Behavioural responses of lambs to plastic clips as an alternative procedure to mulesing.

OBJECTIVE: Compare the effects on the behaviour of lambs of applying occlusive plastic clips, as an alternative procedure to surgical mulesing, with tail docking, surgical mulesing and a control treatment. PROCEDURE: We allocated 48 6-7-week-old Merino lambs to four treatment groups: plastic clips (Clip); surgical mulesing (Mules); tail docking with a rubber ring (Tail ring); no treatment (Control). For each posture and behaviour observed on each of the 4 days post-treatment, a Dunnett's multiple comparison test was used to simultaneously compare the Clip treatment with each of the comparator treatments (Control, Tail ring and Mules treatments). RESULTS: Most of the significant differences (P < 0.05) detected between the comparator treatments occurred on day 1. For four of these measurements, the Clip treatment differed (P < 0.01) from the Mules treatment, but from not the Control and Tail ring treatments: the Clip lambs spent less time standing immobile not interacting with ground, hay or feeder, less time standing immobile head down not interacting with ground, hay or feeder, more time walking and more time interacting with ground, hay or feeder. CONCLUSION: These behavioural results, together with previous behavioural and physiological research, indicate that the effect on lamb welfare of applying occlusive clips is less than that of surgical mulesing.

The effect of breed, time spent with dam and late pregnancy induction of parturition on behavioural development in dairy calves.

Three experiments examined the impact of breed, time spent with dam (TWD), gender, and late pregnancy induction of parturition and caesarean on the behavioural and heart rate responses of dairy calves at 2 and 6 weeks of age to Open field, Novel object and Startle tests and a Learning task. In Experiment 1 with male Jersey, Friesian and Friesian x Angus calves, there were some significant breed effects on responses to the Open field and the Novel object tests; Jersey calves appeared more curious and less fearful than Friesian x Angus calves. In Experiment 2, in which male and female Friesian calves were removed from their dams either between 0 and 12h or 12 and 24h after birth, there were no significant effects of gender or TWD. In Experiment 3, which studied the effect of induction of parturition using a long-acting glucocorticoid combined with short-acting progesterone 10 days prior to due calving date, there were no significant effects of late pregnancy induction of parturition. Across all three experiments, age at testing was the main factor influencing the responses of the calves. However, a number of interactions suggest that gender, time spent with dam and late pregnancy induction of parturition modified some of the responses to the tests as the calves developed.

Mutation in bovine beta-carotene oxygenase 2 affects milk color.

beta-Carotene biochemistry is a fundamental process in mammalian biology. Aberrations either through malnutrition or potentially through genetic variation may lead to vitamin A deficiency, which is a substantial public health burden. In addition, understanding the genetic regulation of this process may enable bovine improvement. While many bovine QTL have been reported, few of the causative genes and mutations have been identified. We discovered a QTL for milk beta-carotene and subsequently identified a premature stop codon in bovine beta-carotene oxygenase 2 (BCO2), which also affects serum beta-carotene content. The BCO2 enzyme is thereby identified as a key regulator of beta-carotene metabolism.

The effects of a perch, dust bath, and nest box, either alone or in combination as used in furnished cages, on the welfare of laying hens.

This experiment examined the welfare-related effects of individual furniture items alone or in combination in a factorial experiment using Hy-Line Brown hens housed in 8-bird furnished cages. Welfare was assessed during two 8-wk sampling periods commencing at 29 and 59 wk of age. Measurement of stress, immunology, feather, foot and claw condition, and behavior were taken, and bone strength was measured at the end of the experiment. With the exception of the positive effects of a perch on bone strength, any effects of furniture items were relatively small, even though the furniture was extensively used. Although there were changes in behavior and small changes in feather, foot, and claw condition, it is unclear whether these changes have any meaningful implications for welfare. In this experiment there were 2 additional external control treatments for a small study that examined the effects of increasing space per bird (8 birds in single- and double-width cages) and the effects of group size (8 and 16 birds in double-width cages); using similar methodologies, these treatments showed differences in egg corticosterone concentrations and evidence of immunosuppression. Together, these data suggest that although furniture when present was well-used, any effects of furniture on hen welfare measured by physical and physiological traits, other than the benefit of a perch on bone strength, were smaller than effects of group size and space allowance.

