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A clinical trial employing an immunotherapeutic approach based on the use of a Toll-like receptor 3 (TLR3) agonist and tumour-derived exosomes carrying tumour-associated antigens is planned in advanced ovarian cancer in conjunction with conventional first line chemotherapy. Most patients with ovarian cancer present with advanced disease and despite high initial response rate to chemotherapy the majority will relapse within 2 years with poor overall survival. Tumour antigen-specific T cells are naturally occurring in ovarian cancer patients and T cell infiltration of the tumour is highly prognostic. Novel immunotherapy to expand and activate tumour antigen-specific T cells combined with adjuvant treatment to overcome tumour-induced immunosuppression is considered to be therapeutically beneficial. The rationale for adopting such a combined approach is discussed here.

Although breed substitution is a very common method of rapidly altering the characteristics of a livestock population, within-breed selection for lamb carcass characters is becoming more widely used in the terminal sire breeds in Britain. Such selection schemes require accurate and applicable genetic parameters for the carcass traits of interest. This paper reports a genetic analysis of 11 traits measured on 3592 lamb carcasses using a derivative-free restricted maximum likelihood technique. Because of the trial design it was possible to estimate the genetic parameters of the traits at comparable fat cover, carcass weight and age at slaughter, using appropriate within-subclass covariates.Heritability estimates for muscle depth (0·23, s.e. 0·04), muscle width (0·32, s.e. 0·05), fat depth (0·31, s.e. 0·05), caliper fat (0·23, s.e. 0·04) and conformation (0·29, s.e. 0·05) were similar in the weight and age-corrected results. Heritabilities for fat cover (0·35, s.e. 0·05), daily carcass weight gain (0·63, s.e. 0·07), and leg conformation (0·44, s.e. 0·05) were higher with slaughter at fixed weight than at fixed age. The heritabilities of traits at comparable fat cover were similar to those at comparable age at slaughter with the exception of daily carcass weight gain, fat depth, caliper fat and leg conformation.The different measures of fat were highly correlated with each other. Conformation was moderately correlated with external fat score, carcass length and muscle depth. Muscle depth was moderately correlated with carcass length. Differences were found between genetic correlations calculated at equal weight, a common point of comparison in breeding schemes, and equal fat cover, a common end-point for slaughter lambs.

Background\ud \ud Several transcription factors have been shown to play important roles in the regulation of apoptosis at the onset of murine mammary involution. These include LIF-activated STAT3, c/ebpdelta, Ap-1 and IKK/NF-κB-mediated regulation of death receptor ligands. A study of STAT3 and STAT5 transcriptional targets in mammary epithelial cells in vitro showed that both c/ebpdelta and c-fos (a component of Ap-1) were upregulated by STAT3, suggesting a degree of interdependence between these transcription factor pathways in mediating their apoptotic effects. Interestingly, while no NF-κB or IKK genes were significantly regulated by STATs, the NF-κB cofactor gene, Bcl3, was found to be a principal transcriptional target of STAT3. This factor plays a role in altering the transcriptional capacity of specific NF-κB subunits and has previously been described as an oncogene in B-cell lymphomas. In this study we set out to establish whether Bcl3 had a role in regulating the cell fate of mammary epithelial cells either in the normal mammary gland or in mammary/breast cancer.\ud Methods\ud \ud Archived material representing a range of tumour grades and types was collected from breast cancer patients immediately after surgery (tumour tissues = 122, normal tissues = 32). The median follow-up of the patients was 120 months (range 12 to 156 months). QRT-PCR for Bcl3 was performed and this information was used to determine statistically significant correlations with the clinical data on breast pathology. MCF7, T47D and MDA-MB231 human breast cancer cell lines were subjected to Bcl3-specific siRNA knockdown and subsequently assessed for cell motility characteristics using ECIS technology. Bcl3-knockout mice were assessed histologically for alterations in apoptosis rate during the adult pregnancy cycle. Western blots, quantitative PCR and DNA binding assays were used to determine the activity of molecular markers of apoptosis in these animals. Bcl3-deficient animals were crossed with mmtv-neu (c-erbB2) mice to establish the role of Bcl3 in primary (neu-dependent) mammary tumour growth, and magnetic resonance imaging was performed on tumour-bearing animals, to establish metastasis rates in the presence/absence of Bcl3.\ud Results\ud \ud An analysis of 122 human breast cancer tissues showed that Bcl3 gene expression was suppressed in a significant proportion of invasive tumours, which correlated with poor prognosis. This also correlated with a significant decrease in Bcl3 gene expression in human breast cancer cell lines exhibiting increased motility characteristics. The effects of siRNA-mediated knockdown of Bcl3 are ongoing. In the mouse mammary gland, Bcl3 expression was restricted to epithelial cells during the first 24 hours of involution. Bcl3 deficiency resulted in a transient delay in the appearance of apoptotic bodies in the early involuting mammary gland in Bcl3-/- mice, while pSTAT3 levels were unchanged compared with equivalent timepoints in control animals. The activities of initiator/executor caspases of both intrinsic and extrinsic pathways were significantly decreased in Bcl3-/- tissues at this time, which correlated with decreases in the expression of key regulators of intrinsic/extrinsic apoptosis. Results from the ongoing magnetic resonance imaging study of tumour incidence/progression in mmtv-neu/Bcl3-/- mice will be presented.\ud Conclusion\ud \ud These observations suggest that Bcl3 promotes apoptosis in the mammary gland and provides preliminary evidence of cross-talk between STAT3 and NF-κB pathways, both of which have been implicated in breast cancer. Our current data on Bcl3 in primary breast tumours and breast cancer cell lines contrasts with other studies, to suggest that Bcl3 suppresses the metastatic progression of primary breast cancer and has a neutral role in breast cancer incidence or primary tumour growth.

