A new TCAD simulation method for direct CMOS electron detectors optimization.

A custom CMOS image sensor hardened by design is characterized in a transmission electron microscope, with the aim to extract basic parameters such as the quantum efficiency, the modulation transfer function and finally the detective quantum efficiency. In parallel, a new methodology based on the combination of Monte Carlo simulation of electron distributions and TCAD simulations is proposed and performed on the same detector, and for the first time the basic parameters of a direct CMOS electron detector are extracted thanks to the TCAD. The methodology is validated by means of the comparison between experimental and simulation results. This simulation method may be used for the development of future electron detectors.

Erratum to "A parallel evaluation of 5 indirect cost-effective methods for assessing failure of passive immunity transfer in neonatal calves" (JDS Commun. 1:10-14).

[This corrects the article DOI: 10.3168/jdsc.2019-17931.].

A parallel evaluation of 5 indirect cost-effective methods for assessing failure of passive immunity transfer in neonatal calves.

The aim of this study was to evaluate the diagnostic accuracy of 5 indirect methods that may be used in veterinary practices to assess the success of maternal immunoglobulins transfer in neonatal calves. Blood samples (n = 245) were collected from 2- to 6-d-old calves. Serum immunoglobulin concentrations were determined by radial immunodiffusion. Serum total protein and albumin concentrations and γ-glutamyl transferase activity were determined by veterinary practitioners using their own biochemistry analyzer. Globulin concentration was calculated. Veterinary practitioners were also asked to assess serum total protein using a digital Brix refractometer (%Brix) and an optical refractometer (g/L). Test sensitivity (Se) and specificity (Sp) were calculated using radial immunodiffusion as the reference standard, with failure of transfer of passive immunity defined as IgG <10.0 g/L. Receiver operating characteristics curves were created and optimal cutoff values for each of the 5 indirect measurement methods were selected based on the maximization of the Youden's J statistic. In this study, Globulin concentration yielded the highest accuracy to identify failure of transfer of passive immunity (Se = 89.4%; Sp = 89.3% at 34 g/L). For %Brix, the optimal combination of Se and Sp was at 8.4% Brix (Se = 86.5% and Sp = 83.8%). The use of an optical refractometer was associated with the lowest diagnostic accuracy (Se = 69.7% and Sp = 81.6% at 52 g/L). For γ-glutamyl transferase activity, the optimal cut-points were different for 2- to 3-d-old calves (Se = 87.5% and Sp = 87.8% at 393 IU/L) or 4- to 6-d-old calves (Se = 90.0% and Sp = 86.4% at 254 IU/L). Because it does not require any specialized laboratory equipment, digital Brix refractometer can be a valuable and inexpensive tool for on-farm use, to help producers and veterinary practitioners in their calf health management programs.

Accuracy of paratuberculosis diagnostic tests in small ruminants: protocol for a systematic review and meta-analysis.

Paratuberculosis is a worldwide infectious disease caused by Mycobacterium avium ssp. paratuberculosis (MAP). Various ruminant species can be affected by the disease, and the diagnosis of the disease is challenging in the absence of a gold standard test. The aim of this systematic review protocol is to determine the accuracy of the direct and indirect diagnostic tests for MAP infection with a special focus on sheep and goats.

Economic assessment of an emerging disease: the case of Schmallenberg virus in France.

Schmallenberg virus (SBV) was first detected in 2011 in Germany and then in France in 2012. This study simulates the production of different ruminant systems in France and estimates, through partial budget analyses, the economic cost of SBV at the farm level, under two disease scenarios (a high-impact and low-impact scenario). A partial budget is used to evaluate the financial effect of incremental changes, and includes only resources or production that will be changed. In the high-impact scenario, the estimated impact of SBV ranged from €23 to €43 per cow per year and €19 to €37 per ewe per year. In the low-impact scenario, it was approximately half (for cows) or one-third (for ewes) of this amount. These financial impacts represent 0.6% to 63% of the gross margin, depending on the chosen scenario and the livestock system being considered. The impacts of SBV come mainly from: the extra costs from purchasing and raising replacement heifers and losses in milk production (dairy cows); the losses in calf or lamb production (beef systems and meat sheep); and the losses in milk production and from unsold replacement lambs (dairy sheep). The use of integrated production and economic models enabled the authors to estimate the cost of SBV and to tackle the problem of scarce data, which is a difficulty for most emerging diseases, by their very nature. It also allowed the authors to develop an accurate disease impact assessment for several production systems, over a short time span. Extrapolating from this economic assessment to predict the scenario in coming years depends on the immunity period of the disease and the length of the production cycles.