Behavioural responses of poultry during kosher slaughter and their implications for the birds' welfare.

Measurements were made during Shechita (kosher) slaughter of 692 meat chickens, including the behaviour of the birds during the procedure and the times from their removal from the crate, to neck cutting, bleed-out and shackling. Four of 100 birds showed a mild physical response to neck cutting but the others showed no response. Approximately 60 per cent of the birds showed a physical response to touching the eye or eyelid at up to 5 seconds after neck cutting, but by 15 seconds none showed this response. The birds became unable to retain their posture and suffered involuntary muscular contractions at 12 to 15 seconds after neck cutting and had lost approximately 40 per cent of their total blood volume by 30 seconds after neck cutting.

Sources of sampling variation in saliva cortisol in dogs.

The main advantage of collecting saliva cortisol as opposed to plasma cortisol is that it is non-invasive and therefore it is now widely used in stress measurement studies on farm animals and dogs. Although a plasma cortisol response to handling associated with blood collection generally occurs at 3 min from the commencement of handling, there is no information in the literature on the time course of the response of salivary cortisol concentration to handling. The aims of these experiments were to (1). determine if there is a response to up to 4 min handling that affects cortisol concentration in saliva and (2). determine the main causes of variation in saliva cortisol in dogs over time. In experiment 1, saliva was collected from six Kelpies at 0 min then 2, 3 or 4 min after the commencement of restraint. There was no handling effect found in up to 4 min sampling time. In experiment 2, saliva was collected from six Labrador Retrievers five times in 2 h (14:00-16:00), three days a week for four weeks. Some of the sources of variation in saliva cortisol over time included between dog variation that varied over a period of days and variation between occasions that affected the group of dogs as a whole.

Electrogastrography: a document prepared by the gastric section of the American Motility Society Clinical GI Motility Testing Task Force.

The objective of this document is to present the consensus opinion of the American Motility Society Clinical GI Motility Testing Task Force on the performance and clinical utility of electrogastrography (EGG). EGG is a non-invasive means of recording human gastric myoelectrical activity or slow waves from cutaneous leads placed over the stomach. In healthy volunteers, EGG tracings exhibit sinusoidal waveforms with a predominant frequency of 3 cycles per minute (cpm). Clinical studies have shown good correlation of these cutaneous recordings with those acquired from serosally implanted electrodes. The amplitude of the EGG waveform increases with ingestion of caloric or non-caloric meals. Some patients with nausea, vomiting, or other dyspeptic symptoms exhibit EGG rhythm disturbances or blunting of meal-evoked EGG signal amplitude increases. These abnormalities correlate to some degree with delayed gastric emptying of solids. In selected patients, EGG may be complementary to gastric emptying testing. To date, no therapies have convincingly demonstrated in controlled studies that correcting abnormalities detected by EGG improves upper gastrointestinal symptoms. Proposed clinical indications for performance of EGG in patients with unexplained nausea, vomiting and dyspeptic symptoms must be validated by prospective controlled investigations.

Science and its application in assessing the welfare of laying hens in the egg industry.

OBJECTIVE: To provide a rational framework for the scientific assessment of welfare and to use this framework to assess the welfare implications of issues relevant to the Australian egg industry. PROCEDURE: A well-accepted approach to the assessment of animal welfare, based on assessing how well the animal is adapting, is described. This approach is used to consider the welfare implications of issues such as space, perches, nest boxes, dust baths, abrasive strips and non-cage housing systems. CONCLUSIONS: The role of science in the welfare debate is to provide biological facts and thus it is important to separate welfare and ethics. The welfare of an animal in response to a housing system or husbandry procedure can be assessed by evaluating how much has to be done by the animal in order to cope and the extent to which the coping attempts are succeeding. Using this approach there is evidence for improved welfare from increasing space in cages, based on reduced aggression, corticosterone concentrations and mortalities and increased production, and for incorporating perches, based on the reduction in injuries at depopulation. Similar evidence for the inclusion of dust baths and nest boxes is lacking. The data on abrasive strips are equivocal with recommendations from overseas for their inclusion, whereas some local data have shown an increase in mortality can occur. Similarly, the data on non-cage systems are equivocal. The data on bone strength suggest improved fitness in non-cage systems, the data on stress suggest fitness may be better, similar or worse in non-cage systems, and the limited data on immunology suggest fitness may be worse in non-cage systems than in conventional cages.

