Effects of reseeding with perennial ryegrass, chicory or tyfon in pure stands or mixtures on lamb performance postweaning.

Many producers reseed old pasture (OP) with the objective of improving lamb performance. Old pasture was reseeded with perennial ryegrass plus white clover (RGC), RGC plus chicory (CG), RGC plus tyfon (TG), chicory (C), or tyfon (T) to generate five treatments. In addition, a contiguous block of OP was included in the study for comparative purposes. Lambs (n = 286) were assigned to one of the five treatments plus the section of OP from just after weaning until slaughter. Grazing commenced 45 days after the desiccation of OP for reseeding. All lambs were managed by rotational grazing and drafted for slaughter at a specified target BW. No concentrate supplement was offered during the study. For the RGC, CG, TG, C and T treatments and the OP section, the average herbage NDF concentrations were 524, 473, 402, 352, 256 and 565 (SE 15.4) g/kg DM; total grazing days were 5 213, 4 005, 4 466, 2 262, 3 496 and 3 677 (SE 629.3); BW gain to slaughter was 211, 175, 205, 211, 199 and 203 (SE 9.5) g/day; days to slaughter were 91, 100, 84, 86, 78 and 88 (SE 4.8). Compared to RGC, the C, T, CG and TG treatments had lower herbage NDF concentrations (P < 0.05), and there was no difference (P > 0.05) for BW gain or days to slaughter. Chicory yielded significantly fewer (P < 0.05) grazing days, but tended to give a higher (P < 0.06) carcass weight than RGC. It is concluded that neither reseeding OP with RGC, including either C or T with RGC as a multispecies sward, nor growing pure stands of C or T increased (P < 0.05) lamb BW gain from weaning to slaughter or reduced days to slaughter.

Effects of joining at 7 months, and ewe genotype, on the performance of ewes to 19 months of age and that of their progeny to slaughter.

Two ways of reducing the cost of replacements are increasing litter size and number of litters produced; thus, the total weight of lamb carcass output per ewe lifetime. The effects of ewe genotype on the performance of ewes lambing at 1 year and of their progeny to slaughter, and the effect of age at first joining (7 or 19 months) on BW at ~19 months and survival to joining at 19 months were evaluated over two consecutive years, using 460 ewe lambs from three genotypes: Belclare (Bel), Suffolk × Belclare (Suf × Bel) and ≥ 75% Suffolk ancestry (Suf75). Lambs from the three genotypes were at a similar proportion of mature BW and half of the lambs, within genotype, were allocated to be joined for the first time at 7 or 19 months. The ewe lambs were managed in a grass-based rotational-grazing system, except when housed from December to March on a grass silage-based diet. Belclare ewes had larger litters (P < 0.001), reared more lambs per ewe joined (P < 0.01), were lighter at lambing and at 19 months (P < 0.01), were of smaller body size at 19 months (P < 0.001) and their progeny were lighter at weaning (P < 0.05) relative to Suf75 genotype; the Suf × Bel ewes were intermediate for most traits but had a significantly lower litter size (P < 0.05) than Bel ewes. Progeny from Suf × Bel ewes were 17 days younger at slaughter (P < 0.01) relative to those from Bel ewes. Ewe genotype had no effect (P > 0.05) on lamb mortality (born dead, total mortality to weaning), lambing assistance, number of ewes that failed to lamb, or on ewe survival to 19 months of age. Increasing ewe BW at joining increased the probability (P < 0.001) of rearing at least one lamb and this effect was consistent across genotypes. There were significant relationships (P < 0.001) between ewe BW at lambing and lamb BW at birth and at weaning of 0.053 (SE 0.0089) kg and 0.29 (SE 0.049) kg, respectively. Ewes that lambed at 1 year were 2 kg lighter (P < 0.001) at 19 months of age and had a smaller body size (P < 0.01) relative to those not joined. It is concluded that ewe genotype had a significant effect on number of lambs reared, and thus lamb carcass output. Whilst lambing at 1 year reduced BW by 2 kg when joined at 19 months, it did not affect ewe survival to that stage.

Comparative Study of Dissolution for Cannabidiol in EU and US Hemp Oil Products by HPLC.