Le virus de Schmallenberg a été détecté pour la première fois en 2011 en Allemagne, puis en France en 2012. Les auteurs présentent une étude de simulation de plusieurs systèmes de production de ruminants en France, dont l'objectif était d'estimer, à partir d'analyses budgétaires partielles, les coûts économiques du virus de Schmallenberg à l'échelle des exploitations, sous deux scénarios différents (hypothèses d'un fort impact et d'un faible impact de la maladie, respectivement). Une analyse budgétaire partielle sert à évaluer les conséquences financières d'un changement graduel et ne prend en compte que les modifications effectives en termes de ressources et de production. Dans l'hypothèse d'un impact fort de la maladie, l'impact annuel estimé du virus de Schmallenberg variait de 23 à 43 euros par vache et de 19 à 37 euros par brebis. Dans l'hypothèse d'un impact faible, l'impact annuel était deux fois moindre chez les vaches et trois fois moindre chez les brebis que dans la première hypothèse. Ces impacts financiers représentent 0,6 % à 63 % de la marge brute en fonction du scénario choisi et du système de production. Les impacts du virus de Schmallenberg découlent principalement des coûts supplémentaires induits par l'achat et le maintien de génisses de remplacement et d'une baisse de la production de lait (vaches laitières), des pertes de veaux ou d'agneaux (bovins et ovins de boucherie), d'une baisse de la production de lait et du coût des agnelles de remplacement invendues (brebis laitières). L'utilisation de modèles intégrant les aspects économiques et les données de production a permis aux auteurs d'estimer le coût du virus de Schmallenberg malgré la pénurie de données, s'attaquant ainsi à une difficulté inhérente à la plupart des maladies émergentes. Cela leur a également permis d'effectuer une évaluation précise de l'impact sanitaire dans plusieurs systèmes de production, sur une durée courte. La possibilité d'extrapoler à partir de cette évaluation économique un scénario pour les années à venir dépend de la période d'immunité vis-à-vis de la maladie et de la durée des cycles de production.

El virus de Schmallenberg fue detectado por primera vez en 2011 en Alemania y ulteriormente en 2012 en Francia. Los autores describen un estudio en el que se simularon distintos sistemas de producción de rumiantes en Francia y se estimó, con análisis presupuestarios parciales, el coste económico que entrañaría para una explotación el virus de Schmallenberg en dos hipotéticas situaciones sanitarias (una situación con efectos profundos y otra con efectos leves). El análisis presupuestario parcial sirve para evaluar los efectos económicos de cambios graduales, e incluye únicamente aquellos recursos y aspectos de la producción que experimentarán cambios. En la hipótesis de efectos profundos, el impacto estimado de la infección por el virus de Schmallenberg oscilaba entre 23 y 43 euros anuales por vaca y entre 19 y 37 euros anuales por oveja hembra. La hipótesis de efectos leves deparaba importes de aproximadamente la mitad (en el caso de las vacas) o un tercio (en el de las ovejas). Este impacto económico representa del 0,6% al 63% del margen bruto, dependiendo de la hipótesis elegida y del sistema productivo de que se trate. Los efectos de la infección por el virus de Schmallenberg se concretan básicamente en: los costos suplementarios derivados de adquirir y criar vaquillas de sustitución y de obtener una menor producción de leche (vacas lecheras); las pérdidas de terneros o corderos (sistemas de bovino u ovino cárnicos); y los costos derivados de la menor producción de leche y de no vender las corderas de sustitución (ovejas lecheras). El uso de modelos que integran los factores productivos y económicos sirvió a los autores para estimar el costo del virus de Schmallenberg a pesar de la escasez de datos, que, por la propia naturaleza de las enfermedades emergentes, es una dificultad común a la mayoría de ellas. También les permitió evaluar con exactitud el impacto de la enfermedad en distintos sistemas productivos en un breve lapso de tiempo. La realización de extrapolaciones a partir de esta evaluación económica para pronosticar la situación en años venideros depende del periodo de inmunidad respecto de la enfermedad y de la duración de los ciclos productivos.

