The Pharmacokinetic/Pharmacodynamic (PK/PD) relationship of antimicrobial drugs (AMD) for surgical prophylaxis has been poorly studied, hampering evidence-based decision making around AMD dosing and ...timing. Our objective is to use PK/PD principles to inform (1) the timing of administration and (2) the interval for re-administration of AMD used peri-operatively in dogs. Raw plasma concentrations of cefazolin, cefuroxime, cefalexin, amoxicillin and ampicillin were retrieved from original intravenous studies performed in dogs. E. coli and methicillin-susceptible staphylococci were identified as possible intraoperative contaminants and their epidemiological cut-offs (ECOFF) were retrieved from the EUCAST database. Individual PK data were refitted with non-linear mixed effect models (Phoenix®). We performed Monte Carlo simulation to compute i) the 95th percentile of time of peak concentration in the peripheral compartment (informing timing between administration and first incision) and ii) the duration for which at least 90% of dogs maintain a free plasma concentration above ECOFF (informing timing of re-administration: 1.5–4 h). Cefazolin (22–25 mg/kg), cefuroxime (20 mg/kg), cefalexin (15 mg/kg) and amoxicillin (16.7 mg/kg) reached peak peripheral concentrations within 30 min, but ampicillin (20 mg/kg) required 82 min, respectively. For methicillin-susceptible staphylococci, cefazolin and cefuroxime require re-administration every 2 h, whereas cefalexin and both amoxicillin and ampicillin can be readministered every 3 and 4 h, respectively. For E. coli, only cefazolin provided adequate perioperative coverage with 2-hourly administration, where cefuroxime and cefalexin failed uniformly. Alternatively, ampicillin and amoxicillin (critically ill dogs) may cover E. coli contaminations, but only if readministered every 1.5 h. These PK-derived conclusions provide a rationale for perioperative AMD administration timing.
•Pharmacokinetics (PK) can guide peri-operative antimicrobial prophylaxis in dogs.•Cefazolin, cefuroxime, cephalexin, amoxicillin and ampicillin PK were modeled.•For staphylococci, all drugs provided adequate coverage for at least 2 h.•For E. coli, only cefazolin provided adequate coverage with 2-hourly redosing.•Ampicillin and amoxicillin (sick dogs) cover E. coli if readministered every 1.5 h.
Milk fatty acid composition is gaining interest in the Danish dairy industry both to develop new dairy products and as a management tool. To be able to implement milk fatty acid (FA) composition in ...the breeding program, it is important to know the correlations with the traits in the breeding goal. To estimate these correlations, we measured milk fat composition in Danish Holstein (DH) and Danish Jersey (DJ) cattle breeds using mid-infrared spectroscopy. Breeding values were estimated for specific FA and for groups of FA. Correlations with the estimated breeding values (EBV) underlying the Nordic Total Merit index (NTM) were calculated within breed. For both DH and DJ, we showed that FA EBV had moderate correlations with the NTM and production traits. For both DH and DJ, the correlation of FA EBV and NTM were in the same direction, except for C16:0 (0 in DH, 0.23 in DJ). A few correlations differed between DH and DJ. The correlation between claw health index and C18:0 was negative in DH (−0.09) but positive in DJ (0.12). In addition, some correlations were not significant in DH but were significant in DJ. The correlations between udder health index and long-chain FA, trans FA, C16:0, and C18:0 were not significant in DH (−0.05 to 0.02), but were significant in DJ (−0.17, −0.15, 0.14, and −0.16, respectively). For both DH and DJ, the correlations between FA EBV and nonproduction traits were low. This implies that it is possible to breed for a different fat composition in the milk without affecting the nonproduction traits in the breeding goal.
The objective of this study was to assess the genetic variability of the detailed fatty acid (FA) profiles of Danish Holstein (DH) and Danish Jersey (DJ) cattle populations. We estimated genetic ...parameters for 11 FA or groups of FA in milk samples from the Danish milk control system between May 2015 and October 2016. Concentrations of different FA and FA groups in milk samples were measured by mid-infrared spectroscopy. Data used for parameter estimation were from 132,732 first-parity DH cows and 21,966 first-parity DJ cows. We found the highest heritabilities for test day measurements in both populations for short-chain FA (DH = 0.16; DJ = 0.16) and C16:0 (DH = 0.14; DJ = 0.16). In DH, the highest heritabilities were also found for saturated FA and monounsaturated FA (both populations: 0.15). Genetic correlations between the fatty acid traits showed large differences between DH and DJ for especially short-chain FA with the other FA traits measured. Furthermore, genetic correlations of total fat with monounsaturated FA, polyunsaturated FA, short-chain FA, and C16:0 differed markedly between DH and DJ populations. In conclusion, we found genetic variation in the mid-infrared spectroscopy-predicted FA and FA groups of the DH and DJ cattle populations. This finding opens the possibility of using genetic selection to change the FA profiles of dairy cattle.
