke, type 2 diabetes, breast cancer, and colon cancer attributable to physical inactivity. Productivity losses were estimated with a friction cost approach for physical inactivity related mortality. Analyses were based on national physical inactivity prevalence from available countries, and adjusted population attributable fractions (PAFs) associated with physical inactivity for each disease outcome and all-cause mortality. FINDINGS: Conservatively estimated, physical inactivity cost health-care systems international $ (INT$) 53·8 billion worldwide in 2013, of which $31·2 billion was paid by the public sector, $12·9 billion by the private sector, and $9·7 billion by households. In addition, physical inactivity related deaths contribute to $13·7 billion in productivity losses, and physical inactivity was responsible for 13·4 million DALYs worldwide. High-income countries bear a larger proportion of economic burden (80·8% of health-care costs and 60·4% of indirect costs), whereas low-income and middle-income countries have a larger proportion of the disease burden (75·0% of DALYs). Sensitivity analyses based on less conservative assumptions led to much higher estimates. INTERPRETATION: In addition to morbidity and premature mortality, physical inactivity is responsible for a substantial economic burden. This paper provides further justification to prioritise promotion of regular physical activity worldwide as part of a comprehensive strategy to reduce non-communicable diseases. FUNDING: None.

Are cardiovascular disease risk assessment and management programmes cost effective? A systematic review of the evidence.

The World Health Organization recommends that countries implement population-wide cardiovascular disease (CVD) risk assessment and management programmes. The aim of this study was to conduct a systematic review to evaluate whether this recommendation is supported by cost-effectiveness evidence. Published economic evaluations were identified via electronic medical and social science databases (including Medline, Web of Science, and the NHS Economic Evaluation Database) from inception to March 2016. Study quality was evaluated using a modified version of the Consolidated Health Economic Evaluation Reporting Standards. Fourteen economic evaluations were included: five studies based on randomised controlled trials, seven studies based on observational studies and two studies using hypothetical modelling synthesizing secondary data. Trial based studies measured CVD risk factor changes over 1 to 3years, with modelled projections of longer term events. Programmes were either not, or only, cost-effective under non-verified assumptions such as sustained risk factor changes. Most observational and hypothetical studies suggested programmes were likely to be cost-effective; however, study deigns are subject to bias and subsequent empirical evidence has contradicted key assumptions. No studies assessed impacts on inequalities. In conclusion, recommendations for population-wide risk assessment and management programmes lack a robust, real world, evidence basis. Given implementation is resource intensive there is a need for robust economic evaluation, ideally conducted alongside trials, to assess cost effectiveness. Further, the efficiency and equity impact of different delivery models should be investigated, and also the combination of targeted screening with whole population interventions recognising that there multiple approaches to prevention.

Early onset of puberty in cattle: implications for gamete quality and embryo survival.

Advancing the age at which puberty and subsequent sexual maturation is attained in cattle is central to the reproductive and economic efficiency of both beef and dairy production systems worldwide. Onset of puberty in both male and female cattle is regulated by a complex network of biochemical processes and involves interaction among many key metabolic, neuroendocrine and reproductive tissues. Although our understanding of the biochemical interplay that conditions and eventually triggers the pubertal process has improved in recent years, much of the intricate mechanistic detail still eludes us. Environmental factors, such as nutritional management, as well as the genetic makeup of the animal undoubtedly affect the timing of puberty in cattle. In particular, there is now overwhelming evidence to support the importance of early life nutrition in regulating the timing of puberty in both bulls and heifers. For both genders, there is significant evidence that an improved metabolic status, early in calfhood, advances maturation of the hypothalamic-pituitary-gonadal axis, therefore facilitating earlier sexual development. Although advancing sexual maturation is a desirable goal, it is important that any strategy used does not impinge upon normal gametogenesis or postpubertal fertility potential. To this end, the aim of this review is to discuss the underlying biology of puberty in cattle with particular emphasis on the role of nutritional management during early calfhood in: (1) advancing the maturity of the hypothalamic-pituitary-gonadal axis; and (2) implications for the quality of gametes and subsequent fertility.

The economic burden of physical inactivity: a systematic review and critical appraisal.