The effects of cognitive behavioral intervention on the attitude and behavior of stockpersons and the behavior and productivity of commercial dairy cows.

Two experiments, one involving 29 commercial farms and the other involving 94 commercial farms, were conducted to examine the effects of a training program targeting a number of attitudinal and behavioral variables in stockpeople. These stockperson variables had been previously shown to be related to fear of humans and productivity of commercial cows. In both experiments, two treatments were imposed: an Intervention treatment, consisting of a cognitive-behavioral intervention procedure designed to improve the attitude and behavior of stockpeople toward cows, and a Control treatment, in which no intervention was attempted. In Exp. 1, an analysis of covariance, using previous lactation variables as the covariate, revealed effects of the Intervention treatment on the attitude and behavior of the stockpeople and the behavior of cows. Stockpeople at Intervention farms showed more (P < 0.01) positive beliefs about handling cows and used a lower (P < 0.05) number and percentage of negative tactile interactions in handling cows than stockpeople at the Control farms. Cows at the Intervention farms showed a shorter (P < 0.05) flight distance to humans, indicating a lower level of fear of humans by these cows. However, 36% of the Intervention farms failed to show a reduction in average flight distance over the two lactations. Although there was no significant treatment effect on milk yield, the Intervention farms in which fear levels declined following the intervention had a higher (P < 0.05) milk yield than the other farms. In Exp. 2, a significant (P < 0.05) increase was found in the milk yield of cows following the Intervention treatment. Similar treatment effects were observed on both milk protein and milk fat. These results indicate that cognitive-behavioral interventions that successfully target the key attitudes and behavior of stockpeople that regulate the cow's fear of humans offer the industry good opportunities to improve the productivity of cows.

Optimizing acid-suppression therapy.

Acid-related disorders are caused by an imbalance between acid secretion by the gastric parietal cells and the defensive mechanisms of the gastrointestinal tract to protect against the effects of acid. Therapy for acid-related disorders focuses on the control of acidity. Data collected throughout the last decade have demonstrated that PPIs are the most effective therapy for acid-related disorders: PPIs have proven superior to H2RAs and antacids in numerous studies. Five PPIs are currently available in the United States. While all PPIs exert their effect through the same basic mechanism of action, they do not have the same pharmacologic and clinical properties. All PPIs are effective in healing and maintenance of gastric and duodenal ulcers and GERD. The PPIs differ, however, in their ability to control symptoms rapidly and consistently. Due to its more rapid rate of activation, rabeprazole results in a faster onset of action and faster symptom control than other PPIs. Studies comparing rabeprazole to omeprazole found statistically significant differences in the rapidity of symptom relief in patients with gastric ulcer, duodenal ulcer, and GERD. Rapid symptom relief is important to the majority of patients, as their symptoms have an impact on their quality of life. Rapid symptom relief is also important in an environment where patients self-medicate on demand, depending on daily symptoms. Rabeprazole has also been shown to have a more consistent suppression of acid, including at night. Optimizing therapy with PPIs necessitates consideration not only of healing rates of the different available treatments but also of the rapidity and consistency of acid suppression that translate clinically into symptom relief.

Can endoscopic ultrasound or magnetic resonance cholangiopancreatography replace ERCP in patients with suspected biliary disease? A prospective trial and cost analysis.

