Basal-like breast cancers form a distinct subtype of breast cancer characterized by the expression of markers expressed in normal basal/myoepithelial cells. Breast cancers arising in carriers of germline BRCA1 mutations are predominately of basal-like type, suggesting that BRCA1 dysfunction may play a role in the pathogenesis of sporadic basal-like cancers. We analysed 37 sporadic breast cancers expressing the basal marker cytokeratin 5/6, and age-and grade-matched controls, for downregulation of BRCA1. Although BRCA1 promoter methylation was no more common in basal-like cancers (basal 14% vs controls 11%, P ¼ 0.72), BRCA1 messenger RNA expression was twofold lower in basal-like breast cancers compared to matched controls (P ¼ 0.008). ID4, a negative regulator of BRCA1, was expressed at 9.1-fold higher levels in basal-like breast cancer (Po0.0001), suggesting a potential mechanism of BRCA1 downregulation. BRCA1 downregulation correlated with the presence of multiple basal markers, revealing heterogeneity in the basal-like phenotype. Finally, we found that 63% of metaplastic breast cancers, a rare type of basal-like cancers, had BRCA1 methylation, in comparison to 12% of controls (Po0.0001). The high prevalence of BRCA1 dysfunction identified in this study could be exploited in the development of novel approaches to targeted treatment of basal-like breast cancer.

During 1977 a survey was undertaken by practising veterinary surgeons of the incidence of different lesions causing lameness in dairy cattle. Forty-eight veterinary practices participated and they treated 7526 cases of lameness in 1821 herds. The average incidence of lameness among all cows was 5.5 per cent and the annual incidence among practices ranged from 1.8 to 11.8 per cent. Most lesions (88.3 per cent) occurred in the feet; the commonest were foul of the foot (16.7 per cent), white line abscess (15.6 per cent), sole ulcer (13.6 per cent), punctured sole and pus (10.4 per cent) and underrun heel (8.7 per cent). These proportions varied in different parts of the country. Eighty-four per cent of foot lesions occurred in the hind feet and of these lesions 85 per cent occurred in the outer claw; 42 per cent of foot lesions occurred in abnormally shaped claws. The remaining 11.7 per cent of lesions occurred in the legs and trunk, 76 per cent of which occurred in the hindlimb. Trauma was the main cause of leg lesions, which occurred most frequently in the joints and ligaments.

One thousand, four hundred and ninety-one lactations in 770 Friesian, Holstein and Ayrshire crossbred cows have been used to study the associations between lameness and fertility. Lameness was associated with a longer interval between calving and first service and a longer interval between calving and conception. The largest increases in these intervals, of 17 and 30 days, respectively, occurred in cows with either sole or white line lesions occurring between 36 and 70 days after calving. The conception rate during the 63 days before a diagnosis of lameness was made was lower (31 per cent) than at other times (40 per cent).

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Lameness in herds during one year was commonest in the first month of lactation (15 per cent of all cases). Leg lesions were particularly common at this time (24 per cent of all cases of leg lesions) but white line abscess and sole ulcer were more common a month later. Foul-in-the-foot was one of the two most common lesions at all stages of pregnancy and lactation, and white line abscess the most common (20 per cent of all lesions) in late lactation. Both sole ulcer and underrun heel had lower incidence in the second half of the year than the first. White line abscess was particularly common in March and November although there were significant interactions between month and veterinary practice; foul-in-the-foot was most common in October. Susceptibility to lameness increased with age; 10-year-old cows were over four times more likely to develop lameness than three-year-old cows. This was due particularly to increased incidence with age of white line abscess and sole ulcer and, to a lesser extent, underrun heel. In contrast, foul-in-the-foot and leg lesions showed little change with age. Whereas these lesions accounted for 68 per cent of the total in cows up to two years old, they accounted for only 15 per cent of all lesions in cows over 10 years old. White line abscess was slightly commoner in cows with large heart girths.

BackgroundAcute exacerbations and disease progression in interstitial lung disease (AE-ILD) pose important challenges to clinicians and patients. AE-ILD are variable in presentation but may result in rapid progression of ILD, respiratory failure and death. However, in many cases AE-ILD may go unrecognised so that their true impact and response to therapy is unknown. The potential for home monitoring to facilitate early, and accurate, identification of AE and/or ILD progression has gained interest. With increasing evidence available, there is a need for a systematic review on home monitoring of patients with ILD to summarise the existing data.AimTo systematically evaluate the evidence for use of home monitoring for early detection of exacerbations and/or progression of ILD.MethodWe searched Ovid-EMBASE, MEDLINE, and CINAHL using MeSH terms in accordance with the PRISMA guidelines. PROSPERO registration number (CRD42020215166).ResultsThirteen studies comprising 968 patients have demonstrated that home monitoring is feasible and of potential benefit in patients with ILD. Nine studies reported that mean adherence to home monitoring was greater than 75%, and where spirometry was performed there was a significant correlation (r=0.72–0.98, p<0.001) between home and hospital-based readings. Two studies suggested that home monitoring of Forced Vital Capacity (FVC) might facilitate detection of progression in idiopathic pulmonary fibrosis (IPF).ConclusionDespite the fact that individual studies in this systematic review provide supportive evidence suggesting the feasibility and utility of home monitoring in ILD, further studies are necessary to quantify the potential of home monitoring to detect disease progression and/or acute exacerbations.

The incidence of lameness in herds visited by veterinary practitioners in winter (0.87 cases per 100 cows per month) was greater than in summer (0.71 cases per 100 cows per month). The relative proportions of leg lesions and underrun heel were higher, and those of foul-in-the-foot, interdigital hyperplasia and foreign body in the sole were lower in winter than in summer. In winter, leg lesions and aseptic laminitis were most common in cows housed in cowsheds, white line abscess in cows in strawyards and sole ulcer in cows in either cowsheds or cubicles with concrete yards. The overall incidence of lesions was lower in strawyard accommodation (0.71 cases per 100 cows per month) than in cubicles with yards (0.93 cases per 100 cows per month). Veterinary practitioners saw proportionally fewer cases of foul-in-the-foot but proportionally more cases of sole ulcer in larger than in smaller herds. The animal incidence of lameness ranged from 1.7 to 11.4 per cent among practices; in 20 practices which recorded a total of at least 100 lesions in both summer and winter there was a large variation in the proportions observed of each lesion. A principal component analysis contrasted those practices which tended to see mainly cases of white line abscess, white line separation, foul-in-the-foot and leg lesions with those which saw mainly cases of underrun heel, interdigital hyperplasia, punctured sole with pus and sole ulcer. Twenty-nine per cent of cases of underrun heel and 22 per cent of cases of both deep sepsis and interdigital hyperplasia occurred in conjunction with another lesion.

Diets of different protein content were fed to dairy cows in two experiments of seven months and 12 months duration. Significant differences in the mean concentrations of serum urea, albumin and copper and of blood haemoglobin and packed cell volume were observed between cows receiving the various diets. The greatest differences occurred when cows were in mid-lactation. It was concluded that concentrations of urea in the serum of the cows were reflecting dietary protein intake and that concentrations of albumin, haemoglobin and PCV during lactation were affected by long-term protein status. The possible significance of the results is discussed in relation to previous reports indicating interrelationships between protein and copper metabolism, and in relation to the recommended protein content of diets for cows.