Towards genomic selection for facial eczema disease tolerance in the New Zealand sheep industry.

Pithomycotoxicosis, more commonly known as facial eczema (FE), is a liver disease that occurs predominantly in New Zealand because of its toxigenic Pithomyces chartarum strains. The first reported case was in sheep in 1887. Since the 1930s, a number of studies have been conducted in an attempt to mitigate the problems FE has on the sheep and dairy industries. The research in these studies included work on fungicide and biological control of the saprophytic fungus, use of different pasture plants to inhibit fungal growth, stock management with respect to pasture fungal spore counts and the use of zinc prophylaxis on animals. The finding that there was a genetic basis in FE sensitivity in sheep prompted research for a genetic approach to mitigation in the form of a diagnostic DNA test for susceptibility to the disease. Recently, we have used the Illumina OvineSNP50 BeadChip to develop a genome-enabled prediction approach to screen for FE-tolerant sheep. Our current best genomic prediction for FE is for the Romney breed and has an accuracy of 0.38. This prediction accuracy is not as high as the individual accuracy gained by an artificial challenge test (0.64). However, it has the advantage of being a non-invasive test and can be provided as part of genomic testing for other traits at minimal cost.

Identifying chromosomal selection-sweep regions in facial eczema selection-line animals using an ovine 50K-SNP array.

Facial eczema (FE) is a hepato-mycotoxicosis found mainly in New Zealand sheep and cattle. When genetics was found to be a factor in FE susceptibility, resistant and susceptible selection lines of Romney sheep were established to enable further investigations of this disease trait. Using the Illumina OvineSNP50 BeadChip, we conducted a selection-sweep experiment on these FE genetic lines. Two analytical methods were used to detect selection signals, namely the Peddrift test (Dodds & McEwan, 1997) and fixation index FST (Weir & Hill, 2002). Of 50 975 single nucleotide polymorphism (SNP) markers tested, there were three that showed highly significant allele frequency differences between the resistant and susceptible animals (Peddrift nominal P < 0.000001). These SNP loci are located on chromosomes OAR1, OAR11 and OAR12 that coincide precisely with the three highest genomic FST peaks. In addition, there are nine less significant Peddrift SNPs (nominal P ≤ 0.000009) on OAR6 (n = 2), OAR9 (n = 2), OAR12, OAR19 (n = 2), OAR24 and OAR26. In smoothed FST (five-SNP moving average) plots, the five most prominent peaks are on OAR1, OAR6, OAR7, OAR13 and OAR19. Although these smoothed FST peaks do not coincide with the three most significant Peddrift SNP loci, two (on OAR6 and OAR19) overlap with the set of less significant Peddrift SNPs above. Of these 12 Peddrift SNPs and five smoothed FST regions, none is close to the FE candidate genes catalase and ABCG2; however, two on OAR1 and one on OAR13 fall within suggestive quantitative trait locus regions identified in a previous genome screen experiment. The present studies indicated that there are at least eight genomic regions that underwent a selection sweep in the FE lines.

Varying ratios of omega-6: omega-3 fatty acids on the pre-and postmortem bone mineral density, bone ash, and bone breaking strength of laying chickens.

The purpose of this study was to investigate the effects of varying ratios of n-6 to n-3 fatty acids in the diets of White Leghorn chickens on tibia bone characteristics [bone mineral density, bone mineral content (BMC), ash bone mineral content, bone morphology, and cortical thickness] and tibia bone strength parameters (ultimate force, bending stress, maximum strain, Young's modulus of elasticity, area under the curve, and moment of inertia). Seventy-five 16-wk-old female White Leghorn chickens were randomly assigned to 1 of 5 dietary ratios of n-6 to n-3 fatty acids: 47.8:1, 18.0:1, 7.6:1, 5.9:1, or 4.7:1. Corn oil was the n-6 fatty acid source, whereas flax oil provided the n-3 fatty acids. Bone density was measured on the left tibia via dual-energy x-ray absorptiometry (DXA) prior to killing and after excision. Bones were ashed in a muffle furnace at 500 degrees F. Tibia bones were broken by using a 3-point bending rig. Results showed no significant effect of diet on bone characteristics. There were no significant differences among diet groups for parameters of bone strength except cortical thickness (P < or = 0.01). Bone mineral content determined by ashing was significantly different by 9.2% (P < or = 0.0001) from BMC determined in vivo by DXA; however, there were no differences in ex vivo BMC and BMC ash, although they were highly correlated (r = 0.99, P < or = 0.0001). We concluded that there was no effect of n-3 fatty acids on tibia bone in mature White Leghorn chickens. The GE Lunar Prodigy DXA instrument significantly underestimated the in vivo BMC in chickens.