OBJECTIVE: To summarise the literature on the economic burden of physical inactivity in populations, with emphases on appraising the methodologies and providing recommendations for future studies. DESIGN: Systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO registration number CRD42016047705). DATA SOURCES: Electronic databases for peer-reviewed and grey literature were systematically searched, followed by reference searching and consultation with experts. ELIGIBILITY CRITERIA: Studies that examined the economic consequences of physical inactivity in a population/population-based sample, with clearly stated methodologies and at least an abstract/summary written in English. RESULTS: Of the 40 eligible studies, 27 focused on direct healthcare costs only, 13 also estimated indirect costs and one study additionally estimated household costs. For direct costs, 23 studies used a population attributable fraction (PAF) approach with estimated healthcare costs attributable to physical inactivity ranging from 0.3% to 4.6% of national healthcare expenditure; 17 studies used an econometric approach, which tended to yield higher estimates than those using a PAF approach. For indirect costs, 10 studies used a human capital approach, two used a friction cost approach and one used a value of a statistical life approach. Overall, estimates varied substantially, even within the same country, depending on analytical approaches, time frame and other methodological considerations. CONCLUSION: Estimating the economic burden of physical inactivity is an area of increasing importance that requires further development. There is a marked lack of consistency in methodological approaches and transparency of reporting. Future studies could benefit from cross-disciplinary collaborations involving economists and physical activity experts, taking a societal perspective and following best practices in conducting and reporting analysis, including accounting for potential confounding, reverse causality and comorbidity, applying discounting and sensitivity analysis, and reporting assumptions, limitations and justifications for approaches taken. We have adapted the Consolidated Health Economic Evaluation Reporting Standards checklist as a guide for future estimates of the economic burden of physical inactivity and other risk factors.

Dilated cardiomyopathy secondary to vitamin D deficiency and hypocalcaemia in the Irish paediatric population: A case report.

We identified three infants with dilated cardiomyopathy (DCM) secondary to severe vitamin D deficieny and hypocalcaemia. All infants were exclusively breast fed, from dark skinned ethnic backgrounds, born and living in Ireland. None of these pregnant mothers or infants received the recommended vitamin D supplementation. Each infant presented in heart failure and required inotropic support as well as calcium and vitamin D replacement. Cardiac function subsequently improved. This highlights the public health issue that many high risk pregnant mothers and infants are not receiving the recommended vitamin D supplementation.

Doing it hard in the bush: Aligning what gets measured with what matters.

What gets measured gets managed. Funding of health services is substantially determined by operational activity and specific outcome indicators. In day-to-day clinical decision-making, surrogate markers, such as glycosylated haemoglobin and blood pressure, are commonly used to modify risks of 'hard' outcomes that include kidney failure, ischaemic cardiac events, stroke and all-cause mortality. In many settings, surrogates are all we have to go on. As a consequence, current health funding models heavily rely on surrogate-based key performance indicators [KPIs]. While surrogates are convenient and provide immediate information, there is an obligation to ensure that they are appropriate, reliable and validated in context. In contrast, hard outcomes, the real consequences of illness, are usually realised over an extended timeframe. Additionally, and for a host of reasons, hard endpoints have the greatest social, emotional and economic impact for people at the far end of the health system; those in rural and remote settings - 'in the bush' - especially Indigenous Australians. We propose a health service assessment approach that aligns short-term decision-making with patient-centred and longer term hard outcomes, one that takes into account community, cultural and environmental factors, especially remoteness. Communities should have a major say in determining what health indicators are measured and managed.

Pregnancy losses in cattle: potential for improvement.

For heifers, beef and moderate-yielding dairy cows, it appears that the fertilisation rate generally lies between 90% and 100%. For high-producing dairy cows, there is a less substantive body of literature, but it would appear that the fertilisation rate is somewhat lower and possibly more variable. In cattle, the major component of embryo loss occurs in the first 16 days following breeding (Day 0), with emerging evidence of greater losses before Day 8 in high-producing dairy cows. In cattle, late embryo mortality causes serious economic losses because it is often recognised too late to rebreed females. Systemic concentrations of progesterone during both the cycle preceding and following insemination affect embryo survival, with evidence of either excessive or insufficient concentrations being negatively associated with survival rate. The application of direct progesterone supplementation or treatments to increase endogenous output of progesterone to increase embryo survival cannot be recommended at this time. Energy balance and dry matter intake during the first 4 weeks after calving are critically important in determining pregnancies per AI when cows are inseminated at 70-100 days after calving. Level of concentrate supplementation of cows at pasture during the breeding period has minimal effects on conception rates, although sudden reductions in dietary intake should be avoided. For all systems of milk production, more balanced breeding strategies with greater emphasis on fertility and feed intake and/or energy must be developed. There is genetic variability within the Holstein breed for fertility traits, which can be exploited. Genomic technology will not only provide scientists with an improved understanding of the underlying biological processes involved in fertilisation and the establishment of pregnancy, but also, in the future, could identify genes responsible for improved embryo survival. Such information could be incorporated into breeding objectives in order to increase the rate of genetic progress for embryo survival. In addition, there is a range of easily adoptable management factors, under producer control, that can either directly increase embryo survival or ameliorate the consequences of low embryo survival rates. The correction of minor deficits in several areas can have a substantial cumulative positive effect on herd reproductive performance.