For the first time, a simple and robust HPLC method has been developed for dissolution studies for cannabidiol (CBD) in hemp oil products. An isocratic elution of samples performed on SOLAS™ C18 150 mm x 4.6 mm, 5 µm column with a mobile phase consisting of 75:25 acetonitrile-water v/v, delivered at a flow rate 1.5 mL/minutes to variable wavelength detector using 214 nm. An in-house validated assay test was executed for calculating the purity of hemp oil products and also for considering the dissolution medium to be used. For dissolution studies, equivalent of 5 mg and/or 10 mg of the active was introduced into 500 mL of simulated gastric and intestinal fluids separately, and dissolution was performed at 50 rpm using paddles for 180 min. Dissolution profiles for hemp oil products purchased from the United States and Europe were compared. Additionally, dissolution testing was conducted to study the effect of percentage CBD release on increased agitation speed of 75 and 100 rpm and also, on extended dissolution runtime of 240 min.

Effects of grass and maize silage feed value, offering soybean meal with maize silage, and concentrate feed level in late pregnancy, on ewe and lamb performance.

In many countries, daily herbage accumulation on pasture declines towards zero during the winter period; thus, many pregnant ewes are housed and offered conserved forages supplemented with concentrate prior to parturition. The effects of forage type and feed value (FV), offering soybean meal with maize silage during mid and late pregnancy, and concentrate feed level in late pregnancy on the performance of ewes and their progeny (to slaughter) were evaluated. Ewes (n = 151) were assigned to one of nine treatments from mid-pregnancy until lambing. Medium FV and high FV grass silages (metabolisable energy concentrations of 10.7 and 12.0 MJ/kg DM) were offered ad libitum supplemented with either 15 or 25 kg concentrate/ewe during late pregnancy. Low and high DM maize silages (starch concentrations of 80 and 315 g/kg DM) were offered ad libitum either alone or with soybean meal (200 g/d) and supplemented with 15 kg concentrate during late pregnancy. A final treatment consisted of high FV grass silage supplemented with 5 kg soybean/ewe over the final 4 weeks of pregnancy. Ewes and lambs were put to pasture in a rotational-grazing system within 3 days of lambing. There were no interactions (P > 0.05) between grass silage FV and concentrate feed level for ewe or lamb traits. Increasing grass silage FV increased food intake (P < 0.001) during late pregnancy, ewe BW and body condition score (BCS) at lambing (P < 0.001), lamb BW at birth (P < 0.001) and weaning (P < 0.05), and reduced age at slaughter (P = 0.06). Increasing concentrate feed level increased metabolisable energy (P < 0.05) intake during late pregnancy but had no effect (P > 0.05) on ewe or lamb performance. Increasing maize DM at harvest and offering soybean meal with maize silage increased food intake (P < 0.001) and ewe BW and BCS at lambing (P < 0.05 or P < 0.01). Offering soybean meal with maize silage increased lamb BW at birth (P < 0.01) and reduced age at slaughter (P < 0.05). Reducing supplementation of high FV grass silage to 5 kg of soybean meal had no effect (P > 0.05) on animal performance. Replacing grass silage with maize silage did not affect (P > 0.05) BW gain of lambs. It is concluded that increasing the FV of the grass silage offered during pregnancy had the greatest positive impact on ewe and lamb performance.

Cervical mucus sialic acid content determines the ability of frozen-thawed ram sperm to migrate through the cervix.

The aim of this study was to investigate the properties and to functionally characterize the cervical mucus that modulates sperm transport through the cervix by using ewe breeds with a divergent pregnancy rate (Belclare and Suffolk; high and low, respectively) following cervical insemination using frozen-thawed semen. Sperm number, as well as sialic acid and fucose content in both the channels and in the lumen of different regions of the cervix were quantified in inseminated Belclare and Suffolk ewes. Expression of glycosyltransferase and MUC genes, glycosidase activity and sialic acid speciation in follicular phase cervical tissue and mucus were assessed. More spermatozoa were found in the cervical channels in the region closest to the cervical os in Belclare than Suffolk ewes (P < 0.05) and Suffolk ewes had a higher sialic acid content in the cervical channels than Belclare ewes (P < 0.05) in all regions of cervix. Suffolk ewes had significantly higher expression of FUT1, ST6GAL1 and MUC5AC than Belclare ewes. There was no difference between the breeds in glycosidase activity (P > 0.05). Levels of Neu5Ac were higher in Belclare than Suffolk ewes (P < 0.05) and levels of Neu5Gc was higher in Suffolk than Belclare ewes (P < 0.05). Competitive sperm penetration assays demonstrated that frozen-thawed sperm progression increased when cervical mucus was incubated with sialyllactose prior to a sperm penetration test (P < 0.05). These results suggest that the difference between Belclare and Suffolk ewes in sperm transport with frozen-thawed semen is due to the higher concentration of sialic acid within channels, which binds to spermatozoa and reduces their ability to traverse the cervix.