Solaria compliance in an unregulated environment: the Australian experience.

This study aimed to explore compliance with international recommendations on solaria use in a unregulated setting. Simulated customers visited 176 solaria operating in Australia and two face-to-face visits and one telephone contact were made for each establishment. From the survey, establishments compliant with the recommendations ranged from: 1.1% refusing access to the customer with skin type I; 9.7% recommending to the customer with skin type I against solaria use and up to 87.5% assessing skin type and recommending eye protection. Few (15.9%) were compliant with more than 10 of the 13 recommendations. Establishment type and number of sunbeds were significantly associated with compliance. This study has shown that a much higher level of compliance with recommendations, particularly those excluding higher-risk groups, is required to reduce the harm associated with use of solaria. While new legislation may be useful, other harm minimisation strategies including mandatory staff training and taxation should be considered.

Pre-diabetic blood pressure predicts urinary albumin excretion after the onset of type 2 (non-insulin-dependent) diabetes mellitus in Pima Indians.

Blood pressure was measured in 490 non-proteinuric Pima Indians from the Gila River Indian Community in Arizona at least 1 year before the diagnosis of Type 2 (non-insulin-dependent) diabetes mellitus. Urine albumin concentration was measured in the same subjects 0-24 years (mean 5 years) after diabetes was diagnosed. Prevalence rates of abnormal albumin excretion (albumin-to-creatinine ratio > or = 100 mg/g) after the onset of Type 2 diabetes were 9%, 16%, and 23%, respectively, for the lowest to highest tertiles of pre-diabetic mean blood pressure. When controlled for age, sex, duration of diabetes and pre-diabetic 2-h post-load plasma glucose concentration, higher pre-diabetic mean blood pressure predicted abnormal urinary excretion of albumin after the onset of diabetes. This finding suggests that the higher blood pressure seen in diabetic nephropathy is not entirely a result of the renal disease, but may precede and contribute to it.

Definition of glomerular antigens by monoclonal antibodies produced against a human glomerular membrane fraction.

Experimental animal models of glomerulonephritis (GN) produced by direct antibody binding to non-basement membrane glomerular capillary wall antigens do not to date have human parallels. To examine the potential for this form of humoral glomerular injury in man, we sought to define discrete human non-GBM glomerular antigenic targets using hybridoma technology. Mice were immunised intraperitoneally with 20-100 micrograms of a human glomerular membrane fraction (HGMF). Six fusions have yielded 12 stable reagents defined by positive glomerular indirect immunofluorescence (IF) and microELISA using HGMF as the screening antigen. Subclass analysis of ascitic McAbs indicated several IgG1, one IgG2b, and three IgM reagents. Distinctive IF patterns of reactivity with epithelial, endothelial or mesangial structures have been observed, with or without peritubular capillary, tubular basement membrane and vessel wall reactivity. Seven normal non-renal human organs and the kidneys of rat, rabbit and sheep have shown patterns characteristic of each individual McAb, restricted to human or with species cross reactivity. To partially characterise McAb-reactive antigens, detergent-solubilised renal cortex and collagenase-solubilised GBM (CS-GBM) extracts have been probed by immunoblot. A unique McAb 7-5Q, reactive with glomerular and tubular epithelial structures, binds major bands of approximately 107 KD and 93 KD in detergent solubilised cortex and a single band of similar size by immunoprecipitation (110 KD). 5-3A (a human-restricted linear-reacting McAb) binds bands of 20-200 KD (major band 58 KD) in CS-GBM. In conclusion, distinct species-restricted and more broadly disposed glomerular epitopes are definable in man by McAbs and are potential targets for humoral injury. Purification of these antigens will allow assay for circulating putative nephritogenic auto-antibody and potentially, McAbs may be useful in screening urine for evidence of occult structural renal disease.

Effect of proteinuria on mortality in NIDDM.