This study presents and validates a detection and monitoring model for mastitis based on automated frequent sampling of online cell count (OCC). Initially, data were filtered and adjusted for sensor ...drift and skewed distribution using ln-transformation. Acceptable data were passed on to a time-series model using double exponential smoothing to estimate level and trends at cow level. The OCC levels and trends were converted to a continuous (0–1) scale, termed elevated mastitis risk (EMR), where values close to zero indicate healthy cow status and values close to 1 indicate high risk of mastitis. Finally, a feedback loop was included to dynamically request a time to next sample, based on latest EMR values or errors in the raw data stream. The estimated EMR values were used to issue 2 types of alerts, new and (on-going) intramammary infection (IMI) alerts. The new alerts were issued when the EMR values exceeded a threshold, and the IMI alerts were issued for subsequent alerts. New alerts were only issued after the EMR had been below the threshold for at least 8d. The detection model was evaluated using time-window analysis and commercial herd data (6 herds, 595,927 milkings) at different sampling intensities. Recorded treatments of mastitis were used as gold standard. Significantly higher EMR values were detected in treated than in contemporary untreated cows. The proportion of detected mastitis cases using new alerts was between 28.0 and 43.1% and highest for a fixed sampling scheme aiming at 24h between measurements. This was higher for IMI alerts, between 54.6 and 89.0%, and highest when all available measurements were used. The lowest false alert rate of 6.5 per 1,000 milkings was observed when all measurements were used. The results showed that a dynamic sampling scheme with a default value of 24h between measurements gave only a small reduction in proportion of detected mastitis treatments and remained at 88.5%. It was concluded that filtering of raw data combined with a time-series model was effective in detecting and monitoring mastitis status in dairy cows when based on IMI alerts, and by using a dynamically adjusting sampling scheme almost full performance was still obtainable. However, results were less desirable when based on new alerts most likely because of the used gold standard for mastitis, which may not necessarily reflect the onset of and IMI case in contrast to a new alert.
Aims/hypothesis
Soluble CD163 (sCD163) was recently identified as a strong risk marker for developing type 2 diabetes. We hypothesised that sCD163 independently associates with insulin resistance.
...Methods
This cross-sectional study includes 234 participants: 96 with type 2 diabetes, 34 with impaired glucose tolerance (IGT) and 104 with normal glucose tolerance (NGT), matched for sex and BMI. Glucose-lowering medication was paused for 1 week before plasma samples were obtained for determination of sCD163 and other inflammatory and metabolic variables. Insulin resistance was estimated by homeostasis model assessment of insulin resistance (HOMA-IR).
Results
Concentrations of sCD163 were 1.95 mg/l (0.63–6.97) in individuals with type 2 diabetes, 1.64 mg/l (0.58–4.19) in those with IGT, and 1.48 mg/l (0.48–4.11) (median range) in those with NGT (
p
< 0.0001). In univariate analyses, sCD163 correlated significantly with HOMA-IR (
R
= 0.44), insulin (
R
= 0.41), glucose (
R
= 0.30), triacylglycerol (
R
= 0.29) and HDL-cholesterol (
R
= −0.34) (all
p
< 0.0001). All but glucose remained significant when adjusting for age, sex, BMI and glycaemic group. In univariate regression analyses, HOMA-IR was associated with sCD163, C-reactive protein (CRP), TNF-α and IL-6 (all
p
≤ 0.0001). An increase of 50% in sCD163 resulted in an estimated increase in HOMA-IR of 36% (95% CI 26, 48;
p
< 0.0001). In multiple linear regression analyses, sCD163 (
p
= 0.001) and CRP (
p
= 0.01) remained independent predictors of HOMA-IR, whereas TNF-α and IL-6 did not.
Conclusions/interpretation
Macrophage-specific sCD163 was strongly associated with insulin resistance independently of TNF-α and other predictors. Moreover, sCD163 was associated with well-known variables of the metabolic syndrome.