OBJECTIVES: ERCP is the gold standard for pancreaticobiliary evaluation but is associated with complications. Less invasive diagnostic alternatives with similar capabilities may be cost-effective, particularly in situations involving low prevalence of disease. The aim of this study was to compare the performance of endoscopic ultrasound (EUS) with magnetic resonance cholangiopancreatography (MRCP) and ERCP in the same patients with suspected extrahepatic biliary disease. The economic outcomes of EUS-, MRCP-, and ERCP-based diagnostic strategies were evaluated. METHODS: Prospective cohort study of patients referred for ERCP with suspected biliary disease. MRCP and EUS were performed within 24 h before ERCP. The investigators were blinded to the results of the alternative imaging studies. A cost-utility analysis was performed for initial ERCP, MRCP, and EUS strategies for these patients. RESULTS: A total of 30 patients were studied. ERCP cholangiogram failed in one patient, and another patient did not complete MRCP because of claustrophobia. The final diagnoses (N = 28) were CBD stone (mean = 4 mm; range = 3-6 mm) in five patients; biliary stricture in three patients, and normal biliary tree in 20. Two patients had pancreatitis after therapeutic ERCP, one after precut sphincterotomy followed by a normal cholangiogram. EUS was more sensitive than MRCP in the detection of choledocolithiasis (80% vs 40%), with similar specificity. MRCP had a poor specificity and positive predictive value for the diagnosis of biliary stricture (76%/25%) compared to EUS (100%/100%), with similar sensitivity. The overall accuracy of MRCP for any abnormality was 61% (95% CI = 0.41-0.78) compared to 89% (CI = 0.72-0.98) for EUS. Among those patients with a normal biliary tree, the proportion correctly identified with each test was 95% for EUS and 65% for MRCP (p < 0.02). The cost for each strategy per patient evaluated was $1346 for ERCP, $1111 for EUS, and $1145 for MRCP. CONCLUSIONS: In this patient population with a low disease prevalence, EUS was superior to MRCP for choledocholithiasis. EUS was most useful for confirming a normal biliary tree and should be considered a low-risk alternative to ERCP. Although MRCP had the lowest procedural reimbursement, the initial EUS strategy had the greatest cost-utility by avoiding unnecessary ERCP examinations.

Novel method to assess gastric emptying in humans: the Pellet Gastric Emptying Test.

To further validate the Pellet Gastric Emptying Test (PGET) as a marker of gastric emptying, a randomized, four-way crossover study was conducted with 12 healthy subjects. The study consisted of oral co-administration of enteric coated caffeine (CAFF) and acetaminophen (APAP) pellets in four treatment phases: Same Size (100 kcal), Fasted, Small Liquid Meal (100 kcal), and Standard Meal (847 kcal). The time of first appearance of measurable drug marker in plasma, t(initial), was taken as the emptying time for the markers. Co-administration of same size enteric coated pellets of CAFF and APAP (0.7 mm in diameter) revealed no statistically significant differences in t(initial) values indicating that emptying was dependent only on size and not on chemical make-up of the pellets. Co-administration of different size pellets indicated that the smaller 0.7-mm diameter (CAFF) pellets were emptied and absorbed significantly earlier than the larger 3.6-mm diameter (APAP) pellets with both the Small Liquid Meal (by 35 min) and the Standard Meal (by 33 min) (P<0.05). The differences in emptying of the pellets were not significant in the Fasted Phase. The results suggest that the pellet gastric emptying test could prove useful in monitoring changes in transit times in the fasted and fed states and their impact on drug absorption.

Unsedated small-caliber esophagogastroduodenoscopy (EGD): less expensive and less time-consuming than conventional EGD.

BACKGROUND: A significant portion of the costs and complications of esophagogastroduodenoscopy (EGD) are related to the use of sedation. The feasibility and tolerability of small-caliber EGD (scEGD) without sedation has been evaluated; however, there is limited data concerning times and costs associated with this procedure as compared with conventional EGD (cEGD) with sedation. STUDY: Sixteen patients underwent scEGD with the Pentax EG-1840 (outside diameter, 6 mm) without sedation. A control group of 16 patients was matched for age, sex, day, and indication of procedure. The time of procedure, time in procedure room, time in recovery room, and procedure costs were determined in both the study and control groups. After the procedure, scEGD patients completed surveys consisting of visual-analogue scales to assess tolerance and preference regarding sedation for future procedures. RESULTS: Procedure time, procedure room time, and recovery room time was 5.2, 16.3, and 9 minutes for scEGD and 13.5, 34.9, and 41.3 minutes for cEGD, respectively (p < 0.001 for all comparisons). The mean cost of scEGD, excluding physician fees, was $462.00, which was significantly lower than the $587.00 for cEGD (p < 0.001). Survey results revealed good tolerance for the unsedated procedure. CONCLUSIONS: Unsedated scEGD was well tolerated and resulted in a shorter time of procedure, less time spent in procedure room, reduced recovery room time, and lower costs as compared with cEGD with sedation.

Management of the patient with gastroparesis.

