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Objective: Older patients with cancer value functional outcomes as much as survival, but surgical studies lack functional recovery (FR) data. The value of a standardized frailty assessment has been confirmed, yet it's infrequently utilized due to time restrictions into everyday practice. The multicenter GOSAFE study was designed to (1) evaluate the trajectory of patients' quality of life (QoL) after cancer surgery (2) assess baseline frailty indicators in unselected patients (3) clarify the most relevant tools in predicting FR and clinical outcomes. This is a report of the study design and baseline patient evaluations. Materials & Methods: GOSAFE prospectively collected a baseline multidimensional evaluation before major elective surgery in patients (70 years) from 26 international units. Short-/mid-/Iong-term surgical outcomes were recorded with QoL and FR data. Results: 1003 patients were enrolled in a 26-month span. Complete baseline data were available for 977(97.4%). Median age was 78 years (range 70-94); 52.8% males. 968(99%) lived at home, 51.6% without caregiver. 54.4% had 3 medications, 5.9% none. Patients were dependent (ADL < 5) in 7.9% of the cases. Frailty was either detected by G8 = 2(37.4%), TUG > 20 s (5.2%) or ASAIII-IV (48.8%). Major comorbidities (CACI > 6) were detected in 36%; 20.9% of patients had cognitive impairment according to Mini-Cog. Conclusion: The GOSAFE showed that frailty is frequent in older patients undergoing cancer surgery. QoL and FR, for the first time, are going to be primary outcomes of a real-life observational study. The crucial role of frailty assessment is going to be addressed in the ability to predict postoperative outcomes and to correlate with QoL and FR. (C) 2019 Elsevier Ltd. All rights reserved.

Coccidiosis in poultry, caused by protozoan parasites of the genus Eimeria, is an intestinal disease with substantial economic impact. With the use of anticoccidial drugs under public and political pressure, and the comparatively higher cost oflive-attenuated vaccines, an attractive complementary strategy for control is to breed chickens with increased resistance to Eimeria parasitism. Prior infection with Eimeria maxima leads to complete immunity against challenge with homologous strains, but only partial resistance to challenge with antigenically diverse heterologous strains. We investigate the genetic architecture of avian resistance to E. maxima primary infection and heterologous strain secondary challenge using White Leghorn populations of derived inbred lines, C.B12 and 15I, known to differ in susceptibility to the parasite. An intercross population was infected with E. maxima Houghton (H) strain, followed three weeks later by E. maxima Weybridge (W) strain challenge, while a backcross population received a single E. maxima W infection. The phenotypes measured were parasite replication (counting faecal oocyst output or qPCR for parasite numbers in intestinal tissue), and intestinal lesion score (gross pathology, scale 0-4), and for the backcross only, serum interleukin 10 (IL-10) levels. Birds were genotyped using a high density genome-wide DNA array (600K, Affymetrix). Genome-wide association study (GWAS) located associations on chromosomes 1, 2, 3 and 5 following primary infection in the backcross population, and a suggestive association on chromosome 1 following heterologous E. maxima W challenge in the intercross population. This mapped several megabases away from the quantitative trait locus (QTL) linked to the backcross primary W strain infection, suggesting different underlying mechanisms for the primary- and heterologous secondary- responses. Underlying pathways for those genes located in the respective QTL for resistance to primary infection and protection againstheterologous challenge were related mainly to immune response, with IL-10 signalling in the backcross primary challenge being the most significant. Additionally, the identified markers associated with IL-10 levels exhibited significant additive genetic variance. We suggest this is a phenotype of interest to the outcome of challenge, being scalable in live birds and negating the requirement for single-bird cages, faecal oocyst counts, or slaughter for sampling (qPCR).

