Empirical validation of the InVEST water yield ecosystem service model at a national scale.

A variety of tools have emerged with the goal of mapping the current delivery of ecosystem services and quantifying the impact of environmental changes. An important and often overlooked question is how accurate the outputs of these models are in relation to empirical observations. In this paper we validate a hydrological ecosystem service model (InVEST Water Yield Model) using widely available data. We modelled annual water yield in 22 UK catchments with widely varying land cover, population and geology, and compared model outputs with gauged river flow data from the UK National River Flow Archive. Values for input parameters were selected from existing literature to reflect conditions in the UK and were subjected to sensitivity analyses. We also compared model performance between precipitation and potential evapotranspiration data sourced from global- and UK-scale datasets. We then tested the transferability of the results within the UK by additional validation in a further 20 catchments. Whilst the model performed only moderately with global-scale data (linear regression of modelled total water yield against empirical data; slope=0.763, intercept=54.45, R(2)=0.963) with wide variation in performance between catchments, the model performed much better when using UK-scale input data, with closer fit to the observed data (slope=1.07, intercept=3.07, R(2)=0.990). With UK data the majority of catchments showed <10% difference between measured and modelled water yield but there was a minor but consistent overestimate per hectare (86m(3)/ha/year). Additional validation on a further 20 UK catchments was similarly robust, indicating that these results are transferable within the UK. These results suggest that relatively simple models can give accurate measures of ecosystem services. However, the choice of input data is critical and there is a need for further validation in other parts of the world.

Sensitivity analysis of a sediment dynamics model applied in a Mediterranean river basin: global change and management implications.

Climate change and land-use change are major factors influencing sediment dynamics. Models can be used to better understand sediment production and retention by the landscape, although their interpretation is limited by large uncertainties, including model parameter uncertainties. The uncertainties related to parameter selection may be significant and need to be quantified to improve model interpretation for watershed management. In this study, we performed a sensitivity analysis of the InVEST (Integrated Valuation of Environmental Services and Tradeoffs) sediment retention model in order to determine which model parameters had the greatest influence on model outputs, and therefore require special attention during calibration. The estimation of the sediment loads in this model is based on the Universal Soil Loss Equation (USLE). The sensitivity analysis was performed in the Llobregat basin (NE Iberian Peninsula) for exported and retained sediment, which support two different ecosystem service benefits (avoided reservoir sedimentation and improved water quality). Our analysis identified the model parameters related to the natural environment as the most influential for sediment export and retention. Accordingly, small changes in variables such as the magnitude and frequency of extreme rainfall events could cause major changes in sediment dynamics, demonstrating the sensitivity of these dynamics to climate change in Mediterranean basins. Parameters directly related to human activities and decisions (such as cover management factor, C) were also influential, especially for sediment exported. The importance of these human-related parameters in the sediment export process suggests that mitigation measures have the potential to at least partially ameliorate climate-change driven changes in sediment exportation.

Risking your life without a second thought: intuitive decision-making and extreme altruism.

When faced with the chance to help someone in mortal danger, what is our first response? Do we leap into action, only later considering the risks to ourselves? Or must instinctive self-preservation be overcome by will-power in order to act? We investigate this question by examining the testimony of Carnegie Hero Medal Recipients (CHMRs), extreme altruists who risked their lives to save others. We collected published interviews with CHMRs where they described their decisions to help. We then had participants rate the intuitiveness versus deliberativeness of the decision-making process described in each CHMR statement. The statements were judged to be overwhelmingly dominated by intuition; to be significantly more intuitive than a set of control statements describing deliberative decision-making; and to not differ significantly from a set of intuitive control statements. This remained true when restricting to scenarios in which the CHMRs had sufficient time to reflect before acting if they had so chosen. Text-analysis software found similar results. These findings suggest that high-stakes extreme altruism may be largely motivated by automatic, intuitive processes.

Vertical jump in female and male volleyball players: a review of observational and experimental studies.