The effect of proteinuria (greater than or equal to approximately 1 g/day) on mortality in non-insulin-dependent diabetes mellitus (NIDDM) was assessed in Pima Indians aged greater than or equal to 45 yr. Among 1426 subjects, 48% with NIDDM at the beginning of followup, there were 489 deaths in 13,345 person-yr of observation. The age- and sex-adjusted mortality rate was 32.7/1000 person-yr (95% Cl = 27.6, 37.8) in diabetic subjects without proteinuria, similar to the rate of 30.1/1000 person-yr (95% Cl = 25.7, 34.4) in nondiabetic subjects without proteinuria. By contrast, in diabetic subjects with proteinuria the mortality rate was 121.4/1000 person-yr (95% Cl = 97.5, 145.3). When controlled for age, sex, and diabetes duration, diabetic subjects with proteinuria had a death rate 3.5 times as high (95% Cl = 2.8, 4.4) as those without proteinuria. Of the excess mortality associated with NIDDM in Pima Indians, 97% was found in subjects with proteinuria. The death rate in diabetic subjects without proteinuria was not appreciably greater than the rate in nondiabetic subjects. Mortality rates from uremia and cardiovascular disease were significantly higher in diabetic Pima Indians with proteinuria than in those without. These relationships are similar to observations reported in people with insulin-dependent diabetes.

Congenital susceptibility to NIDDM. Role of intrauterine environment.

Non-insulin-dependent diabetes mellitus (NIDDM) during pregnancy in Pima Indian women results in offspring who have a higher prevalence of NIDDM (45%) at age 20-24 yr than in offspring of nondiabetic women (1.4%) or offspring of prediabetic women (8.6%), i.e., women who developed diabetes only after the pregnancy. These differences persist after taking into account paternal diabetes, age at onset of diabetes in the parents, and the offspring's weight relative to height. The findings suggest that the intrauterine environment is an important determinant of the development of diabetes and that its effect is in addition to effects of genetic factors.

Obesity in offspring of diabetic Pima Indian women despite normal birth weight.

The relationships of birth weight and maternal diabetes to the development of obesity were examined at 5-19 yr of age in the offspring of Pima Indian women. At each age, offspring of diabetic women, even those who were of normal birth weight, had a higher mean weight relative to height than offspring of nondiabetic and prediabetic women. Birth weight was predictive of relative weight in 5- to 9- and 10- to 14-yr-old offspring of nondiabetic women but not in the oldest group. In contrast, for offspring of prediabetic and diabetic women, birth weight was not predictive of subsequent obesity at any age studied. Offspring of diabetic women were heavier than offspring of nondiabetic and prediabetic women regardless of birth weight. Thus, maternal diabetes was important in predicting body size in the offspring even after accounting for the effects of the birth weight and maternal body size.

On the recognition of printed characters of any font and size.

We describe the current state of a system that recognizes printed text of various fonts and sizes for the Roman alphabet. The system combines several techniques in order to improve the overall recognition rate. Thinning and shape extraction are performed directly on a graph of the run-length encoding of a binary image. The resulting strokes and other shapes are mapped, using a shape-clustering approach, into binary features which are then fed into a statistical Bayesian classifier. Large-scale trials have shown better than 97 percent top choice correct performance on mixtures of six dissimilar fonts, and over 99 percent on most single fonts, over a range of point sizes. Certain remaining confusion classes are disambiguated through contour analysis, and characters suspected of being merged are broken and reclassified. Finally, layout and linguistic context are applied. The results are illustrated by sample pages.

Immediate coronary care in general practice--a three-year review.

The general practitioners in a rural practice in a three-year period were called to 101 patients (25% female) who suffered a myocardial infarction. The average response time was 15 minutes. Seventeen patients collapsed and died and the 84 who survived the initial period were given immediate coronary care and either cared for at home, admitted by cardiac ambulance to a coronary care unit, or admitted to a general medical ward with monitor facilities. The four-week mortality rates were 21.0%, 21.5% and 57.7% respectively. Thirty-six patients required treatment for arrhythmias in the initial care period, of whom nine required defibrillation. This survey supports the view that patients over the age of 60 years with uncomplicated myocardial infarction may be cared for successfully at home.

Gestational diabetes mellitus and impaired glucose tolerance during pregnancy. Long-term effects on obesity and glucose tolerance in the offspring.

The effects of disturbances in carbohydrate metabolism during gestation were studied in the offspring of 1049 Pima Indian women who had no previous diagnosis of diabetes. Rates of fetal and maternal complications of pregnancy among women with diabetes first diagnosed during the pregnancy were similar to those among women in whom diabetes was recognized before gestation. Offspring, aged 5-19 yr, of women with abnormal glucose tolerance during pregnancy had a higher mean percent desirable weight and a higher mean postchallenge plasma glucose concentration than did offspring of women with normal glucose tolerance. Percent desirable weight and glucose concentration, however, were both lower than found in offspring of women with diabetes diagnosed before the pregnancy. Thus, metabolic events during pregnancy, as indicated by the detection of abnormal glucose tolerance during gestation, appear to have long-term effects on obesity and glucose tolerance in the offspring.