Sheep naturally acquire a degree of resistant immunity to parasitic worm infection through repeated exposure. However, the immune response and clinical outcome vary greatly between animals. Genetic polymorphisms in genes integral to differential T helper cell polarization may contribute to variation in host response and disease outcome. A total of twelve single nucleotide polymorphisms (SNPs) were sequenced in IL23R, RORC2 and TBX21 from genomic DNA of Scottish Blackface lambs. Of the twelve SNPs, six were non-synonymous (missense), four were within the 3’ UTRs and two were intronic. The association between nine of these SNPs and the traits of body weight, faecal egg count (FEC) and relative T. circumcincta L3-specific IgA antibody levels was assessed in a population of domestic Scottish Blackface ewe lambs and a population of free-living Soay ewe lambs both naturally infected with a mixture of nematodes. There were no significant associations identified between any of the SNPs and phenotypes recorded in either of the populations after adjustment for multiple testing (Bonferroni corrected P value ≤ 0.002). In the Blackface lambs, there was a nominally significant association (P = 0.007) between IL23R p.V324M and weight at 20 weeks. This association may be worthy of further investigation in a larger sample of sheep.

In goats, classical genetic studies reported a large number of alleles at the Agouti locus with effects on coat color and pattern distribution. From these early studies, the dominant A(Wt) (white/tan) allele was suggested to cause the white color of the Saanen breed. Here, we sequenced the coding region of the goat ASIP gene in 6 goat breeds (Girgentana, Maltese, Derivata di Siria, Murciano-Granadina, Camosciata delle Alpi, and Saanen), with different coat colors and patterns. Five single nucleotide polymorphisms (SNPs) were identified, 3 of which caused missense mutations in conserved positions of the cysteine-rich carboxy-terminal domain of the protein (p.Ala96Gly, p.Cys126Gly, and p.Val128Gly). Allele and genotype frequencies suggested that these mutations are not associated or not completely associated with coat color in the investigated goat breeds. Moreover, genotyping and sequencing results, deviation from Hardy-Weinberg equilibrium, as well as allele copy number evaluation from semiquantitative fluorescent multiplex PCR, indicated the presence of copy number variation (CNV) in all investigated breeds. To confirm the presence of CNV and evaluate its extension, we applied a bovine-goat cross-species array comparative genome hybridization (aCGH) experiment using a custom tiling array based on bovine chromosome 13. aCGH results obtained for 8 goat DNA samples confirmed the presence of CNV affecting a region of less that 100 kb including the ASIP and AHCY genes. In Girgentana and Saanen breeds, this CNV might cause the A(Wt) allele, as already suggested for a similar structural mutation in sheep affecting the ASIP and AHCY genes, providing evidence for a recurrent interspecies CNV. However, other mechanisms may also be involved in determining coat color in these 2 breeds.

Background Somatic cell score (SCS) has been promoted as a selection criterion to improve mastitis resistance. However, SCS from healthy and infected animals may be considered as separate traits. Moreover, imperfect sensitivity and specificity could influence animals' classification and impact on estimated variance components. This study was aimed at: (1) estimating the heritability of bacteria negative SCS, bacteria positive SCS, and infection status, (2) estimating phenotypic and genetic correlations between bacteria negative and bacteria positive SCS, and the genetic correlation between bacteria negative SCS and infection status, and (3) evaluating the impact of imperfect diagnosis of infection on variance component estimates. Methods Data on SCS and udder infection status for 1,120 ewes were collected from four Valle del Belice flocks. The pedigree file included 1,603 animals. The SCS dataset was split according to whether animals were infected or not at the time of sampling. A repeatability test-day animal model was used to estimate genetic parameters for SCS traits and the heritability of infection status. The genetic correlation between bacteria negative SCS and infection status was estimated using an MCMC threshold model, implemented by Gibbs Sampling. Results The heritability was 0.10 for bacteria negative SCS, 0.03 for bacteria positive SCS, and 0.09 for infection status, on the liability scale. The genetic correlation between bacteria negative and bacteria positive SCS was 0.62, suggesting that they may be genetically different traits. The genetic correlation between bacteria negative SCS and infection status was 0.51. We demonstrate that imperfect diagnosis of infection leads to underestimation of differences between bacteria negative and bacteria positive SCS, and we derive formulae to predict impacts on estimated genetic parameters. Conclusions The results suggest that bacteria negative and bacteria positive SCS are genetically different traits. A positive genetic correlation between bacteria negative SCS and liability to infection was found, suggesting that the approach of selecting animals for decreased SCS should help to reduce mastitis prevalence. However, the results show that imperfect diagnosis of infection has an impact on estimated genetic parameters, which may reduce the efficiency of selection strategies aiming at distinguishing between bacteria negative and bacteria positive SCS.