Epidemiological analysis of reproductive performances and kitten mortality rates in 5,303 purebred queens of 45 different breeds and 28,065 kittens in France.

Reproduction management and performances are evaluated in the feline species only through a limited number of animals and studies. Our objective was to provide reference figures in purebred cats, from a large-scale sample. Data were collected from an online software dedicated to cattery management (Breeding Management System®, BMS, Royal Canin, Aimargues, France). Information was recorded on a voluntary basis by French breeders between 2011 and 2014. Data were anonymously transferred for analysis. A total of 9,063 oestrous periods (in contact with a male) from 5,303 queens (45 breeds) were recorded from 1,521 breeders. Most matings (70.1%) occurred during increasing day length periods. The mean age at mating (±SD) was 2.7 ± 1.6 years for queens and 2.9 ± 1.9 years for tomcats. Pregnancy rate (based on breeders declaration) was 85.2%. Among queens declared pregnant, 8.4% failed to maintain pregnancy. Globally, 78% of the mated females gave birth to 28,065 kittens within 7,075 L. Mean litter size was 4.0 ± 1.9 kittens among which 8.5% were stillborn. Neonatal and paediatric mortality rate was 8.2%. In total, 16.0% of kittens born died before weaning. The results of this study are based on the largest feline database ever analysed. The figures collected can thus be used as reference to define average reproductive performances in numerous breeds for cat breeders. Further analysis will identify factors influencing reproductive performances and early mortality in the feline species.

Invited review: Improving neonatal survival in small ruminants: science into practice.

Neonatal mortality in small ruminant livestock has remained stubbornly unchanging over the past 40 years, and represents a significant loss of farm income, contributes to wastage and affects animal welfare. Scientific knowledge about the biology of neonatal adaptation after birth has been accumulating but does not appear to have had an impact in improving survival. In this paper, we ask what might be the reasons for the lack of impact of the scientific studies of lamb and kid mortality, and suggest strategies to move forward. Biologically, it is clear that achieving a good intake of colostrum, as soon as possible after birth, is crucial for neonatal survival. This provides fuel for thermoregulation, passive immunological protection and is involved in the development of attachment between the ewe and lamb. The behaviour of the lamb in finding the udder and sucking rapidly after birth is a key component in ensuring sufficient colostrum is ingested. In experimental studies, the main risk factors for lamb mortality are low birthweight, particularly owing to poor maternal nutrition during gestation, birth difficulty, litter size and genetics, which can all be partly attributed to their effect on the speed with which the lamb reaches the udder and sucks. Similarly, on commercial farms, low birthweight and issues with sucking were identified as important contributors to mortality. In epidemiological studies, management factors such as providing assistance with difficult births, were found to be more important than risk factors associated with housing. Social science studies suggest that farmers generally have a positive attitude to improving neonatal mortality but may differ in beliefs about how this can be achieved, with some farmers believing they had no control over early lamb mortality. Facilitative approaches, where farmers and advisors work together to develop neonatal survival strategies, have been shown to be effective in achieving management goals, such as optimising ewe nutrition, that lead to reductions in lamb mortality. We conclude that scientific research is providing useful information on the biology underpinning neonatal survival, such as optimal birthweights, lamb vigour and understanding the importance of sufficient colostrum intake, but the transfer of that knowledge would benefit from an improved understanding of the psychology of management change on farm. Developing tailored solutions, on the basis of adequate farm records, that make use of the now substantial body of scientific literature on neonatal mortality will help to achieve lower neonatal mortality.

Short communication: performance of a blocking antibody ELISA bulk-tank milk test for detection of dairy sheep flocks exposed to border disease virus.

