Socioeconomic assessment of the relevance of a community-based goat breeding project in smallholding systems.

In the last decade, community-based animal breeding programs have gained attention for the genetic improvement of small ruminants in the tropics. Nevertheless, implementing such programs remains challenged by the issue of smallholders' participation. To shed light on this issue of participation, a goat genetic improvement project has been assessed for its socioeconomic relevance through participatory methods, taking account of goat multifunctionality. We quantified the gross margins per flock and per animal as indicators of viability. We assessed then the correspondence between the goat functions defined through a proportional piling tool with the relative share of these functions in the gross revenue. For that purpose, 160 smallholders were surveyed and 77 among them were monitored for one year. A cluster analysis of factors linked to the dynamic of goat farming identified three groups of farmers. The first group gathered farmers with the smallest goat flocks, who were goat oriented in the future. Their sustainable participation in goat breeding project was impeded by the excessive sales of goats. The second group involved farmers with the highest farm size, who planned to buy cattle to replace part of their goats. The third group included farmers who were members of the project with the largest goat flocks. This group emphasized the importance of goat for their future but showed weak abilities to manage large flocks. The gross margin per animal was the highest in the third group. The relative importance of goat functions as defined through participatory tools did not correspond to the relative share of these functions in the composition of the gross revenue from goats. Participatory tools and economic calculation then appear as complementary to understand farmers' priorities. Consolidating breeders' associations and supporting farmers to diversify their sources of income are two ways proposed here to ensure an enabling environment to goat husbandry and farmers' well-being.

Tolerance to bovine clinical mastitis: Total, direct, and indirect milk losses.

The objectives of this paper were to estimate direct and indirect milk losses associated with mastitis. Indirect losses, linked to indirect tolerance, are mediated by the increase in milk somatic cell count (SCC) in response to bacterial infection. Direct losses, linked to weak direct tolerance, are not mediated by the increase in SCC. So far, studies have evaluated milk loss associated with clinical mastitis without considering both components, which may lead to biased estimates of their sum; that is, the total loss in milk. A total of 43,903 test-day records on milk and SCC from 3,716 cows and 5,858 lactations were analyzed with mediation mixed models and health trajectories to estimate the amount of direct, indirect, and total milk losses after adjustment for known and potentially unmeasured (sensitivity analyses) confounding factors. Estimates were formalized under the counterfactual causal theory of causation. In this study, milk losses were mostly mediated by an increase in SCC. They were highest in the first month of lactation, when SCC were highest. Milk losses were estimated at 0.5, 0.8, and 1.1 kg/d in first, second, and third and greater parity, respectively. Two phases described how changes in milk were associated with changes in SCC: on average, one occurred before and one after the day preceding the clinical diagnosis. In both phases, changes in milk were estimated at 1 mg/d per 103 cells/mL. After adjusting for known confounders, cow effect accounted for 20.7 and 64.2% of the variation in milk in the first and second phases, respectively. This suggests that deviations from the resilient path were highest during the second phase of inflammation and that selection for cows more tolerant to mastitis is feasible. As discussed herein, epigenetic regulation of macrophage polarization may contribute to the variation in milk observed in the second phase.

Effect of genetic European taurine ancestry on milk yield of Ankole-Holstein crossbred dairy cattle in mixed smallholders system of Burundi highlands.

Different breeding systems associated with specific bovine genetic resources have coexisted in Burundi. To prepare for the development of a national action plan for the improvement of bovine genetic resources in Burundi, we aimed at performing genetic characterization of Ankole and Ankole × European crossbred individuals and assessing the effect of European ancestry on milk productivity of cows kept under the mixed crops livestock system. To that end, we genotyped 37 Ankole and 138 crossbred individuals on 42 636 SNPs and combined these genotypes with those from 21 cattle breeds, representative of the bovine genetic diversity. We also measured milk yield not suckled and estimated suckled milk. Given the results, we confirmed the indicine × African taurine admixed origin of the Ankole in Burundi and showed that crossbred individuals present a high proportion of European ancestry (i.e. 57% on average). As the proportion of European ancestry increased, milk yield increased by 0.03 ± 0.01 l/day, at a lower extent than expected. We also observed that breeders were unable to correctly evaluate the European proportion in their livestock. Our results may provide useful information for objective dairy breeding in Burundi. As an example, an ex-situ conservation program of Ankole within the framework of value chains is proposed as an accompanying strategy to improve the sustainability of the crossbreeding program.