Nowadays in dairy sheep, test-day records are collected monthly under an alternate morning/evening system. This alternate system was implemented because of the steady increase in recording cost per sheep observed in the last few decades. Furthermore, additional modifications to the testing schemes have been proposed to reduce the costs of milk recording. In dairy sheep, the cost for milk recording is indeed too high compared both with individual outputs and with other dairy species. Therefore, the purposes of the present study were: i) to compare estimated breeding values (EBVs) for milk yield using different simplified testing schemes with a test-day sire model; ii) to evaluate the effect of different testing schemes on the ranking of top rams; and iii) to evaluate the effect of different testing schemes on the genetic progress, based on sire selection. A total of 28,304 test-day records from 4,968 lactations of 2,429 Valle del Belice ewes, collected in 15 flocks between 1994 and 2006, were used for the analysis. To have the same ewes through different testing schemes, it was requested that a ewe have at least six test-day records included in the dataset. The pedigree file included a total of 206 sires. The response variable was the daily milk production. Four different recording schemes were used to estimate breeding values and to make comparisons. The reference scheme considered all data obtained from ewes in the present recording system in which ewes in lactation were tested every month. Three alternative schemes that used less information were considered. A random regression sire model that used a Legendre function of days in milk was fitted. EBVs obtained with alternative recording schemes and under different intensities of selection showed different degrees of Spearman correlation with EBVs obtained using the monthly recording scheme. These correlations ranged from 0.68 to 0.98. The consequence of moving the test-day schedule to one of these schemes will produce a decrease in genetic response to selection due to the associated loss of intensity and accuracy. Consequently, before given any recommendation in this regard, further research should be done to better elucidate the consequences of a change in the scheme of test-day collection.

Intramammary infections (IMI) are a complex of inflammatory diseases of the mammary gland. Mastitis is one of the most frequent IMI affecting small dairy ruminants. Direct selection against clinical mastitis is difficult because mastitis in not widely recorded; therefore, somatic cell count (SCC) is promoted as selection criterion for mastitis resistance. A dataset containing 2,457 first- lactation Valle del Belice ewes from 14 flocks recorded from 1998 to 2003 was analysed. In total 116 sires with at least four daughters with a record were included in the pedigree file. Test-day IMI events were coded as a binary trait using a SCC cut-off value of 750,000 cells/ml. Analyses of risk factors for the binary IMI trait were based on a logistic regression model. The herd effect was the major risk factor for IMI. The risk of culling due to IMI increased for late season of lambing. A single trait threshold sire model was applied. The heritability calculated using a logit function was 0.16±0.072 very close to the expected value of 0.14 calculated with Dempster and Lerner’s formula treating IMI as a continuous variable.

