Evaluation of Construct and Criterion Validity for the ‘Liverpool Osteoarthritis in Dogs’ (LOAD) Clinical Metrology Instrument and Comparison to Two Other Instruments

Objective

To test the ‘Liverpool Osteoarthritis in Dogs’ (LOAD) questionnaire for construct and criterion validity, and to similarly test the Helsinki Chronic Pain Index (HCPI) and the Canine Brief Pain Inventory (CBPI).

Design

Prospective Study.

Animals

222 dogs with osteoarthritis.

Procedure

Osteoarthritis was diagnosed in a cohort of dogs on the basis of clinical history and orthopedic examination. Force-platform analysis was performed and a “symmetry index” for peak vertical force (PVF) was calculated. Owners completed LOAD, CBPI and HCPI instruments. As a test of construct validity, inter-instrument correlations were calculated. As a test of criterion validity, the correlations between instrument scores and PVF symmetry scores were calculated. Additionally, internal consistency of all instruments was calculated and compared to those previously reported. Factor analysis is reported for the first time for LOAD, and is compared to that previously reported for CBPI and HCPI.

Results

Significant moderate correlations were found between all instruments, implying construct validity for all instruments. Significant weak correlations were found between LOAD scores and PVF symmetry index, and between CBPI scores and PVF symmetry index.

Conclusion and Clinical Relevance

LOAD is an owner-completed clinical metrology instrument that can be recommended for the measurement of canine osteoarthritis. It is convenient to use, validated and, as demonstrated here for the first time, has a correlation with force-platform data.     

Fish oil before cardiac surgery: neutrophil activation is unaffected but myocardial damage is moderated

Could pre-operative dietary intervention with fish oil reduce neutrophil activation and myocardial damage associated with cardiopulmonary bypass (CPB)? Patients were randomised to receive either 8 g/day fish oil (n=22) or placebo (n=18) for 6 weeks. Neutrophil activation, apoptosis and cardiac damage were measured. Demographics and operative variables were similar. Fish oil diet decreased plasma VLDL from 0.69+/-0.34 to 0.51+/-0.24 mmol/l and triglycerides from 1.68+/-0.70 to 1.39+/-0.54 mmol/l. HDL cholesterol increased from 0.94+/-0.27 to 1.03+/-0.26 mmol/l demonstrating significant treatment effects (P=0.007, 0.02 and 0.0003, respectively) as well as compliance with treatment. There were no significant differences in ex vivo N-formyl-methionyl-leucyl-phenylalanine-stimulated neutrophil superoxide anion generation or myeloperoxidase release at recruitment, pre-operatively and at end-CPB. Apoptosis at end-CPB was equally reduced in both groups from 23+/-9% to 13+/-4% in the fish oil group (P<0.001) and 35+/-14% to 15+/-3% in the placebo group (P=0.001). At end-CPB overall troponin I levels averaged 0.91+/-0.60 ng/ml which clearly exceeded diagnostic levels (0.15 ng/ml). At 24h troponin I fell significantly in the fish oil group to 46+/-23% of end-CPB levels (P=0.0002) whereas it peaked in the placebo group to 107+/-72% (P=0.098 vs. end-CPB); this difference was significant: P=0.013. At 48 h the placebo-treated patients had higher troponins but not significantly so (P=0.059). Area-under-the-curve analysis did not conclusively support this (P=0.068). We conclude that fish oil did not significantly decrease post-CPB neutrophil activation (as detected ex vivo) but may moderate post-operative myocardial damage.     