Abstract
We report the first asteroseismic results obtained with the Hertzsprung Stellar Observations Network Group Telescope from an extensive high-precision radial-velocity observing campaign of ...the subgiant
μ
Herculis. The data set was collected during 215 nights in 2014 and 2015. We detected a total of 49 oscillation modes with
l
values from zero to three, including some
l
= 1 mixed modes. Based on the rotational splitting observed in
l
= 1 modes, we determine a rotational period of 52 days and a stellar inclination angle of 63°. The parameters obtained through modeling of the observed oscillation frequencies agree very well with independent observations and imply a stellar mass between 1.11 and 1.15
M
⊙
and an age of
Gyr. Furthermore, the high-quality data allowed us to determine the acoustic depths of the He
ii
ionization layer and the base of the convection zone.
The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes.
In recent years, genomic selection (GS) has accelerated ...genetic gain in dairy cattle breeds worldwide. Despite the evident genetic progress, several dairy populations have also encountered challenges such as heightened inbreeding rates and reduced effective population sizes. The challenge has been to find a balance between achieving substantial genetic gain while managing genetic diversity within the population, thereby mitigating the negative effects of inbreeding depression. This study aims to elucidate the impact of GS on pedigree and genomic rates of inbreeding (ΔF) and coancestry (ΔC) in Nordic Jersey (NJ) and Holstein (NH) cattle populations. Furthermore, key genetic metrics, including the generation interval (L), effective population size (Ne), and future effective population size (FNe) were assessed between 2 time periods, before and after GS, and across distinct animal cohorts in both breeds: females, bulls, and approved semen-producing bulls (AI-sires). Analysis of ΔF and ΔC revealed distinct trends across the studied periods and animal groups. Notably, there was a consistent increase in yearly ΔF for most animal groups in both breeds. An exception was observed in NH AI-sires, which demonstrated a slight decrease in yearly ΔF. Moreover, NJ displayed minimal changes in yearly ΔC between the periods, whereas NH exhibited elevated ΔC values across all animal groups. Particularly striking was the substantial increase in yearly ΔC within the NH female population, surging from 0.02% to 0.39% between the periods. Implementation of GS resulted in a reduction of the generation interval across all animal cohorts in both NJ and NH breeds. However, the extent of reduction was more pronounced in males compared with females. This reduction in generation interval influenced generational changes in ΔF and ΔC. Bulls and AI-sires of both breeds exhibited reduced generational ΔF between periods, in contrast to females that demonstrated an opposing pattern. Between the periods, NJ maintained a relatively stable Ne (29.4 before and 30.3 after GS), whereas NH experienced a notable decline from 54.3 to 42.8. Female groups in both breeds displayed a negative Ne trend, whereas males demonstrated either neutral or positive Ne developments. Regarding FNe, NJ exhibited positive FNe development with an increase from 40.7 to 57.2. The opposite was observed in NH, where FNe decreased from 198.8 to 42.7. In summary, it was evident that the genomic methods could detect differences between the populations and changes in ΔF and ΔC more efficiently than pedigree methods. Implementation of GS yielded positive outcomes within the NJ population regarding the rate of coancestry but the opposite was observed with NH. Moreover, analysis of ΔC data hints at the potential to decrease future ΔF through informed mating strategies. Conversely, NH faces more pressing concerns, even though ΔF remains comparatively modest in contrast to what has been observed in other Holstein populations. These findings underscore the necessity of genomic control of inbreeding and coancestry with strategic changes in the Nordic breeding schemes for dairy to ensure long-term sustainability in the forthcoming years.