Preoperative gastric residual volumes in fasted patients measured by bedside ultrasound: a prospective observational study.

The purpose of this prospective observational study was to measure gastric volumes in fasted patients using bedside gastric ultrasound. Patients presenting for non-emergency surgery underwent a gastric antrum assessment, using the two-diameter and free-trace methods to determine antral cross-sectional area (CSA). Gastric residual volume (GRV) was calculated using a validated formula. Univariate and multivariable analyses were performed to examine any potential relationships between 'at risk' GRVs (>100 ml) and patient factors. Two hundred and twenty-two successful scans were performed; of these 110 patients (49.5%) had an empty stomach, nine patients (4.1%) had a GRV >100 ml, and a further six patients (2.7%) had a GRV >1.5 ml/kg. There was no significant relationship between at risk GRV and obesity, diabetes mellitus, gastro-oesophageal reflux disease or opioid use, although our study had insufficient power to exclude an influence of one or more of these factors. Our results indicate that despite compliance with fasting guidelines, a small percentage of patients still have GRVs that pose a pulmonary aspiration risk. Anaesthetists should consider this background incidence when choosing anaesthesia techniques for their patients. While future observational studies are required to determine the role of preoperative bedside gastric ultrasound, it is possible that this technique may assist anaesthetists in identifying patients with 'at risk' GRVs.

An independent validation study of loci associated with nematode resistance in sheep.

Gastrointestinal nematode infection is a constraint on sheep production worldwide. Selective breeding programmes to enhance resistance to nematode infection are currently being implemented in a number of countries. Identification of loci associated with resistance to infection or causative mutations for resistance would enable more effective selection. Loci associated with indicator traits for nematode resistance has been identified in previous studies. In this study, Scottish Blackface, Texel and Suffolk lambs were used to validate the effects at eight genomic regions previously associated with nematode resistance (OAR3, 4, 5, 7, 12, 13, 14, 21). No SNP was significantly associated with nematode resistance at the region-wide level but seven SNPs in three of the regions (OAR4, 12, 14) were nominally associated with trichostrongyle egg count in this study and six of these were also significant when fitted as single SNP effects. Nematodirus egg count was nominally associated with SNPs on OAR3, 4, 7 and 12.

Plane of nutrition during the rearing phase for replacement ewes of four genotypes: II - effects on performance during first pregnancy and to weaning, and of their progeny.

Plane of nutrition (PN) offered to ewe replacements during the rearing phase (8 to 17 months) and first pregnancy may affect reproductive and progeny performance when replacements are joined at ~19 months. The effects of PN offered to spring-born ewe replacements during their first winter (winter_1), second summer (summer_2) and subsequent winter (mid and late pregnancy; winter_2) were evaluated, over 3 consecutive years, using 287 ewe lambs of four genotypes: Charmoise×Scottish Blackface (C×SBF), Belclare×SBF (Bel×SBF), Belclare (Bel) and Belclare×SBF (heterozygous for a gene, either FecGH or FecXG mutations, that increases ovulation rate: BelMG×SBF). Ewe lambs were offered, daily, a deferred-grazed herbage allowance (HA) of either 0.75 or 1.75 kg dry matter during winter_1. During summer_2 the replacements were set-stocked to maintain sward heights of 4 or 6 cm. Ewes were housed during mid and late pregnancy (winter_2) and offered either medium or high-feed-value grass silage, thus yielding a 2×2×2 factorial design. Increasing HA during winter_1 and residual sward height during summer_2 increased ewe BW post joining (P0.05) on number of lambs reared. Increasing HA during winter_1 increased lamb BW at birth (P<0.05) and reduced carcass fat score (P<0.05). There was a significant interaction between PN offered during winter_1 and summer_2 for average daily gain (ADG) from birth to 5 weeks (P<0.01) and from 5 to 10 weeks (P<0.05): progeny of replacements that experienced either a high or low PN throughout the rearing phase had lower ADG than lambs born to the replacements that experienced a low PN only during winter_1 or summer_2. Increasing PN during winter_2 increased ewe BW (P<0.001), lamb BW at birth (P<0.001) and weaning (P<0.05) and reduced the proportion of ewes that failed to lamb (P<0.01). Ewe genotype had a significant (P<0.001) effect on litter size (1.48 to 2.45), number of lambs reared, lamb BW at birth and weaning, lamb ADG and age at slaughter. It is concluded that, among the nutrition treatments examined, increasing PN during mid and late pregnancy had the greatest effect on ewe and progeny performance. Although increasing PN offered during winter_1 increased lamb birth BW, PN offered during summer_2 had no effect on lamb performance. There were no significant interactions between PN and ewe genotype.