Stratification,Blinding and Placebo Effect in a Randomized,Double Blind Placebo-controlled Clinical Trial of Gold Bead Implantation in Dogs with Hip Dysplasia

The purpose of this study was to investigate the need for and choice of stratification factors, and the effects of blinding and placebo in a clinical experiment. Eighty dogs with canine hip dysplasia (CHD) were included in a randomized, placebo-controlled and double blind clinical trial with stratified parallel group design, in which body weight and degree of CHD were used as stratification factors. Thirty-eight dogs were allocated to gold bead implantation and 42 to placebo. After six months, 33 of the 42 placebo-treated dogs received gold bead implantation in an open study lasting a further 18 months. The main outcome variable in the study was change in pain signs of CHD as assessed by the owner. No significant difference in the main outcome variable, regardless of the treatment given, could be detected in the two chosen stratification factors. The only factor to influence the main outcome variable significantly was age. The blinding procedure used in the study, in which 60% of the owners correctly guessed the treatment given, was found sufficient. Of those who guessed the treatment erroneously, 88% believed the treatment given was gold bead implantation. The treatment efficacy after six months in the blinded treatment group was found to be significantly larger compared to the efficacy obtained in the open study. A significant placebo effect was therefore detected. Conclusion and Clinical Relevance: The age of the dogs influenced the outcome of the CHD treatment, and is recommended as a stratification factor. A significant placebo effect has to be expected and an optimal blinding procedure is necessary in similar clinical studies.     

Liver blood flow during haemorrhagic shock in the dog treated with phenoxybenzamine

The liver blood flow has been extensively studied in hemorrhagic shock, but considerable disagreement exists as to the nature of hemodynamic changes and their controlling mechanism. The present investigation was undertaken in order to determine the effects of hemorrhage and phenoxybenzamine (PBZ) on the participation of hepatic artery (HAF) and portal vein flow (PVF) in total liver blood flow (LBF) changes. The dynamics of LBF (H2 washout method), HAF and PVF (electromagnetic flowmeter) during 3-hours posthemorrhagic hypotension (90 min. = 50-60 mmHg; 90 min. = 25-30 mmHg) and one-hour postretransfusion period were investigated on 20 mongrel dogs under chloralose anesthesia. All animals were divided into 2 groups (control and PBZ-treated--5 mg/kg b.w. 30 minutes following first bleeding). Half an hour following bleeding there occurred a significant decrease of LBF (P less than 0.001) in dogs of both experimental groups. This degree of decrease was due to equal decrease in the PVF and HAF. The infusion of PBZ caused a slight tendency towards increase of LBF, while the subsequent decrease in blood flow values during second hypotensive period in the treated dogs was not so pronounced as in the untreated dogs. Although retransfusion led to an increase of LBF, HAF and PVF in both groups, the restauration was significantly better in PBZ-treated animals. The degree of metabolic acidosis was more pronounced in the untreated dogs than in PBZ-treated.     

Analgesic effect of nasal salmon calcitonin during the early post-fracture period of the distal radius fracture

Objectives:

To investigate the analgesic effect of nasal salmon calcitonin on the post-fracture period of distal radius fracture.

Methods:

In this prospective randomized double-blind study, forty-one postmenopausal women with a recent distal radius fracture treated conservatively were randomly assigned to receive either 200 IU of intranasal salmon calcitonin or placebo daily for 3 months following fracture. The assessment of the patient’s pain was recorded using the Visual Analogue Scale (VAS).

Results:

The average age of the calcitonin group was 67.11 (SD, ±8.68) years and 64.91 (SD, ±7.48) of the placebo group. In the calcitonin group, the mean VAS score improved from 4.05 to 0.53 while in the placebo group from 3.36 to 0.32. A higher decrease of VAS score during the first post-fracture period was observed in the calcitonin group.

Conclusions:

In the study, there is a statistically significant calcitonin mediated analgesic effect in the immediate post fracture period (at 10 days) when compared to placebo group. These results are in accordance with literature referring to the analgesic effect of calcitonin in the acute osteoporotic vertebral compression fracture. Thus calcitonin administration could be recommended to a short term course in acute osteoporotic conservatively treated distal radius fractures.     