A strategy to estimate the rate of recruitment of inflammatory cells during bovine intramammary infection under field management.

BACKGROUND: In most infectious diseases, among which bovine mastitis, promptness of the recruitment of inflammatory cells (mainly neutrophils) in inflamed tissues has been shown to be of prime importance in the resolution of the infection. Although this information should aid in designing efficient control strategies, it has never been quantified in field studies. METHODS: Here, a system of ordinary differential equations is proposed that describes the dynamic process of the inflammatory response to mammary pathogens. The system was tested, by principal differential analysis, on 1947 test-day somatic cell counts collected on 756 infected cows, from 50 days before to 50 days after the diagnosis of clinical mastitis. Cell counts were log-transformed before estimating recruitment rates. RESULTS: Daily rates of cellular recruitment was estimated at 0.052 (st. err. = 0.005) during health. During disease, an additional cellular rate of recruitment was estimated at 0.004 (st. err. = 0.001) per day and per bacteria. These estimates are in agreement with analogous measurements of in vitro neutrophil functions. CONCLUSIONS: Results suggest the method is adequate to estimate one of the components of innate resistance to mammary pathogens at the individual level and in field studies. Extension of the method to estimate components of innate tolerance and limits of the study are discussed.

Mediation analysis to estimate direct and indirect milk losses associated with bacterial load in bovine subclinical mammary infections.

Milk losses associated with mastitis can be attributed to either effects of pathogens per se (i.e. direct losses) or to effects of the immune response triggered by the presence of mammary pathogens (i.e. indirect losses). Test-day milk somatic cell counts (SCC) and number of bacterial colony forming units (CFU) found in milk samples are putative measures of the level of immune response and of the bacterial load, respectively. Mediation models, in which one independent variable affects a second variable which, in turn, affects a third one, are conceivable models to estimate direct and indirect losses. Here, we evaluated the feasibility of a mediation model in which test-day SCC and milk were regressed toward bacterial CFU measured at three selected sampling dates, 1 week apart. We applied this method on cows free of clinical signs and with records on up to 3 test-days before and after the date of the first bacteriological samples. Most bacteriological cultures were negative (52.38%), others contained either staphylococci (23.08%), streptococci (9.16%), mixed bacteria (8.79%) or were contaminated (6.59%). Only losses mediated by an increase in SCC were significantly different from null. In cows with three consecutive bacteriological positive results, we estimated a decreased milk yield of 0.28 kg per day for each unit increase in log2-transformed CFU that elicited one unit increase in log2-transformed SCC. In cows with one or two bacteriological positive results, indirect milk loss was not significantly different from null although test-day milk decreased by 0.74 kg per day for each unit increase of log2-transformed SCC. These results highlight the importance of milk losses that are mediated by an increase in SCC during mammary infection and the feasibility of decomposing total milk loss into its direct and indirect components.

A Bayesian path analysis to estimate causal effects of bazedoxifene acetate on incidence of vertebral fractures, either directly or through non-linear changes in bone mass density.