The main purpose of this article was to review a series of studies (n=32; 24 observational and eight experimental) examining vertical jump (VJ) performances in female and male volleyball players. The main findings of this review are (a) players of better performing teams have higher VJ values; (b) strength and conditioning programs that emphasize plyometric training can increase VJ performance; and (c) it is important to continue conditioning sessions throughout the season in order to maintain VJ performance. Three research limitations associated with the testing protocols and the strength and conditioning programs used in the studies were outlined: (a) the use of multiple testing protocols; (b) lack of experimental studies; and (c) lack of data on the effect of VJ performance on achieving success in actual games. Four recommendations for volleyball and strength and conditioning coaches were given: (a) Plyometric training should be included in the annual training program; (b) Interruptions in the conditioning program during the season should be avoided; (c) Overtraining during the pre-season should be avoided; and (d) VJ performance should be tested throughout the entire season.

Polyethylene mulch modifies greenhouse microclimate and reduces infection of phytophthora infestans in tomato and Pseudoperonospora cubensis in cucumber.

The individual and joint effects of covering the soil with polyethylene mulch before planting and fungicides commonly used by organic growers on tomato late blight (caused by Phytophthora infestans) were studied in three experiments conducted from 2002 to 2005. Application of fungicides resulted in inconsistent and insufficient late blight suppression (control efficacy +/- standard error of 34.5 +/- 14.3%) but the polyethylene mulch resulted in consistent, effective, and highly significant suppression (control efficacy of 83.6 +/- 5.5%) of the disease. The combined effect of the two measures was additive. In a second set of three experiments carried out between 2004 and 2006, it was found that the type of polyethylene mulch used (bicolor aluminized, clear, or black) did not affect the efficacy of late blight suppression (control efficacy of 60.1 to 95.8%) and the differences in the effects among the different polyethylene mulches used were insignificant. Next, the ability of the mulch to suppress cucumber downy mildew (caused by Pseudoperonospora cubensis) was studied in four experiments carried out between 2006 and 2008. The mulch effectively suppressed cucumber downy mildew but the effect was less substantial (control efficacy of 34.9 +/- 4.8%) than that achieved for tomato late blight. The disease-suppressing effect of mulch appeared to come from a reduction in leaf wetness duration, because mulching led to reductions in both the frequency of nights when dew formed and the number of dew hours per night when it formed. Mulching also reduced relative humidity in the canopy, which may have reduced sporulation.

Subgraphs in random networks.

Understanding the subgraph distribution in random networks is important for modeling complex systems. In classic Erdos networks, which exhibit a Poissonian degree distribution, the number of appearances of a subgraph G with n nodes and g edges scales with network size as approximately N(n-g). However, many natural networks have a non-Poissonian degree distribution. Here we present approximate equations for the average number of subgraphs in an ensemble of random sparse directed networks, characterized by an arbitrary degree sequence. We find scaling rules for the commonly occurring case of directed scale-free networks, in which the outgoing degree distribution scales as P(k) approximately k(-gamma). Considering the power exponent of the degree distribution, gamma, as a control parameter, we show that random networks exhibit transitions between three regimes. In each regime, the subgraph number of appearances follows a different scaling law, approximately Nalpha, where alpha=n-g+s-1 for gamma<2, alpha=n-g+s+1-gamma for 2gamma(c), where s is the maximal outdegree in the subgraph, and gamma(c)=s+1. We find that certain subgraphs appear much more frequently than in Erdos networks. These results are in very good agreement with numerical simulations. This has implications for detecting network motifs, subgraphs that occur in natural networks significantly more than in their randomized counterparts.

Pharmacokinetics of clindamycin HCl administered intravenously, intramuscularly and subcutaneously to dogs.

A buffered aqueous solution of clindamycin Hcl (200 mg/mL) was injected intravenously (i.v.) intramuscularly (i.m.) and subcutaneously (s.c.) in a non-randomized, partial cross-over trial involving six male and six female dogs. Blood samples were collected at conventional, predetermined time periods and serum drug concentrations were determined by microbiological assay. Dogs were observed clinically for signs of pain, and activity of serum creatine phosphokinase (CPK) was monitored after i.m. dosing. The i.v. data from five of the dogs best fitted a two-compartment open-system pharmacokinetic model whereas a non-compartment model was most suitable for analysis of the data from the remaining seven dogs. The mean i.v. elimination half-life (t1/2 beta) and the mean residence time (MRT) were 124 and 143 min, respectively. The mean volume of distribution at steady state (Vss) was 0.86 L/kg. Little pain was recorded upon i.m. injection; mean peak serum drug concentration (Cmax) was 4.4 micrograms/mL, the elimination half-life (t1/2el) was 247 min and the calculated bioavailability (F) was 115% of the i.v. dose. Serum CPK activity was elevated to 25-fold the pretreatment level in samples collected 4, 8 and 12 h after i.m. injection. Pain was not recorded after s.c. drug administration; the mean Cmax of 20.8 micrograms/mL was significantly greater than the corresponding value for the i.m. route, and F was 310%. The s.c. route appears to be superior to the i.m. route in terms of local tolerance and serum drug level; a 10 mg/kg SID treatment regimen is suggested for treatment of canine infections due to clindamycin sensitive bacteria.