Treatment of separation anxiety in dogs with clomipramine: results from a prospective, randomized, double-blind, placebo-controlled, parallel-group, multicenter clinical trial

The efficacy and tolerability of clomipramine in the treatment of separation anxiety in dogs was tested in a prospective, randomized, double-blind, placebo-controlled, parallel-group, international multicenter clinical trial. For a diagnosis of separation anxiety, dogs had to exhibit at least one of the following signs in the absence of their owner: destruction, defecation, urination and/or vocalization, as well as the behaviour suggestive of "hyper-attachment" to their owner. A total of 95 dogs were randomized to receive one of the three treatments for 2-3 months: "standard-dose" clomipramine (1 to <2 mg/kg, PO, q. 12 h); "low-dose" clomipramine (0.5 to <1 mg/kg, PO, q. 12 h); and placebo (PO, q. 12 h). All dogs received behavioural therapy. Dogs were examined at four time points (days 0, 28, 56 and 84) after the initiation of therapy. Improvement in each dog's behaviour at days 28, 56 and 84 was evaluated in comparison to its behaviour at day 0.The results showed that, compared to placebo, dogs receiving standard-dose clomipramine were rated improved at least three times faster for the signs destruction, defecation and urination. At most time points, more dogs in the standard-dose clomipramine group were rated improved for the signs destruction, defecation and urination, and in an owner's global assessment of the dog's overall behaviour (p<0.05 at certain time points). However, there were no statistically significant differences at any time point between the standard dose and the placebo groups in the sign vocalization. The low-dose clomipramine group produced no statistically significant effect when compared with placebo. Mild and transient vomiting was noted as a side effect of clomipramine in a small number of dogs.It is concluded that addition of standard-dose (1 to <2 mg/kg, PO, q. 12 h) clomipramine to conventional behavioural therapy for 2-3 months ameliorated the signs of separation anxiety in dogs.     

Long-term intake of edible oils benefits blood pressure and myocardial structure in spontaneously hypertensive rat (SHR) and streptozotocin diabetic SHR

The beneficial effects of edible oils long-term supplementation in blood pressure (BP) and cardiac structure were investigated in spontaneously hypertensive rat (SHR) and streptozotocin diabetic (Db) SHR (45 mg/rat i.p.). Twenty-five 12-week old male SHR were divided into four SHR-Db groups and one SHR group, SHR-Db groups each receiving, respectively, olive oil, palm oil and fish oil, and another SHR-Db group with placebo by gavage on a daily basis for 6 weeks. Myocardial structures were analyzed through light microscopy and stereology. In SHR-Db, the BP and the myocardium were significantly altered by oil supplementation. The BP, the interstitial fibrosis and cardiomyocyte size showed a significant decrease in treated SHR-Db than in SHR or untreated SHR-Db. The myocardial microvasculature and number of cardiomyocytes were higher in all treated groups, especially in fish oil group. Long-term edible oil supplementation showed beneficial effects decreasing BP levels and offsetting adverse myocardial remodeling in diabetic SHR.     

The effects of stress induced by cortisol administration on the repeatability of swimming performance tests in the European sea bass (Dicentrarchus labrax L.)

The impact of stress induced by cortisol administration on the swimming performance of the European sea bass was tested measuring the fish recovery capability using a respirometer. The recovery test consisted of two exhaustive swimming exercises (U _crit) separated by a recovery period. Thirty-eight fish were subjected to this trial preceded or not (control group) by a cortisol (cortisol group) or saline (placebo) injection. For validation, the classical stress parameters (cortisol, glucose, lysozyme, Hct, Hb and RBCC) were monitored. During the recovery tests, only the cortisol group showed a significant reduction in the recovery capability that was interpreted as a sign of possible physiological impairment. Hct, Hb and RBCC did not show significant inter and intra-group differences, while cortisol and glucose increased as a response to fatigue in all the groups at the end of the trials. No immune (lysozyme) response was observed in control and placebo groups, while a reduction was evidenced in the cortisol group.     