BACKGROUND/AIMS: Bone mass density values have been related with risk of vertebral fractures in post-menopausal women. However, bone mass density is not perfectly accurate in predicting risk of fracture, which decreases its usefulness as a surrogate in clinical trials. We propose a modeling framework with three interconnected parts to improve the evaluation of bone mass density accuracy in forecasting fractures after treatment. METHODS: The modeling framework includes: (1) a piecewise regression to describe non-linear temporal BMD changes more accurately than crude percent changes, (2) a structural equation model to analyze interdependencies among vertebral fractures and their potential risk factors in preference to regression techniques that consider only directional associations, and (3) a counterfactual causal interpretation of the direct and indirect relationships between treatment and occurrence of vertebral fractures. We apply the methods to BMD repeated measurements from a study of the effect of bazedoxifene acetate on incident vertebral fractures in three different geographical regions. RESULTS: We made four observations: (1) bone mass density changes varied largely across participants, (2) baseline age and body mass index influenced baseline bone mass density that, in turn, had an effect on prevalent fractures, (3) direct and/or indirect effects of bazedoxifene acetate on incident fractures were different across regions, and (4) estimates of indirect effects were sensible to the presence of post-treatment unmeasured confounders. In one region, around 40% of the bazedoxifene acetate effect on the occurrence of fracture is explained by its effect on bone mass density. Under the counterfactual approach, these 40% represent the average difference in the occurrence of fracture observed for untreated individuals when their bone mass density values are set at the value under bazedoxifene acetate versus under placebo. CONCLUSIONS: Computational methods are available to evaluate and interpret the surrogacytic capability of a biomarker of a primary outcome.

Mediation analysis to estimate direct and indirect milk losses due to clinical mastitis in dairy cattle.

Milk losses associated with mastitis can be attributed to either effects of pathogens per se (i.e., direct losses) or effects of the immune response triggered by intramammary infection (indirect losses). The distinction is important in terms of mastitis prevention and treatment. Regardless, the number of pathogens is often unknown (particularly in field studies), making it difficult to estimate direct losses, whereas indirect losses can be approximated by measuring the association between increased somatic cell count (SCC) and milk production. An alternative is to perform a mediation analysis in which changes in milk yield are allocated into their direct and indirect components. We applied this method on data for clinical mastitis, milk and SCC test-day recordings, results of bacteriological cultures (Escherichia coli, Staphylococcus aureus, Streptococcus uberis, coagulase-negative staphylococci, Streptococcus dysgalactiae, and streptococci other than Strep. dysgalactiae and Strep. uberis), and cow characteristics. Following a diagnosis of clinical mastitis, the cow was treated and changes (increase or decrease) in milk production before and after a diagnosis were interpreted counterfactually. On a daily basis, indirect changes, mediated by SCC increase, were significantly different from zero for all bacterial species, with a milk yield decrease (ranging among species from 4 to 33g and mediated by an increase of 1000 SCC/mL/day) before and a daily milk increase (ranging among species from 2 to 12g and mediated by a decrease of 1000 SCC/mL/day) after detection. Direct changes, not mediated by SCC, were only different from zero for coagulase-negative staphylococci before diagnosis (72g per day). We concluded that mixed structural equation models were useful to estimate direct and indirect effects of the presence of clinical mastitis on milk yield.

Evaluating somatic cell scores with a Bayesian Gaussian linear state-space model.

Because accurate characterization of health state is important for managing dairy herds, we propose to validate the use of a linear state-space model (LSSM) for evaluating monthly somatic cell scores (SCSs). To do so, we retrieved SCS from a dairy database and collected reports on clinical mastitis collected in 20 farms, during the period from January 2008 to December 2011 in the Walloon region of Belgium. The dependent variable was the SCS, and the independent variables were the number of days from calving, year of calving and parity. The LSSM also incorporated an error-free underlying variable that described the trend across time as a function of previous clinical and subclinical status. We computed the mean sum of squared differences between observed SCS and median values of the posterior SCS distribution and constructed the receiver operating characteristic (ROC) curve for SCS thresholds going from 0 to 6. Our results show SCS estimates are close to observed SCS and area under the ROC curve is higher than 90%. We discuss the meaning of the parameters in light of our current knowledge of the disease and propose methods to incorporate, in LSSM, this knowledge often expressed in the form of ordinary differential equations.

Prevalence and risk factors for cardiac diseases in a hospital-based population of 3,434 horses (1994-2011).