Group breeding schemes were introduced into Britain in the 1970s as a means of increasing the rate of genetic improvement in sheep and providing a vehicle for breeders to cooperate and pool resources. The Lleyn Group Breeding Scheme was set up in 1978 with the aim of improving several maternal traits in a breed known for its prolificacy. Although the breed originates from North Wales members of the group were drawn from different parts of Britain. Flocks in the scheme were all recorded by MLC and sheep had the possibility of being selected using MLC's selection index, appropriately weighted for the traits of interest to group members.This analysis was designed to investigate the genetic progress made in the scheme between 1979 and 1993. Three traits were analysed; adjusted early lamb weight (LW) (at eight weeks of age), mature weight (MW) (at 18-months) and litter size (LS) in the form Number of lambs born per ewe lambing (NLBEL). These three traits were investigated in ten flocks which participated in the scheme, at varying levels, during the 14-year period 1979-1993. However, only genetic progress in the nucleus flock is reported in this paper.

A group breeding scheme was set up in 1976 by 10 Welsh Mountain breeders. The objective of the scheme was to improve lamb growth rate, mature size, mothering ability and litter size by selection in a nucleus flock. The original design of the scheme involved two control flocks. The Genetic Control flock was set up from the original base population and was used to monitor environmental changes in the nucleus flock. A Commercial Control flock comprised of a random selection of ewes mated to rams, which were purchased annually and represented the average animal available in the breed. An analysis of genetic progress in lamb growth in the first 9 years of the scheme was reported by Guy et al (1986). This paper presents genetic parameters and genetic trends for three traits recorded between 1977 and 1992.

The common point at which lambs are compared is an important aspect of selection programmes for lamb carcase composition. Terminal sire flocks in the Meat and Livestock Commission's (MLC) Sheepbreeder scheme have an estimated breeding value for lean meat production calculated on their lambs at a fixed age, 20 or 21 weeks depending on the breed. However, lambs sold for slaughter from commercial flocks are killed at a commercially acceptable fat cover. In addition, many of the estimates of genetic parameters used to estimate breeding values for carcase characteristics have been calculated at a fixed weight. Little information is available on the relationship between genetic parameters calculated at these three endpoints or the effect of selecting lambs at one endpoint in breeding programmes and using a second endpoint for the slaughter generation. These issues are investigated in this paper.

The purpose of this paper is to summarise the work of two Working Parties of the European Association of Animal Production, the first of which surveyed the recording schemes for sheep which are operated in Europe, and the second which examined the selection strategies for sheep prevailing in European countries, and surveyed current procedures for estimation of breeding values. General details of recording schemes are presented for 20 countries. Information on selection and estimation of breeding value is presented for 17 countries. More detailed information is available on request.

An evaluation was carried out over a 5-year period in 10 commercial flocks of Scottish Blackface, Scottish Half-bred and Mule ewes to examine the carcass characteristics of 10 sire breeds: Border Leicester, Dorset Down, Hampshire Down, He de France, North Country Cheviot, Oxford Down, Southdown, Suffolk, Texel and Wensleydale. An average of 43 sires was used per sire breed.The analyses involved tissue separation data for a total of 1402 lambs. Analyses were carried out separately for early and late flocks determined by the time of the year in which lambs were slaughtered. Sire breeds were compared when their progeny were slaughtered at the same carcass subcutaneous fat proportion (125 g/kg, early flocks; 116 g/kg, late flocks).Texel crosses had the highest carcass lean proportion (P < 005); their advantages over the Suffolk crosses were 19 g/kg (early flocks) and 17 g/kg (late flocks) reflecting both a higher lean:bone ratio and a higher lean:fat ratio. The Suffolk crosses had a similar carcass lean proportion to other breed crosses. Border Leicester, North Country Cheviot, Texel and Wensleydale crosses tended to have less of their total lean distributed in the higher-priced joints than the Down breed crosses. However, the differences were relatively small and not of major commercial significance: the range between sire breeds was 0-01 to 0-02 of average retail value.