Determinants of DHA levels in early infancy: differential effects of breast milk and direct fish oil supplementation

IntroductionAlthough omega (n)-3 long-chain polyunsaturated fatty acids (LCPUFA), particularly docosahexaenoic acid (DHA), intakes are important during infancy, the optimal method of increasing infant status remains unclear. We hypothesized that high-dose infant fish oil supplementation would have greater relative effects upon n-3 LCPUFA status at six months of age than breast milk fatty acids.Patients and methodsInfants (n=420) were supplemented daily from birth to six months with fish oil or placebo. In a subset of infants, LCPUFA levels were measured in cord blood, breast milk and in infant blood at 6 months.ResultsDHA levels increased in the fish oil group relative to placebo (p<05). Breast milk DHA was the strongest predictor of infant erythrocyte DHA levels (p=<001). This remained significant after adjustment for cord blood DHA, supplementation group and adherence.ConclusionIn this cohort, breast milk DHA was a greater determinant of infant erythrocyte n?3 LCPUFA status, than direct supplementation with fish oil.     

ω-3 oil intake during weight loss in obese women results in remodelling of plasma triglyceride and fatty acids

Previous studies have shown that a combination of weight loss and fish oil supplementation reduce cardiovascular disease and diabetes risks by increasing adiponectin and reducing triacylglyceride concentrations, while weight loss alone significantly improves insulin sensitivity and reduces inflammation. Here, a metabolomic approach, using a combination of ¹H-Nuclear Magnetic Resonance spectroscopy, and gas and liquid chromatography and mass spectrometry, was employed to elucidate the metabolic changes in blood plasma following weight loss and fish oil supplementation. The intervention study was conducted over 24 weeks, with 93 female subjects randomised to one of three groups. Two groups followed a 12-week weight loss program, followed by a 12-week weight maintenance period and were randomised to fish or placebo oil capsules; a control group did not follow the weight loss program and were given placebo oil capsules. Lipid profiles changed dramatically upon fish oil intake and subtly across the two weight loss groups. While the fish oil supplementation increased the proportion of various phospholipid species, previously reported reductions in total triacylglycerides (TAGs) upon fish oil intake were shown to be driven by a reduction in a specific subset of the measured TAGs. This remodelling of triglycerides may represent further beneficial effects of fish oil supplementation.     

Mapping abundance distribution of small pelagic species applying hydroacoustics and Co-Kriging techniques

Hydroacoustic technology provides ground tools for the estimation of abundance and spatial distribution of pelagic species. The final products of such surveys, the interpolated choropleth maps, are based on a Geostatistical analysis of the acoustic measurements to minimise, as much as possible, the interpolation error, and to quantify uncertainty. The current study is based on fisheries acoustic measurements and satellite images covering the sea area of Thermaikos Gulf over the years 1996, 1997 and 1998. Spatial interpolations describing the abundance and distribution of small pelagic species in the research area, as well as sea surface temperature (SST), Chlorophyll-a content (SSC) and average depth, were produced, based on Ordinary and Universal Kriging and Co-Kriging Geostatistical methods. The results of the Geostatistical analysis showed that the Co-Kriging spatial interpolation method produced the best results regarding fish abundance when SST and average depth variables were included in the model. The latter indicates that there is an existing spatial cross-correlation between fish abundance and the environmental variables. Consequently, the potential reduction of the overall error in the estimation process, as presented in this study, is very significant, particularly with regard to error reduction in stock assessment and management. Guest editor: V. D. Valavanis Essential Fish Habitat Mapping in the Mediterranean     

Validation of Orthopedic Postoperative Pain Assessment Methods for Dogs: A Prospective,Blinded, Randomized,Placebo-Controlled Study