The objectives of this study were 1) to estimate costs related to 5 different pathogen-specific mastitis traits (susceptibility to different pathogens causing mastitis in dairy cattle) and unspecific ...mastitis, and 2) to compare selection differentials for an udder health index consisting of 5 different pathogen-specific mastitis traits and lactation average somatic cell count from 5 to 170 d after first calving (LASCC170) with another index consisting of 1 unspecific mastitis trait and LASCC170. Economic values were estimated for mastitis caused by Staphylococcus aureus, Streptococcus dysgalactiae, Escherichia coli, coagulase-negative staphylococci, and Streptococcus uberis using a stochastic simulation model (SimHerd IV). Mastitis incidences for SimHerd IV were from incidences of mastitis treatments in primiparous Danish Holstein cows calving in 2007. Estimated costs ranged from €149 to €570 per mastitis case and were highest for contagious pathogens such as Staph. aureus and coagulase-negative staphylococci and lowest for Strep. dysgalactiae and Strep. uberis. The value for unspecific mastitis was €231 per case. Selection differentials (in €) were estimated for 4 different selection indices, including 1) unspecific mastitis, 2) unspecific mastitis and LASCC170, 3) 5 pathogen-specific mastitis traits and unspecific residual mastitis (unspecific mastitis treatments minus mastitis treatments caused by the 5 pathogens), and 4) as index 3 including LASCC170. The breeding goal was identical to selection index 3. Mastitis data from primiparous cows calving from 1998 to 2008 were used to estimate genetic parameters of the mastitis traits using linear models and AI-REML algorithm. These parameters were used for construction of the selection index equations. For the selection indices, information sources were measurements of mastitis treatments and LASCC170 from 50, 80, or 130 daughters of a bull as well as measurements of mastitis treatments from 1,000 progeny of the bull's sire and 1,000 daughters of his maternal grandsire. Differences in selection differentials were marginal among the 4 indices. Without considering LASCC170, the selection differential of an unspecific mastitis index was €0.4 (<1%) better than that of a pathogen-specific index. On the other hand, the selection differential of the pathogen-specific index was €0.3 (<1%) better than that of an unspecific index when LASCC170 was included in the indices. Reliabilities of the selection indices were 0.62 to 0.67 (80 daughters) and were proportional to the selection differential. Changing the number of daughters to 50 or 130 did not change ranking of the indices. Heritabilities of the pathogen-specific traits were very low (h2=0.005–0.021) compared with unspecific mastitis (h2=0.062), which may limit the selection differential of the pathogen-specific index.
Surgical antimicrobial prophylaxis (SAP) is widely used to reduce the risk of surgical site infections (SSI), but there is uncertainty as to what the proportion of SSI reduction is. Therefore, it is ...difficult for surgeons to properly weigh the costs, risks and benefits for individual patients when deciding on the use of SAP, making it challenging to promote antimicrobial stewardship in primary practice settings. The objective of this study was to map the veterinary evidence focused on assessing the effect of SAP on SSI development and in order to identify surgical procedures with some research evidence and possible knowledge gaps. In October 2021 and December 2022, Scopus, CAB Abstracts, Web of Science Core Collection, Embase and MEDLINE were systematically searched. Double blinded screening of records was performed to identify studies in companion animals that reported on the use of SAP and SSI rates. Comparative data were available from 34 out of 39123 records screened including: eight randomised controlled trials (RCT), 23 cohort studies (seven prospective and 16 retrospective) and three retrospective case series representing 12476 dogs and cats in total. Extracted data described peri- or post-operative SAP in nine, and 25 studies, respectively. In the eight RCTs evaluating SAP in companion animals, surgical procedure coverage was skewed towards orthopaedic stifle surgeries in referral settings and there was large variation in SAP protocols, SSI definitions and follow-up periods. More standardized data collection and agreement of SSI definitions is needed to build stronger evidence for optimized patient care.
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•There was a substantial lack of evidence for antimicrobial prophylaxis practices•There was a general lack of details in the reporting of antimicrobial (AM) usage•There was a lack of studies on common surgical procedures seen in primary practice•There was great variation in surgical site infection (SSI) definitions applied•Standards for AM and SSI outcomes is highly needed for future comparative studies
Mastitis in dairy cows is an unavoidable problem and genetic variation in recovery from mastitis, in addition to susceptibility, is therefore of interest. Genetic parameters for susceptibility to and ...recovery from mastitis were estimated for Danish Holstein-Friesian cows using data from automatic milking systems equipped with online somatic cell count measuring units. The somatic cell count measurements were converted to elevated mastitis risk, a continuous variable on a (0–1) scale indicating the risk of mastitis. Risk values >0.6 were assumed to indicate that a cow had mastitis. For each cow and lactation, the sequence of health states (mastitic or healthy) was converted to a weekly transition: 0 if the cow stayed within the same state and 1 if the cow changed state. The result was 2 series of transitions: one for healthy to diseased (HD, to model mastitis susceptibility) and the other for diseased to healthy (DH, to model recovery ability). The 2 series of transitions were analyzed with bivariate threshold models, including several systematic effects and a function of time. The model included effects of herd, parity, herd-test-week, permanent environment (to account for the repetitive nature of transition records from a cow) plus two time-varying effects (lactation stage and time within episode). In early lactation, there was an increased risk of getting mastitis but the risk remained stable afterwards. Mean recovery rate was 45% per lactation. Heritabilities were 0.07 posterior mean of standard deviations (PSD) = 0.03 for HD and 0.08 (PSD = 0.03) for DH. The genetic correlation between HD and DH has a posterior mean of −0.83 (PSD = 0.13). Although susceptibility and recovery from mastitis are strongly negatively correlated, recovery can be considered as a new trait for selection.
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