Pharmacokinetics and penetration of danofloxacin from the blood into the milk of cows.

The single-dose disposition kinetics of danofloxacin were determined in clinically normal lactating cows after intravenous (i.v.) and intramuscular (i.m.) administration of the drug at 1.25 mg/kg. The drug concentrations in blood serum and milk were determined by microbiological assay methods and the data were subjected to kinetic analysis. The mean i.v. and i.m. elimination half-lives (t1/2el) in serum were 54.9 and 135.7 min, respectively. The steady-state volume of distribution (Vss) was 2.04 L/kg. The drug was quickly absorbed after i.m. injection but a 'flip flop' effect was clearly evident and bioavailability was > 100%. Penetration of danofloxacin from blood into milk was rapid and extensive with drug concentrations in milk exceeding those in serum beginning 90-120 min after i.v. and i.m. administration and onwards. Milk danofloxacin concentrations equal to or higher than the minimal inhibitory concentrations (MIC) for pathogenic Gram-negative bacteria and Mycoplasma species were maintained over approximately 24 h. Concentrations greater than the MIC for Staphylococcus aureus were maintained in the milk for 12 h.

Clinical, bacteriological and epidemiological aspects of clinical mastitis in Israeli dairy herds.

A 4-year retrospective study was performed to determine the clinical, bacteriological and epidemiological aspects of acute clinical mastitis in seven Israeli dairy herds. A total of 1124 clinical mastitis cases were detected by abnormal changes in the milk and udder with concurrent decrease of at least 25% in daily milk production. A total of 1190 quarters were affected with clinical mastitis in 1089 cows. The rear quarters had a higher incidence risk (64.7% of quarter cases) than the front quarters. The annual herd-year-incidence varied from 4.2 to 126.8 cases/100 cows/year. The whole-lactation incidence risk (LIR) was 20.8 per 100 lactations. LIR increased from the first to fifth lactation and then decreased. Most clinical mastitis cases were associated with coliform bacteria (60.2% of cases), environmental streptococci (18.6%), coagulase-negative staphylococci (8.7%) and samples from which no bacterial growth was detected (8.1%). Most cases of clinical mastitis occurred in the early stages of lactation, with 51.4% of all cases, 52.3% of coliform cases and 54.6% of environmental streptococci mastitis cases occurring during the first 4 months of lactation. The median days in milk at diagnosis was 118 days. The incidence was lower in the dry summer months. The ratio of peak to low incidence was 1.62 with a calculated peak incidence in January.

Combined effect of ampicillin, colistin and dexamethasone administered intramuscularly to dairy cows on the clinico-pathological course of E. coli-endotoxin mastitis.

The effects of a single intramuscular injection of a drug product containing ampicillin, colistin and dexamethasone, as a suspension in a diester of propylene glycol of medium-chain fatty acids, on the clinico-pathological course of experimental Escherichia coli-endotoxin mastitis was examined in 30 dairy cows. Cows were divided into five groups, six cows per group, and 24 of them were infused with E. coli endotoxin into two quarters of their udders. The drug product was injected at 25,000 IU colistin sulphate, 10.0 mg ampicillin anhydrate and 0.025 mg dexamethasone acetate.kg-1 body weight as follows: Group 2 cows, immediately post-endotoxin infusion (PEI); Group 3 cows, 2 h PEI and, Group 4 cows, 4 h PEI. Group 1 cows were not treated with the product and served as a positive (endotoxin only) control while Group 5 cows were not challenged with endotoxin and were not treated with the product. A clinical mastitis score (CMS) was developed to quantitatively assess the degree of inflammation. Blood biochemistry and hematological parameters were used to monitor the immediate effects of treatment on several conventional inflammatory markers. Milk somatic cell counts (MSCC), milk electrical conductivity and daily milk production were among the parameters used to monitor systemic and local inflammatory reactions. Administration of the drug product immediately PEI and 2 h PEI clearly nullified some of the most severe early systemic reactions to inflammation but the effect of therapy on the local inflammatory markers was not as obvious. Notewhorthy, however, were the effects of the treatment on reducing the duration of elevated quarter MSCC and the increase in the speed of return to pre-endotoxin challenge daily milk production levels.