In the context of translational research, there is growing interest in studying surgical orthopedic pain management approaches that are common to humans and dogs. The validity of postoperative pain assessment methods is uncertain with regards to responsiveness and the potential interference of analgesia. The hypothesis was that video analysis (as a reference), electrodermal activity, and two subjective pain scales (VAS and 4A-VET) would detect different levels of pain intensity in dogs after a standardized trochleoplasty procedure. In this prospective, blinded, randomized study, postoperative pain was assessed in 25 healthy dogs during a 48-hour time frame (T). Pain was managed with placebo (Group 1, n = 10), preemptive and multimodal analgesia (Group 2, n = 5), or preemptive analgesia consisting in oral tramadol (Group 3, n = 10). Changes over time among groups were analyzed using generalized estimating equations. Multivariate regression tested the significance of relationships between pain scales and video analysis. Video analysis identified that one orthopedic behavior, namely ‘Walking with full weight bearing’ of the operated leg, decreased more in Group 1 at T24 (indicative of pain), whereas three behaviors indicative of sedation decreased in Group 2 at T24 (all p<0.004). Electrodermal activity was higher in Group 1 than in Groups 2 and 3 until T1 (p<0.0003). The VAS was not responsive. 4A-VET showed divergent results as its orthopedic component (4A-VETleg) detected lower pain in Group 2 until T12 (p<0.0009), but its interactive component (4A-VETbeh) was increased in Group 2 from T12 to T48 (p<0.001). Concurrent validity established that 4A-VETleg scores the painful orthopedic condition accurately and that pain assessment through 4A-VETbeh and VAS was severely biased by the sedative side-effect of the analgesics. Finally, the video analysis offered a concise template for assessment in dogs with acute orthopedic pain. However, subjective pain quantification methods and electrodermal activity need further investigation.     

A randomized,double-blind,prospective, placebo-controlled study of the efficacy of a diet supplemented with curcuminoids extract,hydrolyzed collagen and green tea extract in owner’s dogs with osteoarthritis

Background

We have previously demonstrated that a mixture of Curcuminoids extract, hydrolyzed COllagen and green Tea extract (CCOT) inhibited inflammatory and catabolic mediator’s synthesis by bovine and human chondrocytes. A randomly allocated, double-blind, prospective, placebo-controlled study was performed to evaluate the efficacy of a diet containing this CCOT mixture on dogs with naturally occurring osteoarthritis (OA). Therefore, 42 owner’s dogs with OA were randomly assigned to receive for 3 months an experimental diet (control) or the same diet supplemented with CCOT.

Results

Ground reaction forces did not show statistical differences between groups. After 3 months of feeding, there was a significant reduction of pain at manipulation in the CCOT group, but not in the control group. The evolution for pain at manipulation depended on the diet. The three other parameters evaluated by veterinary subjective assessment (lameness, pain at palpation and joint mobility) did not show statistical differences. Concerning owner subjective assessment, pain severity score worsened in the control group but remained stable in CCOT group. The evolution for pain severity depended on the diet. No statistical difference was found for pain interference, except for the ability to rise to standing from lying down, which was significantly improved in the CCOT compared to the control group. Serum OA biomarkers did not show statistical differences.

Conclusions

Objective variables measured, such as ground reaction forces and OA biomarkers, did not show statistical differences. However, indicators of pain appeared reduced in dogs receiving CCOT mixture for 3 months. The difference of evolution between groups suggests that a greater number of dogs may be necessary to reach a stronger effect on other parameters.

     

Efficacy of a comfrey root (Symphyti offic. radix) extract ointment in the treatment of patients with painful osteoarthritis of the knee: results of a double-blind, randomised, bicenter, placebo-controlled trial.