BACKGROUND: Risk factors for cardiac diseases in horses have not been explored in a large population of animals. OBJECTIVES: To describe risk factors for various cardiac diseases in a hospital-based population of horses. ANIMALS: Files of 3,434 horses admitted at the Internal Medicine Department of the Liege Equine Teaching Hospital between 1994 and 2011 were reviewed and of those, 284 were categorized as having moderate-to-severe cardiac disease. METHODS: Observational study. After calculating prevalence for each cardiac disease, we tested whether breed (chi-square test) or sex, age, body weight (BW), and other cardiac diseases (logistic regressions) were risk factors (p < .05 significant). RESULTS: Mitral regurgitation (MR, 4.4%), atrial fibrillation (AF, 2.3%), aortic regurgitation (AR, 2.1%), and tricuspid regurgitation (TR, 1.7%) were the most common cardiac abnormalities detected. Determinants were male sex and increasing age for AR (OR = 2.03, CI = 1.07-4.94), racehorses breed and middle-age for TR (OR = 4.36; CI = 1.10-17.24), and high BW for AF (OR = 3.54; CI = 1.67-7.49). MR was the most common valvular disease associated with AF, clinically important ventricular arrhythmia, pulmonary regurgitation (PR), and congestive heart failure (CHF). TR was also associated with AF, PR, and CHF; AR was not associated with CHF. CONCLUSIONS AND CLINICAL IMPORTANCE: Several previously suspected risk factors for a variety of equine cardiac diseases are statistically confirmed and other risk factors are highlighted in the studied hospital-based population. These observations should be taken into account in health and sport's monitoring of horses presenting predisposing factors.

Sensitivity and specificity of blood leukocyte counts as an indicator of mortality in horses after colic surgery.

The objectives of this study were to describe and relate perioperative changes in blood leukocyte counts to the outcome of surgical colic horses, determine a cut-off value in the early postoperative period to obtain an indicator of the outcome, and compare the obtained value to a validation population of horses. Fifty-three horses undergoing colic surgery were included in the descriptive part of the study. Total leukocyte counts were performed before, during and serially after surgery. A receiver operating characteristic analysis was performed on the leukocyte counts of 45 of these horses to determine a cut-off value for the outcome. The results obtained were validated on a second set of 50 horses that underwent colic surgery in similar conditions. The kinetics of blood leukocytes in survivors was higher than in non-survivors during the first days. Non-survivor horses were more likely to have at least one blood leukocyte count ≤ 3.9 × 10(3)/mm(3) between 28 and 60 hours after surgery than survivor horses. This cut-off value was confirmed in the validation population. These results suggest that routine values of blood leukocyte counts can be used as an additional prognostic indicator after colic surgery alongside other predictors previously associated with the outcome.

Association of breeding conditions with prevalence of osteochondrosis in foals.

Osteochondrosis (OC) is the most common developmental orthopaedic disease in horses and represents a major problem to the horse industry. The complete mechanism of this multifactorial disease is not yet elucidated, but it is accepted that OC lesions are the result of intrinsic genetic and external factors. The aim of the present work was to evaluate the relationship between breeding management and OC. Breeding conditions were recorded, and a radiological examination was performed in 223 foals. Feeding practice and housing management were analysed in a multivariate model to determine risk factors for OC in three periods: gestation, birth to weaning and weaning to one-year-old. The major breakthrough of this study is the significant relationship between OC development and (1) the maternal nutrition during gestation and (2) the type of housing of the foals during their first year. It appears that mares fed with concentrates during gestation are more likely to produce foals that are subsequently affected by OC compared with other mares (P<0.05). Foals housed exclusively at pasture until one year of age are significantly less affected than foals exclusively housed in box or, alternatively, in box and at pasture (P<0.05). These results underline the role of the energy metabolism and the level of exercise in the aetiologic process of the disease, and help to develop preventive strategies during the crucial period of gestation to one year of age of the foal.

Effects of short-chain fructooligosaccharides on growth performance of preruminant veal calves.