Mastitis is an inflammation of the udder, which leads to economic loss, mainly consisting of discarded milk, reduced milk production and quality, and increased health costs. Somatic cell count (SCC), and therefore somatic cell score (SCS), is widely used as indicator of mastitis. In this thesis, I focus on the genetic parameters of SCS as indicator of mastitis, and on the possibilities of using this trait for selection for mastitis resistance in the Valle del Belice dairy sheep. In Chapter 1, mastitis and SCS are defined and introduced. Chapter 2 deals with the estimation of genetic parameters for SCS and milk production traits in primiparous Valle del Belice ewes. Heritability estimates ranged from 0.09 to 0.14 for milk, fat and protein yields and contents. For SCS, the heritability of 0.14 was relatively high. SCS was genetically positively correlated to milk, fat and protein yields and contents. However, correlations were not extreme, so simultaneous improvement for milk yield and SCS seems possible. In Chapter 3, the level of SCC is included in a survival analysis to evaluate the effect of SCC on functional longevity. Results showed that an increase in SCC was associated with an increase in culling rate.Elevated SCC, therefore, play an indirect role in the culling decisions of Valle del Belice dairy sheep farmers, although, at present, farmers do not directly select for reduced SCC. In Chapter 4, the genetic parameters of the infection status and SCS, according to whether the samples were bacteria negative or positive are reported. Moreover, the impact of imperfect sensitivity and specificity on variance component estimates was investigated. The heritability was 0.10 for bacteria negative SCS, 0.03 for bacteria positive SCS, and 0.09 for infection status, on the liability scale. The genetic correlation between bacteria negative and bacteria positive SCS (0.62) suggests that they may be genetically different traits, confirming that SCSfrom healthy and infected animals should be analyzed separately. Moreover, a positive genetic correlation between bacteria negative SCS and liability to mastitis was found, suggesting that the approach of selecting animals for decreased SCS will help to reduce the prevalence of mastitis. The results also showed that the imperfect diagnosis of infection has an impact on estimated genetic parameters,which may reduce the efficiency of selection strategies aiming at distinguishing between bacteria negative and bacteria positive SCS. In Chapter 5, the diagnostic ability of SCCand California Mastitis Test (CMT) to detect intramammary infectionswas evaluated by using the Receiver-Operating Characteristic(ROC) curves, in order to identify a SCCthreshold that better discriminated healthy from infected udders. The results indicate that the CMT can only discriminate the udders infected from major pathogens. Nevertheless, in general SCS was the best indirect test for the bacteriological status of the udder. The final chapter explores and discusses the opportunities to use SCS as indicator of mastitis in a selection scheme to improve mastitis resistance for the Valle del Belice dairy sheep breed.

BACKGROUND: Somatic cell score (SCS) has been promoted as a selection criterion to improve mastitis resistance. However, SCS from healthy and infected animals may be considered as separate traits. Moreover, imperfect sensitivity and specificity could influence animals' classification and impact on estimated variance components. This study was aimed at: (1) estimating the heritability of bacteria negative SCS, bacteria positive SCS, and infection status, (2) estimating phenotypic and genetic correlations between bacteria negative and bacteria positive SCS, and the genetic correlation between bacteria negative SCS and infection status, and (3) evaluating the impact of imperfect diagnosis of infection on variance component estimates. METHODS: Data on SCS and udder infection status for 1,120 ewes were collected from four Valle del Belice flocks. The pedigree file included 1,603 animals. The SCS dataset was split according to whether animals were infected or not at the time of sampling. A repeatability test-day animal model was used to estimate genetic parameters for SCS traits and the heritability of infection status. The genetic correlation between bacteria negative SCS and infection status was estimated using an MCMC threshold model, implemented by Gibbs Sampling. RESULTS: The heritability was 0.10 for bacteria negative SCS, 0.03 for bacteria positive SCS, and 0.09 for infection status, on the liability scale. The genetic correlation between bacteria negative and bacteria positive SCS was 0.62, suggesting that they may be genetically different traits. The genetic correlation between bacteria negative SCS and infection status was 0.51. We demonstrate that imperfect diagnosis of infection leads to underestimation of differences between bacteria negative and bacteria positive SCS, and we derive formulae to predict impacts on estimated genetic parameters. CONCLUSIONS: The results suggest that bacteria negative and bacteria positive SCS are genetically different traits. A positive genetic correlation between bacteria negative SCS and liability to infection was found, suggesting that the approach of selecting animals for decreased SCS should help to reduce mastitis prevalence. However, the results show that imperfect diagnosis of infection has an impact on estimated genetic parameters, which may reduce the efficiency of selection strategies aiming at distinguishing between bacteria negative and bacteria positive SCS