Relationship between in vitro sensitivity of coliform pathogens in the udder and the outcome of treatment for clinical mastitis.

The relationship between in vitro sensitivity to antimicrobials and the outcome of treatment was studied in 228 cows with coliform mastitis. All the cows were treated with a preparation containing sulphonamide and trimethoprim, and 197 of them were also treated with a non-steroidal anti-inflammatory drug (NSAID). The relationship between in vitro sensitivity to sulphonamide/trimethoprim and recovery was analysed by multivariate logistic regression. The possible confounding effects of treatment with an NSAID, days in lactation, parity, herd, and type of infecting organism were tested. Only treatment with an NSAID had a significant confounding effect and was included in the final statistical model. The recovery rate of the 165 cows infected by coliforms that were sensitive to sulphonamide/trimethoprim (89.1 per cent) was higher than that of the 63 cows infected by coliforms that were resistant to sulphonamide/trimethoprim (74.6 per cent). The odds ratio of recovery for the cases associated with organisms that were sensitive to sulphonamide/trimethoprim relative to the cases associated with organisms that were resistant to sulphonamide/trimethoprim was 2.75, with a 95 per cent confidence from 1.25 to 5.85. The odds ratio of recovery for the cases treated with an NSAID relative to the cases treated with sulphonamide/trimethoprim only was 2.76 with a 95 per cent confidence interval from 1.12 to 6.79.

Efficacy of cefquinome for treatment of cows with mastitis experimentally induced using Escherichia coli.

The efficacy of intramuscularly and intramammarily administered cefquinome was evaluated in experimental Escherichia coli mastitis in dairy cows. Forty-seven multiparous, Israeli Holstein cows in early lactation that produced at least 25 L/d of milk were used, and 400 to 750 cfu of E. coli were infused into two healthy quarters of each cow. Cows were randomly assigned to one of the following treatment groups: 1) 75 mg of cefquinome administered intramammarily three times at 12-h intervals, 2) 75 mg of cefquinome administered intramammarily three times at 12-h intervals and 1 mg/kg of cefquinome administered intramuscularly two times at a 24-h interval, 3) 1 mg/kg of cefquinome administered intramuscularly two times at a 24-h interval, and 4) 75 mg of ampicillin and 200 mg of cloxacillin administered intramammarily three times at 12-h intervals. All cows developed typical signs of acute clinical mastitis by 12 to 16 h postinoculation. Parenteral cefquinome therapy, with or without intramammary cefquinome (groups 2 and 3), significantly improved clinical recovery and return to milk production. The bacteriological cure rates were considerably and significantly higher for cows in the groups treated with cefquinome than for cows in the group treated with ampicillin and cloxacillin. This study supported the efficacy of cefquinome in the treatment of clinical coliform mastitis in dairy cows.

Pharmacokinetics and penetration of marbofloxacin from blood into the milk of cows and ewes.

The single-dose disposition kinetics of marbofloxacin were determined in lactating cows and ewes after intravenous (i.v.) and intramuscular (i.m.) administration of 2, 2.5 and 4 mg/kg. Drug concentrations in blood and milk were determined by microbiological assay and the data were subjected to compartmental and non-compartmental kinetic analyses. In cows, the i.v. serum elimination half-life (t1/2 beta) was approximately 2 h and the i.m. serum elimination half-life (t1/2el) was approximately 3 h. The mean steady-state volume of distribution (Vss) was 1.5 l/kg for the cows and 0.6 l/kg for the ewes. The i.m. availability was nearly 100% for both cows and ewes. Drug penetration into the milk was rapid and extensive with milk marbofloxacin concentrations exceeding those in serum 2 h after administration. Milk drug concentrations equal to or greater than the minimal inhibitory concentrations for the majority of gram-negative udder pathogens were maintained for approximately 12 h after i.v. and i.m. treatment of 2-4 mg/kg. The drug was not detected in milk 24 h after treatment (sensitivity limit of assay = 0.05 microgram/ml).

Pharmacokinetics and penetration of danofloxacin from the blood into the milk of ewes.