The aim of this study was to investigate the test characteristics of a blocking antibody ELISA applied to bulk-tank milk (BTM) samples for the detection of dairy sheep flocks positive for antibodies to border disease virus. In 161 flocks recruited in 2009 and 2010, the antibody inhibition percentage (AIP) in BTM was compared with the prevalence estimate of antibody-positive ewes obtained from an age-representative sample of 45 milking ewes. A strong negative exponential relationship (R(2)=0.89) was found between AIP in BTM and seroprevalence level. Using receiver operating characteristic analysis, the best AIP decision threshold in BTM to discriminate between low (<10%) and high (≥10%) antibody-positive flocks was 65%. Diagnostic performance estimates based on observed seroprevalence levels and Monte Carlo simulations showed that this threshold value was associated with high sensitivity and specificity (91.9±5.5% and 95.9±1.6%, respectively), whereas the 80% decision threshold recommended in dairy cows yielded lower specificity (83.6±2.0%). Results obtained from the same flocks during 2 subsequent milking campaigns showed that the 65% AIP cut-off value was associated with fewer false-positive results and is preferred. Testing of BTM samples could be a powerful tool in inferring border disease virus seroprevalence in a flock and in Pestivirus control schemes in dairy sheep flocks.

Identification of seven haplotypes of the caprine PrP gene at codons 127, 142, 154, 211, 222 and 240 in French Alpine and Saanen breeds and their association with classical scrapie.

In sheep, susceptibility to scrapie is mainly influenced by polymorphisms of the PrP gene. In goats, there are to date few data related to scrapie susceptibility association with PrP gene polymorphisms. In this study, we first investigated PrP gene polymorphisms of the French Alpine and Saanen breeds. Based on PrP gene open reading frame sequencing of artificial insemination bucks (n=404), six encoding mutations were identified at codons 127, 142, 154, 211, 222 and 240. However, only seven haplotypes could be detected: four (GIH(154)RQS, GIRQ(211)QS, GIRRK(222)S and GIRRQP(240)) derived from the wild-type allele (G(127)I(142)R(154)R(211)Q(222)S(240)) by a single-codon mutation, and two (S(127)IRRQP(240) and GM(142)RRQP(240)) by a double-codon mutation. A case-control study was then implemented in a highly affected Alpine and Saanen breed herd (90 cases/164 controls). Mutations at codon 142 (I/M), 154 (R/H), 211 (R/Q) and 222 (Q/K) were found to induce a significant degree of protection towards natural scrapie infection. Compared with the baseline homozygote wild-type genotype I(142)R(154)R(211)Q(222)/IRRQ goats, the odds of scrapie cases in IRQ(211)Q/IRRQ and IRRK(222)/IRRQ heterozygous animals were significantly lower [odds ratio (OR)=0.133, P<0.0001; and OR=0.048, P<0.0001, respectively]. The heterozygote M(142)RRQ/IRRQ genotype was only protective (OR=0.243, P=0.0186) in goats also PP(240) homozygous at codon 240. However, mutated allele frequencies in French Alpine and Saanen breeds were low (0.5-18.5 %), which prevent us from assessing the influence of all the possible genotypes in natural exposure conditions.

Dynamics and genetics of PrPSc placental accumulation in sheep.

Placentae from scrapie-affected ewes are an important source of contamination. This study confirmed that scrapie-incubating ewes bearing susceptible genotypes could produce both abnormal prion protein (PrPSc)-positive and -negative placentae, depending only on the PRP genotype of the fetus. The results also provided evidence indicating that scrapie-incubating ARR/VRQ ewes may be unable to accumulate prions in the placenta, whatever the genotype of their progeny. Multinucleated trophoblast cells appeared to play a key role in placental PrPSc accumulation. PrPSc accumulation began in syncytiotrophoblasts before disseminating to uninucleated trophoblasts. As these result from trophoblast/uterine epithelial cell fusion, syncytiotrophoblast cells expressed maternal and fetal PrPC, whilst uninucleated trophoblast cells only expressed fetal PrPC. In ARR/VRQ scrapie-infected ewes, expression of the ARR allele by syncytiotrophoblasts appeared to prevent initiation of PrPSc placental deposition. The absence of prions in affected ARR/VRQ sheep placentae reinforces strongly the interest in ARR selection for scrapie control.

PrPSc accumulation in myocytes from sheep incubating natural scrapie.

Because variant Creutzfeldt-Jakob disease (vCJD) in humans probably results from consumption of products contaminated with tissue from animals with bovine spongiform encephalopathy, whether infectious prion protein is present in ruminant muscles is a crucial question. Here we show that experimentally and naturally scrapie-affected sheep accumulate the prion protein PrP(Sc) in a myocyte subset. In naturally infected sheep, PrP(Sc) is detectable in muscle several months before clinical disease onset. The relative amounts of PrP(Sc) suggest a 5,000-fold lower infectivity for muscle as compared to brain.