Plane of nutrition during the rearing phase for replacement ewes of four genotypes: I - effects on growth and development, and on ovulation rate at first joining.

Plane of nutrition (PN) offered to ewe replacements during the rearing phase (8 to 17 months) affects BW at joining and may affect reproductive performance when joined at ~19 months. The effects of PN offered to ewe replacements during their first winter (winter_1) and second summer (summer_2) were evaluated over 3 consecutive years, using 287 spring-born ewe lambs, representing four genotypes (Belclare (Bel), Charmoise×Scottish Blackface (C×SBF), Bel×SBF (Bel×SBF), Bel×SBF that were heterozygous either FecGH or FecXG mutations that increase ovulation rate (OR) (BelMG×SBF)). During extended (deferred) grazing in winter_1 (November to March) the lambs were offered herbage DM allowances (HA) of 0.75 (L) or 1.75 (H) kg/day. During summer_2 (March to August) the replacements were set stocked to maintain sward heights of 4 (L) or 6 (H) cm, thus yielding a 2×2 factorial design for the nutrition treatments (71 to 73 animals/treatment). Increasing HA during winter_1, and residual sward height during summer_2, increased (P0.05) on OR. Mean BW at joining was 53.3, 56.8, 56.6 and 61.7 (SEM 0.74) kg for ewes offered the LL, LH, HL and HH treatments, respectively. Mean OR of C×SBF and BelMG×SBF differed (P<0.001) from that of Bel×SBF by -0.58 and +0.47, respectively. Correlations between linear measurements (LMs) of body size and BW at 7, 12 and 17 months were all positive and significant (P<0.001). The precision of the set of LMs as a predictor of BW at joining improved with age (R 2 0.46, 0.54 and 0.74 at 7, 12 and 17 months) but BW at a given age was a better predictor at all age time points. Chest girth was the best predictor, among the LMs, of BW at joining and its explanatory power increased with age. Equations developed using LMs at 7, 12 or 17 months, to predict BW at joining exhibited biases of -2.1, -1.5 and +0.9 kg, respectively. It is concluded that whilst altering PN during the rearing phase changed BW by 16% it had no effect on OR. There was no interaction (P>0.05) between the PN offered during winter_1 and summer_2, or PN and ewe genotype for BW at joining or OR. LMs, either at 7, 12 or 17 months of age, are useful predictors of BW at joining.

Cobalt supplementation, alone or in combination with vitamin B and selenium: Effects on lamb performance and mineral status.

The effects of supplementing lambs with Co, either alone or in combination with vitamin B and Se, were evaluated over the period from weaning to selection for slaughter. Two hundred and five recently weaned (at 14 wk [SD 0.44] of age), spring-born lambs of various crossbred genotypes were stratified, within genotype, by BW and gender and allocated to 3 groups, which were then allocated at random to one of the following treatments: no supplement (Control), a supplement containing Co only (Co-only), or a supplement containing Co, vitamin B, and Se (VitMin). The concentration of Co in the Co-only supplement was 2.1 mg/mL (as cobalt sulfate); the VitMin supplement contained Co (10 mg/mL, as cobalt acetate), vitamin B (200 µg/mL), and Se (0.25 mg/mL, as sodium selenite). Lambs on the Co-only and VitMin treatments received, every 14 d, 10 and 2.1 mL, respectively, of oral drench. Lambs were managed in a rotational-grazing system from 12 July (swards predominantly ) and selected for slaughter, on the basis of BW, after 45, 73, or 115 d; all remaining lambs were slaughtered on d 157. Supplementation, with Co-only or VitMin, increased BW at slaughter ( < 0.01), ADG ( < 0.001), carcass weight ( < 0.001), dressing percentage ( < 0.001), carcass fat score ( < 0.05), and the proportion selected for slaughter by d 73 ( < 0.05) and 115 ( < 0.01). Relative to the Control, the benefit to ADG from supplementation increased as the season advanced. Therefore, supplementation did not alter ( = 0.82) ADG between d 1 and 45 but increased ADG over the intervals d 45 to 73 ( < 0.01), d 73 to 115 ( < 0.001), and d 115 to 157 ( < 0.001). There was no difference ( > 0.05) between the Co-only and the VitMin treatments for ADG, carcass weight, fat score, or dressing percentage. Supplementation with Co increased liver Co concentration ( < 0.001), and lambs supplemented with VitMin had greater liver Co concentration than lambs supplemented with Co-only ( < 0.05); the concentrations were 0.18, 0.85, and 1.18 µmol/L for the Control, Co-only, and VitMin treatments, respectively. Treatment had no effect ( = 0.65) on the concentration of Se in kidney tissue. It is concluded that supplementation with Co increased lamb performance after weaning, that response to supplementation increased as the grazing season progressed, and that no extra benefit in performance resulted from augmenting supplementary Co with B and Se.