The single-dose disposition kinetics of danofloxacin were determined in clinically normal, lactating ewes after intravenous (i.v.) and intramuscular (i.m.) administration of 1.25 mg/kg. The drug concentration in the blood serum and milk were determined by microbiological assay and the data were subjected to compartmental and non-compartmental kinetic analyses. The i.v. and im elimination half-lives in serum (t1/2 beta and t1/2el) were 125.0 +/- 38.6 min and 209.4 +/- 56.3 min, respectively. The steady-state volume of distribution (Vss) was 1.9 +/- 0.7 L/kg. The drug was quickly absorbed after the i.m. injection and the i.m. availability was 100%. Penetration of danofloxacin from the blood into the milk was rapid and extensive with drug concentrations in milk exceeding those in serum beginning 60-90 min after administration and onwards. Milk danofloxacin concentrations equal to or higher than the minimal inhibitory concentrations (MIC) for pathogenic Gram-negative bacteria and Mycoplasma species were maintained over approximately 24 h. Concentrations greater than the MIC for Staphylococcus aureus were maintained in the milk for 12 h.

The anti-inflammatory drugs phenylbutazone and dipyrone in the treatment of field cases of bovine mastitis.

The efficacy of phenylbutazone vs. dipyrone for the treatment of acute clinical mastitis were compared in a clinical trial. All cows were treated with 20 g sulfadiazine and 4 g trimethoprim i.m. upon diagnosis and half dosage once daily thereafter. In addition, the NSAIDs treated cows received once daily either 4 g phenylbutazone or 20 g dipyrone i.m. for the duration of the antimicrobial therapy. In all treatment groups the major causative organisms were coliforms. Recovery rates for the controls, the phenylbutazone and dipyrone treatment groups were 81.8%, 89.4% and 86.6%, respectively. Recovery was evaluated by the logistic regression analysis, the odds ratios (OR) and their 95% confidence interval (CI) of treatment success for phenylbutazone and dipyrone treatments relative to the control treatment were calculated. Odds ratio of recovery was high for phenylbutazone (OR = 2.42; CI = 0.98-5.96; P = 0.054) as well as for dipyrone (OR = 1.71; CI = 0.98-3.00; P = 0.060), demonstrating a strong trend towards improved recovery in NSAID groups. The odds of treatment failure for the phenylbutazone group relative to the dipyrone group was 0.71 with 95% CI of 0.28-1.78. Clearly no significant difference could be demonstrated between phenylbutazone and dipyrone in this field trial.

Isolation and antimicrobial susceptibility of obligate anaerobic bacteria recovered from the uteri of dairy cows with retained fetal membranes and postparturient endometritis.

The uteri of 77 postparturient dairy cows were sampled. Samples were cultured aerobically and anaerobically, and the nature of bacterial growth was identified. A mixed aerobic and anaerobic bacterial infection was found in 55% of the samples. Actinomyces pyogenes was the predominant aerobic species; it was found in 70% of the samples, whereas Bacteroides melaninogenicus was the most frequent anaerobic species isolated. Altogether, 16 species belonging to the genus Bacteroides were identified with variable frequencies. It appears that more than one Bacteroides species colonizes the uterus of a given cow postpartum. The minimal inhibitory concentrations (MICs) of clindamycin, metronidazole, tetracycline and ciprofloxacin for 83 anaerobic isolates were determined. All isolates were susceptible to clindamycin (MIC90 of 0.064 microgram/ml) and all but two to metronidazole. Susceptibility to ciprofloxacin was variable, with a bimodal distribution of MIC values. The MIC of tetracycline for 90% of the isolates was > 256 micrograms/ml.

Effect of water deprivation on the disposition kinetics of enrofloxacin in camels.