This study was conducted to evaluate the effects of 2 different daily doses of short-chain fructooligosaccharides (scFOS), a prebiotic ingredient, added to a calf milk replacer on growth performance, carcass characteristics, and fecal concentrations of short-chain fatty acids of preruminant veal calves. In total, 112 male Prim'Holstein calves, between 8 and 10d of age, were randomized in this study according to their body weight and were bred until the age of 168 d. They were fed a calf milk replacer containing 5% soluble wheat proteins as well as cereal-based pellets, the composition of which was adapted to cover the needs of the animals throughout the study. After 2 wk of adaptation, the calf milk replacer was supplemented or not supplemented with a daily dose of 3 or 6g of scFOS. Growth performance of calves, as measured by body weight, cold carcass weight, feed intake, average daily gain, and feed conversion ratio, was recorded and feces samples were taken to evaluate short-chain fatty acid concentrations. The inclusion of wheat proteins in milk replacer did not negatively affect the growth performance of calves in comparison with general standards. The addition of scFOS in the milk reduced the feed conversion ratio of veal calves in a dose-dependent manner and tended to increase the carcass weight. A general trend was observed for an increased production of total short-chain fatty acids in time, but scFOS decreased acetate proportion to the benefit of butyrate proportion. These data suggest that inclusion of scFOS in the calf milk replacer allowed the growth performance of preruminant calves to be enhanced, possibly via a modification of the activities of microbial fermentation.

A structural equation model to evaluate direct and indirect factors associated with a latent measure of mastitis in Belgian dairy herds.

In dairy cattle, many farming practices have been associated with occurrence of mastitis but it is often difficult to disentangle the causal threads. Structural equation models may reduce the complexity of such situations. Here, we applied the method to examine the links between mastitis (subclinical and clinical) and risk factors such as herd demographics, housing conditions, feeding procedures, milking practices, and strategies of mastitis prevention and treatment in 345 dairy herds from the Walloon region of Belgium. During the period January 2006 to October 2007, up to 110 different herd management variables were recorded by two surveyors using a questionnaire for the farm managers and during a farm visit. Monthly somatic cell counts of all lactating cows were collected by the local dairy herd improvement association. Structural equation models were created to obtain a latent measure of mastitis and to reduce the complexity of the relationships between farming practices, between indicators of herd mastitis and between both. Robust maximum likelihood estimates were obtained for the effects of the herd management variables on the latent measure of herd mastitis. Variables associated directly (p<0.05) with the latent measure of herd mastitis were the addition of urea in the rations; the practices of machine stripping, of pre-and post-milking teat disinfection; the presence of cows with hyperkeratotic teats, of cubicles for housing and of dirty liners before milking; the treatment of subclinical cases of mastitis; and the age of the herd (latent variable for average age and parity of cows, and percentage of heifers in the herd). Treatment of subclinical mastitis was also an intermediate in the association between herd mastitis and post-milking teat disinfection. The study illustrates how structural equation model provides information regarding the linear relationships between risk factors and a latent measure of mastitis, distinguishes between direct relationships and relationships mediated through intermediate risk factors, allows the construction of latent variables and tests the directional hypotheses proposed in the model.

Mid-infrared prediction of lactoferrin content in bovine milk: potential indicator of mastitis.