Carcass evaluation data from two breed-comparison trials were used to examine the value of conformation as an indicator of carcass composition when used in addition to carcass weight and different measures of fatness. One trial involved 1478 crossbred lambs out of three ewe types by Border Leicester, Dorset Down, Ile-de-France, North Country Cheviot, Oxford Down, Southdown, Suffolk, Texel and Wensleydale sires. The other trial involved 920 crossbred lambs out of two dam types by Dorset Down, Ile-de-France, Oldenburg, Oxford Down, Suffolk and Texel sires. Each trial extended over 3 years.Conformation contributed little to the prediction of carcass lean percentage or proportion of lean in the higher-priced joints, although the additional precision was often significant at PConformation was slightly more valuable for the prediction of lean to bone ratio and m. longissimus depth. The addition of sire-breed effect to weight and fat class provided an important increase in the precision of prediction of percentage lean in carcass and lean to bone ratio. Texel progeny had higher lean to bone ratios and more lean in the carcass than progeny of other sire breeds, but they did not have sufficiently high conformation scores to clearly identify this advantage.

An evaluation was carried out over a 5-year period in 10 commercial flocks of Scottish Blackface, Scottish Half-bred and Mule ewes to evaluate 10 sire breeds: Border Leicester, Dorset Down, Hampshire Down, He de France, North Country Cheviot, Oxford Down, Southdown, Suffolk, Texel and Wensleydale. An average of 43 sires was used per sire breed.The analysis involved a total of 3360 lambs of which one-third had the left side dissected. Sire breeds were compared when their progeny were slaughtered at the same estimated carcass subcutaneous fat proportion (approx. 120 g/kg).Carcass weights were related to the adult body size of the sire breeds with a range of 4 kg between Southdown and Wensleydale crosses. Crosses by the conventional meat sire breeds tended to have higher daily carcass-weight and lean-tissue gains than those by Border Leicester and Wensleydale sires. Texel and Suffolk crosses did not differ significantly in carcass weight, daily carcass-weight gain, daily lean gain or age at slaughter (P > 0·05).Significant sire-breed × dam-breed interactions were recorded for daily carcass-weight gain and daily lean gain (P < 0·05). Dorset Down and Southdown crosses tended to grow relatively faster when from Mule dams; Texel crosses grew relatively faster when from Blackface dams.There was relatively little difference between sire breeds in visually assessed carcass conformation; all the means were within two points on a 15-point scale. Texel crosses had a higher carcass lean proportion than other crosses: their advantage over Suffolk crosses was 22 g/kg.

Exponential smoothing is frequently used for the forecasts in stock control systems. The analysis given shows that intermittent demands almost always produce inappropriate stock levels. Demand for constant quantities at fixed intervals may generate stock levels of up to double the quantity really needed. A method of overcoming these difficulties is described, using separate estimates of the size of demand, and of the demand frequency. The rules for setting the safety stock levels have also to be adjusted before consistent protection can be obtained against being out of stock.

Several points mentioned by Adelson and Norman1 in their paper "Operational Research and Decision-making" are discussed critically-the selection of the model and its implication on the decision by an individual or by a committee; the choice of objectives and the degree to which objectives can guide a decision-maker; subjective probability; the evolutionary process in management decision-making.

When setting stock levels for slow-moving items, a decision should be taken as to whether the item should be stocked at all. Formulae are developed for making this decision, and for determining the optimum stock if the item should be carried.

In 1976, ten members of the Welsh Mountain Breed Society, established Camda Cynwyd Ltd as a co-operative society. The stated aim is to breed slightly bigger Welsh Mountain ewes that lamb easily and rear heavier lambs whilst retaining the hardiness and other beneficial traits of the breed.A nucleus flock of 150 ewes was created in 1976 with the more productive ewes out of each member's MLC recorded flock. Camda hired facilities for keeping and recording the nucleus flock at the ABRO hill farm, Rhydglafes, North Wales for six years. Anticipating the disposal of the ABRO farm by the AFRC in 1984, a lease was obtained on a 340 acre hill farm at Cernioge Mawr, Pentrefoeias, and the flock transferred there during the summer and autumn of 1982. Each year, fifty high performance, mature ewes (immigrants) were introduced to the nucleus from members flocks, until 1984 when it was closed.

Meetings occupy over 30 per cent of the time of an executive and existing training in meeting behaviour was not considered to be effective. Methods used to analyse communication at meetings are described. A group of observers has been trained to assist chairmen in improving the usefulness of their meetings. Reductions of 20 per cent in the number of meetings and of 30 per cent in their duration have been achieved. Standard practices for meetings have been established. Training should be given to coherent groups in the organization rather than to individuals if changes in behaviour patterns are desired.