This randomised, double-blind, bicenter, placebo-controlled clinical trial investigated the effect of a daily application of 6g Kytta-Salbe f (3 x 2 g) over a 3 week period with patients suffering from painful osteoarthritis of the knee. The two hundred and twenty patients examined consisted of 153 women and 67 men of an average age of 57.9 years. On average, the complaints relating to osteoarthritis of the knee had persisted for 6.5 years. Two hundred and twenty patients were included in the Full Analysis Set (FAS) and safety collective, 186 (84.5%) in the Valid Case Analysis Set (VCAS) collective. In the course of the trial, the visual analog scale (VAS) total score (primary target value) in the verum group dropped by 51.6 mm (54.7%) and in the placebo group by 10.1 mm (10.7%). The average difference between the groups of 41.5 mm (95% confidence interval=34.8 to 48.2 mm) or 44.0% is significant (p<0.001). The significance is confirmed through the evaluation of the diary, the VCAS evaluation and the separate assessment of the two centres. This also applies to the separate assessment of the VAS total score following pain at rest and on movement. The WOMAC (Western Ontario and McMaster Universities) total score (secondary target value) also improved similar to the VAS total score. At the end of the trial, a reduction by 60.4 mm (58.0%) was recorded for the verum group and a reduction of 14.7 mm (14.1%) for the placebo group. The average group difference of 45.7 mm (95% confidence interval=37.1 to 54.3 mm) or 43.9% is significant (p<0.001). The difference between the treatment groups increased systematically and significantly, in parallel with the duration of the treatment. Thus, the superiority of the treatment with Kytta-Salbe f over that with the placebo is proven, even by means of the multi-factorial multivariate analysis for repetitive measurements. In respect of the explorative secondary target values SF-36 (quality of life), angle measurement (mobility of the knee), CGI (clinical global impression) and global assessment of efficacy by the physician and the patient, a significant superiority (p<0.001 each) of the verum group over the placebo group was also proven. The results suggest that the comfrey root extract ointment is well suited for the treatment of osteoarthritis of the knee. Pain is reduced, mobility of the knee improved and quality of life increased.     

Fish oil and neurovascular control in humans

The antihypertensive influence of fish oil is controversial, and the mechanisms remain unclear. Because the inverse relation between fish oil and hypertension appears to be partially dependent on the degree of hypertension, we tested the hypothesis that fish oil would elicit more dramatic reductions in mean arterial pressure (MAP) and muscle sympathetic nerve activity (MSNA) in prehypertensive (PHT) compared with normotensive (NT) subjects. Resting MAP, MSNA, and heart rate (HR) were examined before and after 8 wk of fish oil (9 g/day; 1.6 g eicosapentaenoic acid and 1.1 g docosahexaenoic acid) or placebo (olive oil; 9 g/day) in 38 NT (19 fish oil; 19 placebo) and 29 PHT (15 fish oil; 14 placebo) volunteers. Fish oil did not alter resting MAP, MSNA, or HR in either NT (80 ± 1 to 80 ± 1 mmHg; 11 ± 2 to 10 ± 1 bursts/min; 71 ± 2 to 71 ± 2 beats/min) or PHT (88 ± 2 to 87 ± 1 mmHg; 11 ± 2 to 10 ± 2 bursts/min; 73 ± 2 to 73 ± 2 beats/min) subjects. When NT and PHT groups were consolidated, analysis of covariance confirmed that pretreatment resting MAP was not associated with changes in MSNA after fish oil. In contrast, pretreatment resting HR was correlated with changes in MSNA (r = 0.47; P = 0.007) and MAP (r = 0.42; P < 0.007) after fish oil but not placebo. In conclusion, fish oil did not alter sympathetic neural control in NT or PHT subjects. However, our findings suggest that fish oil is associated with modest sympathoinhibition in individuals with higher resting heart rates, a finding that is consistent with a recent meta-analysis examining the relations among fish oil, HR, and the risk of cardiovascular disease.     

亚麻籽油和豆油替代鱼油对大黄鱼肝脏和肌肉脂肪酸组成及Δ6Fad基因表达的影响

为了研究亚麻籽油(LO)和豆油(SO)完全替代鱼油(FO)对大黄鱼(Larimichthys crocea)肝脏和肌肉脂肪酸组成及Δ6Fad (Δ6 Fatty acid desaturase)基因表达的影响。实验用豆油和亚麻籽油替代鱼油制备了3种等氮等脂的精制饲料, 在海水浮动网箱中进行了为期10周的养殖实验。实验结果表明: (1)鱼油组的增重率、饲料效率和特定生长率均显著高于亚麻籽油组和豆油组(P<0.05), 但对成活率, 肝体指数和脏体指数没有显著影响(P>0.05); (2)亚麻籽油和豆油完全替代鱼油显著改变了鱼体肝脏和肌肉的脂肪酸组成, 降低了肝脏和肌肉LC-PUFA (Long chain-polyunsaturated fatty acid)的相对含量(P<0.05), 在亚麻籽油组(LO)和豆油组(SO)中没有显著差异(P>0.05), 在各处理组中, 肌肉的n-3LC-PUFA的相对含量显著高于肝脏(P<0.05); (3)亚麻籽油和豆油显著上调了肌肉和肝脏中Δ6Fad基因的表达量(P<0.05), 其表达量在肝脏中分别升高了7.6和6.5倍, 在肌肉中分别上升了2.2和2.8倍。结果表明, 在实验条件下亚麻籽油和豆油完全替代鱼油对大黄鱼生长具有不利影响, 亚麻籽油和豆油替代鱼油降低了肝脏和肌肉中LC-PUFA的含量, 提高了Δ6Fad基因的表达量。     