Lactoferrin (LTF) is a milk glycoprotein favorably associated with the immune system of dairy cows. Somatic cell count is often used as an indicator of mastitis in dairy cows, but knowledge on the milk LTF content could aid in mastitis detection. An inexpensive, rapid and robust method to predict milk LTF is required. The aim of this study was to develop an equation to quantify the LTF content in bovine milk using mid-infrared (MIR) spectrometry. LTF was quantified by enzyme-linked immunosorbent assay (ELISA), and all milk samples were analyzed by MIR. After discarding samples with a coefficient of variation between 2 ELISA measurements of more than 5% and the spectral outliers, the calibration set consisted of 2499 samples from Belgium (n = 110), Ireland (n = 1658) and Scotland (n = 731). Six statistical methods were evaluated to develop the LTF equation. The best method yielded a cross-validation coefficient of determination for LTF of 0.71 and a cross-validation standard error of 50.55 mg/l of milk. An external validation was undertaken using an additional dataset containing 274 Walloon samples. The validation coefficient of determination was 0.60. To assess the usefulness of the MIR predicted LTF, four logistic regressions using somatic cell score (SCS) and MIR LTF were developed to predict the presence of mastitis. The dataset used to build the logistic regressions consisted of 275 mastitis records and 13 507 MIR data collected in 18 Walloon herds. The LTF and the interaction SCS × LTF effects were significant (P < 0.001 and P = 0.02, respectively). When only the predicted LTF was included in the model, the prediction of the presence of mastitis was not accurate despite a moderate correlation between SCS and LTF (r = 0.54). The specificity and the sensitivity of models were assessed using Walloon data (i.e. internal validation) and data collected from a research herd at the University of Wisconsin - Madison (i.e. 5886 Wisconsin MIR records related to 93 mastistis events - external validation). Model specificity was better when LTF was included in the regression along with SCS when compared with SCS alone. Correct classification of non-mastitis records was 95.44% and 92.05% from Wisconsin and Walloon data, respectively. The same conclusion was formulated from the Hosmer and Lemeshow test. In conclusion, this study confirms the possibility to quantify an LTF indicator from milk MIR spectra. It suggests the usefulness of this indicator associated to SCS to detect the presence of mastitis. Moreover, the knowledge of milk LTF could also improve the milk nutritional quality.

MT1-MMP protects breast carcinoma cells against type I collagen-induced apoptosis.

As invading breast carcinoma cells breach their underlying basement membrane, they become confronted with a dense three-dimensional reactive stroma dominated by type I collagen. To develop metastatic capabilities, invading tumor cells must acquire the capacity to negotiate this novel microenvironment. Collagen influences the fate of epithelial cells by inducing apoptosis. However, the mechanisms used by invading tumor cells to evade collagen-induced apoptosis remain to be defined. We demonstrate that membrane type-1 matrix metalloproteinase (MT1-MMP/MMP-14) confers breast cancer cells with the ability to escape apoptosis when embedded in a collagen gel and after orthotopic implantation in vivo. In the absence of MMP-14-dependent proteolysis, type I collagen triggers apoptosis by inducing the expression of the pro-apoptotic Bcl-2-interacting killer in luminal-like breast cancer cells. These findings reveal a new mechanism whereby MMP-14 activity promotes tumor progression by circumventing apoptosis.

Comparison of four refractometers for the investigation of the passive transfer in beef calves.

BACKGROUND: Failure of passive transfer (FPT) in beef calves can be detected by refractometry. Nevertheless, different models of refractometers are available, and few studies compare them for the detection of FPT. OBJECTIVES: To compare the accuracy of 4 different refractometers for measuring serum total protein concentrations in comparison with results obtained by the biuret method and, based on the serum IgG threshold of 1,600 mg/mL, to determine, for each refractometer, the optimal serum protein concentration's lowest threshold for successful passive transfer. ANIMALS: One hundred and eight healthy beef calves, 3-8 days of age. METHODS: Observational study. The concentrations of serum total proteins were determined with 4 different models of refractometers and compared with the biuret method by a Bland-Altman statistical method. The optimal serum protein concentration's lowest threshold for successful passive transfer was determined for each refractometer by receiver operating characteristic (ROC) analysis. In addition, the serum immunoglobulin G (IgG) concentration was compared with the serum gamma-glutamyl transferase (γ-GT) activity and with the total immunoglobulin concentration. RESULTS: The refractometric measurements were highly correlated with those obtained by the biuret method. Serum total protein concentration threshold values of 56, 58, 54, and 56 g/L were found respectively for the Atago, Atago ATC, Wolf ATC, and digital ATC refractometers. Immunoglobulins were highly correlated with IgG, whereas γ-GT only reflected colostrum uptake by the calf. CONCLUSIONS AND CLINICAL IMPORTANCE: All refractometers could be used for the assessment of passive transfer using their individual serum protein concentration threshold.

Relationship between arthroscopic joint evaluation and the levels of Coll2-1, Coll2-1NO(2), and myeloperoxidase in the blood and synovial fluid of horses affected with osteochondrosis of the tarsocrural joint.