Fertility and genomics: comparison of gene expression in contrasting reproductive tissues of female cattle.

To compare gene expression among bovine tissues, large bovine RNA-seq datasets were used, comprising 280 samples from 10 different bovine tissues (uterine endometrium, granulosa cells, theca cells, cervix, embryos, leucocytes, liver, hypothalamus, pituitary, muscle) and generating 260 Gbases of data. Twin approaches were used: an information-theoretic analysis of the existing annotated transcriptome to identify the most tissue-specific genes and a de-novo transcriptome annotation to evaluate general features of the transcription landscape. Expression was detected for 97% of the Ensembl transcriptome with at least one read in one sample and between 28% and 66% at a level of 10 tags per million (TPM) or greater in individual tissues. Over 95% of genes exhibited some level of tissue-specific gene expression. This was mostly due to different levels of expression in different tissues rather than exclusive expression in a single tissue. Less than 1% of annotated genes exhibited a highly restricted tissue-specific expression profile and approximately 2% exhibited classic housekeeping profiles. In conclusion, it is the combined effects of the variable expression of large numbers of genes (73%-93% of the genome) and the specific expression of a small number of genes (<1% of the transcriptome) that contribute to determining the outcome of the function of individual tissues.

Efficacy of brief behavioral counselling by allied health professionals to promote physical activity in people with peripheral arterial disease (BIPP): study protocol for a multi-center randomized controlled trial.

BACKGROUND: Physical activity is recommended for people with peripheral arterial disease (PAD), and can improve walking capacity and quality of life; and reduce pain, requirement for surgery and cardiovascular events. This trial will assess the efficacy of a brief behavioral counselling intervention delivered by allied health professionals to improve physical activity in people with PAD. METHODS: This is a multi-center randomised controlled trial in four cities across Australia. Participants (N = 200) will be recruited from specialist vascular clinics, general practitioners and research databases and randomised to either the control or intervention group. Both groups will receive usual medical care, a written PAD management information sheet including advice to walk, and four individualised contacts from a protocol-trained allied health professional over 3 months (weeks 1, 2, 6, 12). The control group will receive four 15-min telephone calls with general discussion about PAD symptoms and health and wellbeing. The intervention group will receive behavioral counselling via two 1-h face-to-face sessions and two 15-min telephone calls. The counselling is based on the 5A framework and will promote interval walking for 3 × 40 min/week. Assessments will be conducted at baseline, and 4, 12 and 24 months by staff blinded to participant allocation. Objectively assessed outcomes include physical activity (primary), sedentary behavior, lower limb body function, walking capacity, cardiorespiratory fitness, event-based claudication index, vascular interventions, clinical events, cardiovascular function, circulating markers, and anthropometric measures. Self-reported outcomes include physical activity and sedentary behavior, walking ability, pain severity, and health-related quality of life. Data will be analysed using an intention-to-treat approach. An economic evaluation will assess whether embedding the intervention into routine care would likely be value for money. A cost-effectiveness analysis will estimate change in cost per change in activity indicators due to the intervention, and a cost-utility analysis will assess change in cost per quality-adjusted life year. A full uncertainty analysis will be undertaken, including a value of information analysis, to evaluate the economic case for further research. DISCUSSION: This trial will evaluate the efficacy and cost-effectiveness of a brief behavioral counselling intervention for a common cardiovascular disease with significant burden. TRIAL REGISTRATION: ACTRN 12614000592640 Australian New Zealand Clinical Trials Registry. Registration Date 4 June 2014.