Concentrations of enrofloxacin equivalent activity were determined (by microbiological assay) in the serum of normal camels and camels at the end of a 14-day water-deprivation period following single intravenous (i.v.), intramuscular (i.m.) and subcutaneous (s.c.) administrations at 2.5 mg/kg. Also, normal camels were given an oral drench of the drug at 5 mg/kg. Pharmacokinetic variables were determined using compartmental and non-compartmental analytical methods. Camels lost on average 12.5% of body weight at the end of the water-deprivation period. The disposition kinetics of i.v. administered drug in normal and water-deprived camels were very similar. The t1/2 beta was 3.0-3.5 h; MRT was 4.0-4.5 h; Vc was 0.3 L/kg; Vss was 1.0 L/kg and ClB was 4.0-4.6 mL/min/kg. The effect of water deprivation on the rate of drug absorption and elimination after i.m. administration was inconsistent, and there was also a large degree of variability in the normal animals that precluded statistical significance. After s.c. administration, the mean absorption half-life (t1/2abs) in the water-deprived camels was significantly longer than in the normal camels. Systemic availability (F) was similar in both normal and water-deprived camels after i.m. dosing but was significantly greater (P < 0.05) in normal camels (0.92 compared with 0.65 in water-deprived camels) after s.c. treatment. In normal camels, urinary recovery at 12 h after i.v. and s.c. dosing was 25% and 15%, respectively, and the extent of serum protein binding ranged between 1.7% at 1.8 micrograms/mL and 24% at 0.33 microgram/mL. The drug was not detected in serum after oral administration. Serum and milk enrofloxacin equivalent activities were determined after i.v. (one camel) and i.m. (one camel) drug administration. Serum drug concentrations were consistently higher than in the milk. The AUCmilk/AUCserum ratios were 0.27 and 0.39 after i.v. and i.m. drug administration, respectively. An i.m. or s.c. treatment regimen of 2.5 mg/kg q.12 h is suggested for clinical and bacteriological efficacy trials with enrofloxacin in normally hydrated and dehydrated camels.

Tilmicosin antibacterial activity and pharmacokinetics in cows.

The minimal inhibitory concentration (MIC) of tilmicosin for 90% of 112 Staphylococcus aureus isolates from the bovine udder was 0.78 microgram/mL and 149 of 164 (90.8%) other gram-positive udder pathogens were inhibited by tilmicosin concentrations < 3.12 micrograms/mL. The MIC of the drug for 19 of 22 S. aureus isolates was < 0.78 microgram/mL when the test was conducted using Mueller-Hinton (MH) agar or MH agar containing 7.5% skimmed milk. Acute cardiac toxicity followed intravenous (i.v.) injection of the drug at 10 mg/kg to 3 cows, but animals appeared clinically normal within 30 min after treatment. The pharmacokinetics of i.v.-administered tilmicosin is typical for the macrolide class of antibiotics, i.e. low serum drug concentrations and a large volume of distribution (> 2.0 L/kg). The elimination half-life (t1/2 beta) values for 3 cows were 46.4, 56.0 and 72.8 min. The drug was administered subcutaneously (s.c.) to 5 cows at 10 mg/kg; the elimination half-life (t1/2el) was 4.18 +/- 0.55 h and the mean s.c. bioavailability was 22%. Rapid and extensive penetration of tilmicosin from blood into milk, and slow elimination from the milk were among the characteristic kinetic features of the drug after i.v. and s.c. administration. Tilmicosin was injected s.c. at 10 mg/kg once to 9 cows after the last milking of lactation; dry udder secretion samples were collected daily for 11 consecutive days and assayed microbiologically. Concentrations of drug > 0.78 microgram/mL were found in the secretion for 8-9 days after dosing. Systemic side-effects were not observed after s.c. drug administration.

Serum and milk concentrations of apramycin in lactating cows, ewes and goats.

A 20% solution of apramycin was administered intravenously (i.v.) and intramuscularly (i.m.) to lactating cows with clinically normal and acutely inflamed udders, to lactating ewes with normal or subclinically infected, inflamed udders and i.v. to lactating goats with normal udders. The i.v. disposition kinetics of apramycin was very similar in cows, ewes and goats. The elimination half-life was approximately 2 h and the steady-state volume of distribution was 1.26-1.45 L/kg. The absorption rate of the drug from the i.m. injection site was rapid, the i.m. bioavailability was 60-70% and the mean elimination half-life was 265 min in cows and 145.5 min in ewes. The binding percentage of apramycin to serum protein was low (< 22.5%). Concentrations of apramycin in milk produced by clinically normal mammary glands of cows, ewes and goats were consistently lower than in serum; the kinetic value AUCmilk/AUCserum was < 0.32. Drug penetration into the milk from the acutely inflamed quarters of cows was extensive; mastitis milk Cmax values were more than tenfold greater than the Cmax in normal milk. On the other hand, the drug had limited access to the milk produced by subclinically infected inflamed half-udders of ewes.