Immunogenomics of gastrointestinal nematode infection in ruminants - breeding for resistance to produce food sustainably and safely.

Gastrointestinal nematode (GIN) infection of ruminants represents a major health and welfare challenge for livestock producers worldwide. The emergence of anthelmintic resistance in important GIN species and the associated animal welfare concerns have stimulated interest in the development of alternative and more sustainable strategies aimed at the effective management of the impact of GINs. These integrative strategies include selective breeding using genetic/genomic tools, grazing management, biological control, nutritional supplementation, vaccination and targeted selective treatment. In this review, the logic of selecting for "resistance" to GIN infection as opposed to "resilience" or "tolerance" is discussed. This is followed by a review of the potential application of immunogenomics to genetic selection for animals that have the capacity to withstand the impact of GIN infection. Advances in relevant genomic technologies are highlighted together with how these tools can be advanced to support the integration of immunogenomic information into ruminant breeding programmes.

Effects of shearing, forage type and feed value, concentrate feed level, and protein concentration on the performance of housed finishing lambs.

The effects of high and medium feed value grass silage or maize silage (MS), each offered with a range of concentrate feed levels, and ad libitum concentrate on the performance of finishing lambs, which were either shorn or unshorn, were evaluated. Three silages were used: 1 medium feed value (MFV) and 1 high feed value (HFV) grass silage (DM digestibility [DMD] of 71.3% and 74.5%, respectively) and 1 MS (DM and starch concentrations of 30.9% and 35.3% DM, respectively). The 3 silages were offered ad libitum with daily allowances of 0.4, 0.8, or 1.2 kg concentrate per lamb. Two additional treatments were: 1) MS supplemented with 0.4 kg of a low CP (LP) concentrate and 2) concentrate offered ad libitum with 0.5 kg/d of HFV grass silage. These 11 dietary treatments were offered to 264 crossbred Suffolk lambs (initial BW = 39.0 kg), half of which were unshorn and half of which were shorn, for a 54-d finishing period, resulting in 22 treatments. Shearing increased forage DMI (P < 0.001) but did not alter (P > 0.05) carcass weight, carcass gain, or ADG, and there was no interaction with dietary treatment. Reducing CP concentration of the concentrate offered with MS did not alter (P > 0.05) feed intake or lamb performance. Increasing concentrate feed level increased feed DMI and lamb performance (P < 0.001). The linear response in ADG to increased concentrate supplementation was greater (P = 0.012) for MFV than HFV grass silage, and a corresponding difference in carcass gain approached significance (P = 0.075). The linear response was greater for grass silage than for MS for ADG (P < 0.01) and carcass gain (P = 0.019). The response in lamb performance from increased concentrate supplementation was linear for HFV grass silage and MS but quadratic (P < 0.05) for the MFV grass silage, reflecting the large response for this silage when concentrate supplement was increased from 0.4 to 0.8 kg. Relative to the MFV grass silage supplemented with 0.8 kg concentrate, the potential concentrate-sparing effects of the HFV grass silage and MS were 0.16 and 0.32 kg concentrate per lamb daily, respectively. It is concluded that shearing lambs that are housed during finishing reduces the efficiency of the conversion of ME to carcass gain. Maize silage can replace HFV grass silage in the diet of finishing lambs. The total dietary protein concentration for finishing lambs can be reduced to 9% DM without adversely affecting carcass gain.

A genome-wide association study of bronchodilator response in asthmatics.

Reversibility of airway obstruction in response to ß2-agonists is highly variable among asthmatics, which is partially attributed to genetic factors. In a genome-wide association study of acute bronchodilator response (BDR) to inhaled albuterol, 534 290 single-nucleotide polymorphisms (SNPs) were tested in 403 white trios from the Childhood Asthma Management Program using five statistical models to determine the most robust genetic associations. The primary replication phase included 1397 polymorphisms in three asthma trials (pooled n=764). The second replication phase tested 13 SNPs in three additional asthma populations (n=241, n=215 and n=592). An intergenic SNP on chromosome 10, rs11252394, proximal to several excellent biological candidates, significantly replicated (P=1.98 × 10(-7)) in the primary replication trials. An intronic SNP (rs6988229) in the collagen (COL22A1) locus also provided strong replication signals (P=8.51 × 10(-6)). This study applied a robust approach for testing the genetic basis of BDR and identified novel loci associated with this drug response in asthmatics.