Sustained reduction of proteinuria in type 2 (non-insulin-dependent) diabetes following diet-induced reduction of hyperglycaemia.

To determine whether sustained control of hyperglycaemia in Type 2 (non-insulin-dependent) diabetic patients would diminish proteinuria, the effect of hypocaloric diet therapy (500 kcal/day) on proteinuria was assessed in obese, Type 2 diabetic patients (n = 24) and compared with results obtained for obese subjects with normal glucose tolerance (n = 7) and impaired glucose tolerance (n = 6). Diet therapy of similar mean duration resulted in similar percentage weight loss (mean percentage of original weight +/- SEM) in diabetic (13.6 +/- 1.6%), glucose intolerant (16.4 +/- 3.3%) and obese non-diabetic (11.0 +/- 1.0%) subjects. Following therapy, plasma glucose concentrations 2h after an oral glucose load declined in the diabetic (18.34 +/- 0.81 to 10.67 +/- 0.50 mmol/l, mean +/- SEM; p less than 0.001) and in the glucose intolerant subjects (10.2 +/- 0.3 to 7.3 +/- 0.4 mmol/l, p less than 0.01) while remaining unchanged in the obese non-diabetic subjects (7.09 +/- 0.23 to 6.77 +/- 0.32 mmol/l, NS). Concentrations of total protein of plasma origin and albumin in 24-h urine collections were quantified by a sensitive immunonephelometric assay using specific antisera. Initially, 24-h excretion of total protein and albumin were elevated in the diabetic [mg protein/24 h; (median +/- 95% confidence limits): 63 (42-138), p less than 0.05; albumin: 26 (14-56), p less than 0.05] and glucose intolerant subjects [protein: 52 (13-92), NS; albumin: 24 (3-61), NS] compared with the non-diabetic subjects [protein: 20 (5-38); albumin: 6.2 (3.5-9.5)].(ABSTRACT TRUNCATED AT 250 WORDS)

Excessive obesity in offspring of Pima Indian women with diabetes during pregnancy.

We studied the relation in Pima Indians between obesity in children and diabetes during pregnancy in their mothers. Sixty-eight children of 49 women who had had diabetes during pregnancy had a higher prevalence of obesity than 541 children of 134 women who subsequently had diabetes (prediabetics) or than 1326 children of 446 women who remained nondiabetic. At 15 to 19 years of age, 58 per cent of the offspring of diabetics weighed 140 per cent or more of their desirable weight, as compared with 17 per cent of the offspring of nondiabetics and 25 per cent of those of prediabetics (P less than 0.001). Obesity in the offspring was directly related to maternal diabetes, since the association was not substantially confounded by maternal obesity. The findings strongly suggest that the prenatal environment of the offspring of diabetic women results in the development of obesity in childhood and early adulthood.

Intestinal pseudo-obstruction as the presenting manifestation of small-cell carcinoma of the lung. A paraneoplastic neuropathy of the gastrointestinal tract.

A 58-year-old woman who had presented with intestinal pseudo-obstruction died 9 months later from rapidly progressive neurologic symptoms and autonomic insufficiency. Her gastric emptying had been markedly delayed and transit of markers had been slowed throughout the small bowel. A 5-hour manometric recording of the antrum and duodenum had shown absence of the normal interdigestive motor complex, which was replaced by irregular contractile activity of reduced amplitude. A small-cell carcinoma of the lung was found at autopsy. Pathologic study of the gut showed widespread degeneration of the myenteric plexus, which was infiltrated by plasma cells and lymphocytes and contained significantly reduced numbers of neurons. The extra-intestinal nervous system had neuronal loss and lymphocytic infiltrates in dorsal root ganglia. Thus, a gastrointestinal neuropathy causing intestinal pseudo-obstruction may be the presenting manifestation of a paraneoplastic syndrome associated with small-cell carcinoma.

Normative values for brain stem auditory evoked potentials obtained by digital filtering and automatic peak detection.

A BAEP test which uses constant, high level click stimulation was developed for preliminary screening of patients with known or suspected problems in auditory information processing. Digital filtering and automatic peak detection were employed to aid in the analysis of BAEP component latencies. The results of 148 BAEP tests allowed us to select a set of normative measures: absolute peak latency, interpeak latency and left-right peak latency difference. The set of threshold values was developed for selected BAEP measures, in order to evaluate test results.