A Randomised Placebo-Controlled Trial to Differentiate the Acute Cognitive and Mood Effects of Chlorogenic Acid from Decaffeinated Coffee

In the current study, sixty healthy older adults aged 50 years or older, and who were light to moderate coffee drinkers, were administered 6g of a decaffeinated green coffee blend (NESCAFÉ Green Blend coffee; GB) or 540mg pure chlorogenic acids (CGA) or placebo in a double-blind acute cross-over design, with cognitive and mood assessments pre-dose, 40-mins and 120-mins post-dose. The primary outcome measure was accuracy in Rapid Visual Information Processing (RVIP). Secondary cognitive outcome measures included RVIP reaction time as well as Inspection time (IT), Jensen Box decision/reaction times, serial subtraction and N-Back working memory. Secondary mood measures included Bond-Lader and caffeine Research visual analogue scales (VAS). No significant treatment effects were found for the primary outcome measure, although significant effects were found amongst secondary measures. Overall, CGA in isolation was not found to significantly improve cognitive function relative to placebo whereas the GB was found to improve sustained attention as measured by the N-Back task in comparison to placebo overall (t=2.45,p=.05), as well as decision time on a 2-choice reaction time task (Jensen box) in comparison to placebo at 40 minutes post-dose (t=2.45,p=.05). Similarly, GB was found to improve alertness on both the Bond-Lader at 120 minutes relative to CGA (t=2.86, p=0.02) and the caffeine Research VAS relative to CGA (t=3.09, p=0.009) and placebo (t=2.75,p=0.02) at 120 minutes post-dose. Both the GB and CGA were also found to significantly improve symptoms of headache at 120 minutes relative to placebo (t=2.51,p=0.03 and t=2.43,p=.04 respectively), whilst there was a trend towards a reduction in jitteriness with GB and CGA in comparison to placebo at 40 minutes post-dose (t=2.24,p=0.06 and t=2.20,p=0.06 respectively). These findings suggest that the improvements in mood observed with GB, but not the improvements in cognitive function, are likely to some extent to be attributable to CGAs.Trial Registration: Australia New Zealand Clinical Trials Registry ACTRN12611000067976 www.anzctr.org.au     

Risk factors and milk yield losses associated with lameness in Holstein-Friesian dairy cattle

Weekly locomotion scores on a scale of 1 to 5 were used to investigate the relationship between cattle lameness, management systems and the impact of lameness on milk production. The data were 14026 locomotion scores from 248 Holstein-Friesian cows. Cows were managed in two groups, XE (high-concentrate feed and housed indoors all year) and XM (low-concentrate feed and outdoors in summer). Analysis was performed using residual maximum likelihood. Results indicated that the most significant variables affecting locomotion were time of year when the animal was locomotion scored and management group. Cows scored during February and August had increased locomotion problems. Cows in the more intensively managed group had significantly poorer locomotion compared with those in the more extensive group. Older animals were more susceptible to lameness than heifers. Body weight, body condition score and days in milk (DIM) also accounted for significant variation in locomotion score. Poor locomotion was associated with a significant reduction in the milk yield of later lactation cows. There was a significant difference in the shape of the lactation curve depending on whether or not the cow was lame during lactation. Average persistency was greater for the group of cows never lame throughout lactation compared with those lame before 60 DIM.