Effects of silage from maize crops differing in maturity at harvest, grass silage feed value and concentrate feed level on performance of finishing lambs.

The effects of (i) medium and high feed value (MFV and HFV) maize silages and (ii) MFV and HFV grass silages, each in combination with a range of concentrate feed levels, on the performance of finishing lambs were evaluated using 280 Suffolk-X lambs (initial live weight 36.1 kg). The MFV and HFV maize silages represented crops with dry matter (DM) concentrations of 185 and 250 g/kg, respectively, at harvest, and had starch and metabolisable energy (ME) concentrations of 33 and 277 g/kg DM and 9.6 and 11.0 MJ/kg, respectively. HFV and MFV grass silages had DM and ME concentrations of 216 and 294 g/kg and 11.0 and 11.5 MJ/kg DM, respectively. A total of 13 treatments were involved. The four silages were offered ad libitum with daily concentrate supplements of 0.2, 0.5 or 0.8 kg per lamb. A final treatment consisted of concentrate offered ad libitum with 0.5 kg of the HFV grass silage daily. Increasing the feed value of grass silage increased (P < 0.001) forage intake, daily carcass and live weight gains, final live weight and carcass weight. Increasing maize silage feed value tended to increase (P = 0.07) daily carcass gain. Increasing concentrate feed level increased total food and ME intakes, and live weight and carcass gains. There was a significant interaction between silage feed value and the response to concentrate feed level. Relative to the HFV grass silage, the positive linear response to increasing concentrate feed level was greater with lambs offered the MFV grass silage for daily live weight gain (P < 0.001), daily carcass gain (P < 0.01) and final carcass weight (P < 0.01). Relative to the HFV maize silage, there was a greater response to increasing concentrate feed level from lambs offered the MFV maize silage in terms of daily carcass gain (P < 0.05) and daily live weight gain (P = 0.06). Forage type had no significant effect on the response to increased concentrate feed level. Relative to the MFV grass silage supplemented with 0.2 kg concentrate, the potential concentrate-sparing effect of the HFV grass silage, and the MFV and HFV maize silages was 0.41, 0.09 and 0.25 kg daily per lamb, respectively. It is concluded that increasing forage feed value increased forage intake and animal performance, and maize silage can replace MFV grass silage in the diet of finishing lambs as performance was equal to or better (depending on maturity of maize at harvest) than that for MFV grass silage.

A polymorphism in the thyroid hormone receptor gene is associated with bronchodilator response in asthmatics.

A pro-asthmatic culture milieu and ß2-agonist (isoproterenol) were previously shown to regulate the expression of select transcription factors (TFs) within human airway epithelial and smooth muscle cells. This study tests 1116 single-nucleotide polymorphisms (SNPs) across 98 of these TF genes for association with bronchodilator response (BDR) in asthma patients. Genotyping was conducted using the Illumina HumanHap550v3 Beadchip in 403 non-Hispanic White asthmatic children and their parents. SNPs were evaluated for association with BDR using family and population-based analyses. Forty-two SNPs providing P-values <0.1 in both analyses were then genotyped in three adult asthma trials. One SNP 5' of the thyroid hormone receptor-ß gene was associated with BDR in the childhood population and two adult populations (P-value=0.0012). This investigation identified a novel locus for inter-individual variability in BDR and represents a translation of a cellular drug-response study to potential personalization of clinical asthma management.

Ewe breed differences in fertility after cervical AI with frozen-thawed semen and associated differences in sperm penetration and physicochemical properties of cervical mucus.