Gastroparesis may be related to a variety of underlying disorders, but management options are fairly universal. Dietary measures and pharmacologic agents, primarily in the form of prokinetic medications, form the foundation of standard management. Some patients will have refractory symptoms and alternative dosing schemes or drug combinations may be used. An occasional patient will still require venting gastrostomy and/or jejunal feeding. This review addresses the standard dietary and pharmacologic approaches to gastroparesis, as well as issues pertaining to gastrostomy/jejunostomy tubes and to surgical options for refractory cases. Finally, experimental agents and techniques, such as gastric pacing, will be discussed.

Relationships between human-animal interactions and productivity of commercial dairy cows.

This study examined the relationships between a number of stockperson and cow variables at 66 commercial dairy farms. Variables such as the attitudes and behavior of stockpeople toward their cows and the behavioral response to humans and productivity of cows were studied over one lactation. There were consistent and significant correlations between some of these stockperson and cow variables. For example, a positive attitude by stockpeople toward the behavior of dairy cows was negatively correlated with the number of forceful, negative, tactile interactions used by stockpeople in handling cows (r = -0.27, df = 127, P < 0.01). Furthermore, based on farm averages, the number of forceful, negative, tactile interactions used by stockpeople was negatively correlated with the percentage of cows approaching within 1 m of an experimenter in a standard test (r = -0.27, df= 64, P< 0.05). Although not confirming a fear-productivity relationship, a moderate but nonsignificant correlation was found between flight distance of cows to an experimenter in a standard test and milk yield (r = -0.27, df = 33, P > 0.05). Support for the existence of a negative fear-productivity relationship was the finding that the use of negative interactions by stockpeople was significantly and negatively correlated with milk yield, protein, and fat at the farm (r = -0.36, -0.35 and -0.33, respectively, df = 64, P < 0.01) and was significantly and positively correlated with milk cortisol concentrations at the farm (r = 0.34, df= 64, P < 0.01). Furthermore, the percentage of cows approaching within 3 m of an experimenter in a standard test was positively correlated with conception rate to the first insemination (r = 0.38, df = 46, P < 0.01). The significant correlations found in the present study between stockperson attitudes and behavior and cow behavior and productivity, although not evidence of causal relationships, indicate the possibility of targeting these human characteristics to reduce fear responses of dairy cows to humans and improve the cows' productivity.

Routine droperidol pre-medication improves sedation for ERCP.

BACKGROUND: Pre-medication with droperidol has been used to improve sedation during endoscopy, especially in patients with a history of alcohol or narcotic abuse. We studied whether routine use of droperidol pre-endoscopic retrograde cholangiopancreatography (ERCP) could improve patient and physician satisfaction with sedation. METHODS: Sixty-seven patients undergoing routine ERCP were enrolled in this double-blind placebo-controlled study. Patients were given either parenteral normal saline solution or 5 mg of droperidol 15 minutes before the procedure. After the ERCP, several parameters of procedural sedation were scored on an ordinal scale by the endoscopist, the endoscopy nurse, and the recovered patient. In addition, a follow-up telephone call was made to the patient after 24 hours. RESULTS: The mean procedural room time was similar in the two groups. Nearly 25% less meperidine and diazepam was used in the droperidol-treated patients, making the overall medication cost similar in both groups. The mean recovery room time was 113 minutes for the placebo group and 106 minutes for the droperidol group. Droperidol premedication significantly decreased post-procedure nausea and vomiting, reduced gagging at intubation, and decreased retching during the procedure. Droperidol also improved physician (p = 0.001), nurse (p = 0.001), and patient (p = 0.0001) impressions of overall sedation and decreased the need for physical restraint during the procedure. Droperidol significantly increased the number of patients with no memory of the procedure. CONCLUSION: Droperidol improved overall patient, physician, and nurse satisfaction with sedation during ERCP. It also reduced post-ERCP nausea and vomiting without increasing recovery time or medication cost. Droperidol is recommended for routine pre-ERCP sedation. (Gastrointest Endosc 2000;52:362-6).

EEG changes in 4-week-old lambs in response to castration, tail docking and mulesing.