OBJECTIVE: To evaluate the levels of plasmatic and synovial Coll2-1, Coll2-1NO(2) and myeloperoxidase (MPO) in horses with osteochondral lesions of the tarsocrural joint and to investigate how these levels relate to arthroscopic findings of inflammation and degeneration. MATERIALS AND METHODS: Venous blood and synovial fluid samples were collected from 63 horses presented for arthroscopic removal of osteochondral fragments in the tarsocrural joint. Prior to removal of the osteochondral fragment, an exploration of the joint was performed and an inflammatory and degenerative score was determined. The blood and synovial levels of Coll2-1, Coll2-1NO(2) and MPO were also measured. The effects of the arthroscopic evaluation (inflammatory and degenerative classes) on the blood and synovial markers were evaluated using a linear model (GLM procedure), and correlations between biochemical markers in the blood and synovial fluid and the arthroscopic evaluation (inflammatory and degenerative classes) were established (Pearson's correlations). RESULTS: Significantly higher levels of Coll2-1 were detected in synovial fluid of higher degenerative classes. There was a significant correlation between the degenerative score and the synovial levels of Coll2-1 (r=0.27). According to the logistic regression model, there was a significant effect of the degenerative class on synovial levels of Coll2-1. CONCLUSIONS: Coll2-1 correlates well with the degenerative state of tarsocrural joints as evaluated by arthroscopy. This marker can therefore be classified as a burden-of-disease marker in the assessment of joint disease in horses.

A hidden Markov model to predict early mastitis from test-day somatic cell scores.

In many countries, high somatic cell scores (SCS) in milk are used as an indicator for mastitis because they are collected on a routine basis. However, individual test-day SCS are not very accurate in identifying infected cows. Mathematical models may improve the accuracy of the biological marker by making better use of the information contained in the available data. Here, a simple hidden Markov model (HMM) is described mathematically and applied to SCS recorded monthly on cows with or without clinical mastitis to evaluate its accuracy in estimating parameters (mean, variance and transition probabilities) under healthy or diseased states. The SCS means were estimated at 1.96 (s.d. = 0.16) and 4.73 (s.d. = 0.71) for the hidden healthy and infected states, and the common variance at 0.83 (s.d. = 0.11). The probability of remaining uninfected, recovering from infection, getting newly infected and remaining infected between consecutive test days was estimated at 78.84%, 60.49%, 11.70% and 15%, respectively. Three different health-related states were compared: clinical stages observed by farmers, subclinical cases defined for somatic cell counts below or above 250 000 cells/ml and infected stages obtained from the HMM. The results showed that HMM identifies infected cows before the appearance of clinical and subclinical signs, which may critically improve the power of the studies on the genetic determinants of SCS and reduce biases in predicting breeding values for SCS.

Higher sensitivity of Adamts12-deficient mice to tumor growth and angiogenesis.

ADAMTS (a disintegrin and metalloproteinase domain with thrombospondin motifs) constitute a family of endopeptidases related to matrix metalloproteinases. These proteases have been largely implicated in tissue remodeling and angiogenesis associated with physiological and pathological processes. To elucidate the in vivo functions of ADAMTS-12, we have generated a knockout mouse strain (Adamts12(-/-)) in which Adamts12 gene was deleted. The mutant mice had normal gestations and no apparent defects in growth, life span and fertility. By applying three different in vivo models of angiogenesis (malignant keratinocyte transplantation, Matrigel plug and aortic ring assays) to Adamts12(-/-) mice, we provide evidence for a protective effect of this host enzyme toward angiogenesis and cancer progression. In the absence of Adamts-12, both the angiogenic response and tumor invasion into host tissue were increased. Complementing results were obtained by using medium conditioned by cells overexpressing human ADAMTS-12, which inhibited vessel outgrowth in the aortic ring assay. This angioinhibitory effect of ADAMTS-12 was independent of its enzymatic activity as a mutated inactive form of the enzyme was similarly efficient in inhibiting endothelial cell sprouting in the aortic ring assay than the wild-type form. Altogether, our results show that ADAMTS-12 displays antiangiogenic properties and protect the host toward tumor progression.