The objective of this study was to examine sperm penetration through cervical mucus and associated physicochemical properties of cervical mucus from Belclare and Suffolk ewes - two breeds with divergent pregnancy rate following cervical AI using frozen-thawed semen. In Experiment 1, sperm penetration through cervical mucus was assessed in 15 Belclare and 15 Suffolk ewes at 30, 48 and 57h post sponge removal. In Experiment 2, rheological properties of mucus from 17 Belclare and 19 Suffolk ewes at 48 and 57h post sponge removal were determined. In Experiment 3, 20 Belclare and 20 Suffolk ewes were used to assess mucus ferning and pH collected at 42, 48, 57 and 65h post sponge removal. In Experiment 1, a higher number of sperm penetrated cervical mucus from Belclare ewes at 48h, reflected by a breed by time interaction (P=0.05). In Experiment 2, mucus from Suffolk ewes tended to have higher elastic and complex moduli than that from Belclare ewes (P=0.06) regardless of time of collection. There was no effect of ewe breed on the viscous modulus. In Experiment 3, there was a significant effect of time post sponge removal on ferning (P<0.01), but there was no effect of breed. There was no effect of time or breed on mucus pH. It is concluded that breed differences in the rheological properties of cervical mucus affect the ability of sperm to swim through cervical mucus and this may explain breed differences in fertility observed after cervical AI using frozen-thawed semen.

A cumulative dose, safety and tolerability study of arformoterol in pediatric subjects with stable asthma.

PURPOSE: Short-acting ß(2) -agonists (SABAs) are recommended for treating acute pediatric asthma. The long-acting ß(2) -agonist (LABA) arformoterol is approved for the maintenance treatment of chronic obstructive pulmonary disease (COPD). Arformoterol acts rapidly, is delivered via nebulization, and, as such, raises concerns from the FDA over possible off-label use in acute asthma in children. As a step to investigate this issue, this study evaluated the safety and tolerability of three consecutive doses of arformoterol administered over 1 hr in children with stable asthma. METHODS: This study consisted of a double-blind, crossover period in which subjects (ages 2-11 years) with stable asthma were randomized to three consecutive nebulized doses of arformoterol (7.5 µg/dose) or levalbuterol (0.63 mg/dose) administered over 1-hr (0, 30, and 60 min) followed by an open-label period with three consecutive doses of arformoterol (15 µg/dose) administered over 1 hr. Endpoints were change in heart rate, blood pressure, and serum potassium and glucose levels. Other endpoints included adverse events and pulmonary function. RESULTS: There were no clinically important mean changes from pre-dose in heart rate, blood pressure, or serum glucose levels, across treatment groups. Substantial declines in serum potassium levels were observed both 2 and 6 hr post-dosing. Two subjects had declines to 2.8 mEq/L and 2.9 mEq/L 2-hr post-dosing. Adverse events were infrequent and differences in forced expiratory volume in 1 sec and peak expiratory flow across treatment groups were not clinically meaningful. CONCLUSION: In this study, in children with stable asthma, three consecutive doses of arformoterol (7.5 and 15 µg) and levalbuterol were overall well tolerated. Nonetheless, serum potassium levels demonstrated substantial mean declines after dosing. These findings do not address or support the safety and tolerability of arformoterol use in acute exacerbations of asthma in children.

In vitro assessment of sperm from bulls of high and low field fertility.

The aim of this study was to investigate the reasons for differences in field fertility of bulls following insemination with frozen-thawed semen. The study was carried out in two separate parts over two years and comparisons were made between 5 high and 4 low fertility Holstein Friesian bulls as determined by their either 90 day non-return rate (Year 1) or calving rate (Year 2). Two high fertility Limousin bulls were included in Year 1 for comparative purposes. The ability of sperm from each bull to penetrate artificial mucus was assessed (Year 1 = 7 replicates; Year 2 = 5 replicates). Glass capillary tubes (2 per bull per replicate) were filled with artificial mucus and incubated with sperm stained in 1% Hoechst 33342 for 30 min at 37 °C. The number of sperm were subsequently counted at 10 mm intervals along the tube between 40 and 80 mm markers. Sperm mitochondrial activity of each bull was assessed by the MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide) assay (4 replicates in each year). Sperm were incubated with MTT for 1 h at 37 °C following which the absorbance of formazan was read using a spectrophotometer. Sperm viability after thawing was assessed for each bull using a live/dead sperm viability kit (Year 1 = 3 replicates; Year 2 = 4 replicates). A minimum of 250 cells were assessed per bull in each replicate and classified as either live or dead. Finally, the ability of sperm to fertilize oocytes in vitro and their ability to develop to blastocyst stage embryos were assessed (5 replicates in each year involving 220 to 306 oocytes per bull). Data transformation to normalize residuals was required for mucus sperm penetration (square root) and IVF (cleavage and blastocyst rate) results (arcsin). The mean number of sperm counted at each 10 mm mark between 40 and 80 mm was higher in the high fertility (56.0; 95% CI 39.5 to 75.3) compared to the low fertility (42.9; 95% CI 29.3 to 59.1) Holstein Friesian bulls but the difference did not reach formal significance (P = 0.09). Fertility status had no effect on the ability of sperm to reduce MTT to formazan (mean absorbance 0.34 ± 0.051 and 0.30 ± 0.044) or on the percentage of live sperm per straw (mean 47.3 ± 5.47 and 32.4 ± 4.66) for high and low fertility Holstein Friesian bulls respectively. Oocyte cleavage rate following insemination with sperm from high fertility Holstein Friesian bulls was significantly higher than with sperm from low fertility Holstein Friesian bulls [76.7% (95% CI 60.9 to 89.4) and 55.3 (95% CI 40.4 to 69.7) respectively, P = 0.04]. There was no significant effect of bull fertility on blastocyst rate [34.7% (95% CI 21.1 to 49.6) and 24.2 % (95% CI 14.1 to 36.0) for the high and low fertility Holstein Friesian bulls, respectively; P = 0.2]. In conclusion, sperm from high fertility bulls tended to be more effective in penetrating artificial mucus and to have an increased ability to fertilize oocytes in vitro; however, once fertilization occurred subsequent embryo development was not significantly affected by fertility status.