OBJECTIVE: To interpret changes in EEG in relation to perceived pain of castration, mulesing and docking in lambs. DESIGN: Analysis of covariance (randomised block design) to determine the effects of treatment on eight bandwidths of the EEG frequency spectrum. PROCEDURE: Ninety-eight, 3- to 4-week-old lambs were subjected to one of seven treatments: castration, tail docking, mulesing, ear tagging, sham shearing, formalin injection (to induce lameness) and handling. EEG was recorded for 15 min before treatment, during treatment, and for 15 min after treatment. RESULTS: Consistently lower mean power values across all bandwidths of the EEG were found at the time of mulesing and docking than at handling and shearing (P < 0.01). Formalin injection resulted in lower power values than handling and shearing (P < 0.01). Castration had lower power values than handling and shearing. Similarly, for 15 min after treatment, mulesing and formalin injection had significantly lower power values than handling, shearing, ear tagging and castration (P < 0.05). CONCLUSION: The consistent effects associated with mulesing, docking and castration compared to handling, shearing and ear tagging suggest that mulesing at both the time of treatment and during 15 min after treatment results in a response that is similar to that of induced lameness. Docking and castration result in a response at the time of treatment that is similar to induced lameness and mulesing, but during 15 min after treatment is similar to the non-noxious control treatments. However, the depressing effects on the mean power values are the reverse of that anticipated from a previously developed pain model, highlighting the need for further research to develop this technology to evaluate pain associated with husbandry procedures.

Pharmacoeconomic evaluation of flumazenil for routine outpatient EGD.

BACKGROUND: Flumazenil is a benzodiazepine antagonist indicated for reversal of the sedative effects of benzodiazepines. Previous studies suggest that flumazenil may shorten recovery time after endoscopy, but there are few data on actual recovery room times and charges. METHODS: Fifty patients undergoing routine upper endoscopy were sedated with midazolam alone in the usual titrated manner. Patients were randomized in a double-blind fashion to receive either flumazenil or saline immediately after procedure. Assessments of responsiveness, speech, facial expression, and ptosis (Observer's Assessment of Alertness/Sedation [OAA/S] scale) were made before procedure, immediately after procedure and every 15 minutes thereafter. The patient was discharged from the recovery room when vital signs and OAA/S scale reached preprocedure levels. Recovery room times and charges were recorded. RESULTS: The flumazenil group demonstrated shorter recovery room times and recovery room charges than the placebo group (p < 0.001). The difference in recovery room charges was not statistically different when flumazenil charges were included (p = 0.09). CONCLUSIONS: The routine use of flumazenil after midazolam sedation for upper endoscopy significantly shortened recovery time and charges but did not statistically reduce overall charges.

The diagnosis and work-up of the patient with gastroparesis.

Gastroparesis-or delayed gastric emptying--is associated with upper gastrointestinal symptoms that include early satiety, nausea, vomiting, regurgitation, fullness, and bloating. Gastroparesis should be considered in the diagnosis of a patient with these symptoms after mechanical and structural lesions have been ruled out. This review briefly summarizes gastric motor physiology and discusses the etiology and diagnostic approach to the treatment of a patient with possible gastroparesis. We highlight the methods available to measure gastric motility and describe their relative advantages and disadvantages.

Functional analyses of natural variation in Sp1 binding sites of a TATA-less promoter.

Within the lactate dehydrogenase-B (LdhB) proximal promoter is a region with multiple in vivo footprinted sites that resembles the binding site for the transcription factor SP1. Like many sequences that regulate transcription rate, these Sp1 binding sites are well conserved among species of the teleost fish Fundulus. The only exception is in the northern population of F. heteroclitus, where there are many changes in the Sp1 binding sites. These changes affect footprinting patterns, measures of promoter strength, and are associated with the adaptive increase in Ldh-B transcription rates. Reported here is data that demonstrates that Fundulus hepatocyctes have an SP1-like protein; in comparison to human SP1 protein, it has similar specificity and size and a greater affinity for the consensus Sp1 site. This Fundulus hepatocyte SP1-like protein as well as the human SP1 protein binds the Ldh-B Sp1 sites. Sequence variation in the northern Sp1 region eliminates the "preferred" Sp1 binding site, yet these northern Sp1 sites have significantly greater affinity for the SP1 protein than either the Sp1 sites from southern F. heteroclitus ( approximately 1.6-fold) or the consensus Sp1 site (GGGCGG; approximately 1.8-fold). Furthermore, the Ldh-B Sp1 sites also bind non-SP1 proteins, and the extent of binding is affected by the sequence variation in the proximal promoter. These data suggest that natural variation in Sp1 sites affect binding of transcription factors and may effect a modest change in transcription rates.