Temporal studies on Fasciola hepatica in Galba truncatula in the west of Ireland.

The population dynamics and prevalence of Fasciola hepatica in Galba truncatula were investigated on the Teagasc hill sheep farm in Country Mayo, Ireland from August 2006 until March 2008. Galba truncatula (n=974) were collected at fortnightly intervals in 4 snail habitats on the farm, their relative density and mean monthly rainfall and temperature were recorded. Snail abundance was associated with rainfall and temperature. G. truncatula abundance was generally low during winter 2006/2007 (December 2006-February 2007), mid spring and summer 2007 (April-July) and late autumn and winter 2007/2008 (October 2007-February 2008). Overall, two peaks in G. truncatula abundance were evident during the study period, an early spring (March) and late summer/autumn (late August-October) peak. Seasonal differences were observed in the prevalence of F. hepatica in G. truncatula, the greatest prevalence was evident in 2007 during the summer (25%) and autumn (16%). Two seasonal transmission peaks, as evident by the presence of mature infections in snails, one in summer/autumn and the other in late winter/early spring. Not unsurprising, cercariae (28%) and rediae (29%) were the predominant developmental stages observed in mature and pre-adult snails respectively. Worthy of note in this study, cercariae were also evident in pre-adult snails. The present study highlights the influence of milder temperatures and wetter conditions on both snail and fluke development. If the trend in mild and wet weather conditions continues, there is the potential for an increase in the number of G. truncatula habitats and ultimately the prevalence of fasciolosis in grazing livestock in Ireland.

The safety and efficacy of arformoterol and formoterol in COPD.

This study evaluated the safety and efficacy of arformoterol and formoterol over 6-months in subjects with COPD. In a multi-center, 6-month randomized, double-blind, double-dummy trial, subjects with COPD (mean FEV(1) 1.21 L, approximately 41.0% predicted) were randomized to receive either nebulized arformoterol (15 microg BID [n = 149][ARF 15], 25 microg BID [n = 147][ARF 25]), or racemic formoterol (12 microg BID [n = 147][FORM]) delivered by DPI. The proportion of subjects with any post-treatment adverse event for ARF 15, ARF 25 microg, and FORM was 67.8%, 76.2% and 66.7%, respectively, and those with at least one COPD exacerbation was 32.2%, 30.6%, and 22.4%, respectively. Pulmonary function improved for all treatment groups and was maintained throughout the study. Mean change from baseline at 6-months for ARF 15, ARF 25 and FORM in peak FEV(1) was 0.30L, and 0.34L, and 0.26L, respectively, in 24-hour trough FEV(1) was, 0.10L, 0.14L, and 0.09L, and in inspiratory capacity was, 0.20L, 0.37L, and 0.23L. Dyspnea, (mean Transition Dypsnea Index (TDI) focal score) improved in all treatment arms (ARF 15: 1.4, ARF 25: 1.5, and FORM: 1.4) at 6 months, as did rescue short-acting beta(2)-agonists use (mean range: -1.1 to -1.3 actuations/day) and ipratropium bromide (mean range: -0.3 to -0.8 actuations/day). Health status, measured by St George's Respiratory Questionnaire, improved from baseline at 6-months in all treatment groups (mean change: -3.7 to -6.8). In this 6-month study, arformoterol and formoterol were well-tolerated, and their use was associated with improvement in pulmonary function and health status in subjects with COPD with no apparent development of tolerance.