Pedigree verification and parentage assignment using genomic information in the Mexican Holstein population

Genealogical information is an essential tool for carrying out any genetic improvement program. The objective of this study was to determine the accuracy of pedigree information in the Mexican registered Holstein population using genomic data available in Mexico and for the US Holstein population. The study included 7,508 animals (158 sires and 7,350 cows) that were born from 2002 through 2014, registered with Holstein de México, and genotyped with single nucleotide polymorphism arrays of different densities. Parentage could not be validated for 17% of sires of cows and 12% of sires of bulls. Most (79%) of the dams of cows and the dams of bulls had no genotype available and could not be validated. A parentage test was possible for only 6,104 sires of cows, 139 sires of bulls, 1,519 dams of cows, and 33 dams of bulls. Of the animals with a parentage test, parent assignment was confirmed for 89% of sires of cows, 92% of dams of cows, 95% of sires of bulls, and 97% of dams of bulls. Parent discovery was possible for some animals without confirmed parents: 17% for sires of cows, 2.5% for dams of cows, 43% for sires of bulls, and 0% for dams of bulls. Of the 7,795 progeny tests, 777 had parent conflicts, which is an error rate of 9.97% for parental recording in the population, a rate that is similar to those recently reported for other populations. True parents for some progeny conflicts (15%) were discovered for the Mexican population, and the remaining parents were assigned as unknown. Expected effects of misidentification on rate of genetic gain could be decreased by half if genealogical errors were decreased to 5%. This study indicates that genotyping and genealogy recovery may help in increasing rates of genetic improvement in the Mexican registered Holstein population.     

PRACTICAL INCONSISTENCY MANAGEMENT FOR CRITICAL-TASKS DECISION-SUPPORT SYSTEMS

Abstract

In this paper, the problem of logical consistency in critical-tasks decision systems is addressed. It is shown how local search techniques can be used to check the (in)consistency of very large propositional knowledge bases (KBs). Using new heuristic findings. we can now implement efficient forms of diagnostic reasoning in the context of very large ICBs modeling deep models of complex devices and including patterns of default reasoning.     

The limitations and potential of AVHRR GAC data for continental scale fire studies

Global Area Coverage (GAC) data from the Advanced Very High Resolution Radiometer (AVHRR) are available on a daily basis, dating back to July 1981. The AVHRR's 3·55–3·93 μm channel is suitable for detection of terrestrial hot spots, such as bushfires. The long-term archives and global cover make the GAC a potentially valuable data source for large scale fire studies. However, these data are sampled spatially through a combination of line skipping and averaging. This study shows that the sampling affects the sensitivity of GAC for fire detection in relation to ecosystem and season. The GAC are found to provide a reasonable measure of fire activity in grassland and open b'ush savannah, but to perform poorly in the forest margins. Overall at least 79 per cent of fires detected with non-sampled AVHRR data are missed by the GAC. This severely limits the use of GAC data for quantitative fire studies. The GAC does appear to provide a reasonable measure of fire calendar (i.e., variations in fire activity with time) and on a continental scale successfully identifies the main regions of fire activity. The potential of these data for continental scale fire studies is illustrated through the preliminary analysis of 277 GAC mosaics of Africa for the period September 1988 to August 1989.     

Cow genotyping strategies for genomic selection in a small dairy cattle population

This study compares how different cow genotyping strategies increase the accuracy of genomic estimated breeding values (EBV) in dairy cattle breeds with low numbers. In these breeds, few sires have progeny records, and genotyping cows can improve the accuracy of genomic EBV. The Guernsey breed is a small dairy cattle breed with approximately 14,000 recorded individuals worldwide. Predictions of phenotypes of milk yield, fat yield, protein yield, and calving interval were made for Guernsey cows from England and Guernsey Island using genomic EBV, with training sets including 197 de-regressed proofs of genotyped bulls, with cows selected from among 1,440 genotyped cows using different genotyping strategies. Accuracies of predictions were tested using 10-fold cross-validation among the cows. Genomic EBV were predicted using 4 different methods: (1) pedigree BLUP, (2) genomic BLUP using only bulls, (3) univariate genomic BLUP using bulls and cows, and (4) bivariate genomic BLUP. Genotyping cows with phenotypes and using their data for the prediction of single nucleotide polymorphism effects increased the correlation between genomic EBV and phenotypes compared with using only bulls by 0.163 ± 0.022 for milk yield, 0.111 ± 0.021 for fat yield, and 0.113 ± 0.018 for protein yield; a decrease of 0.014 ± 0.010 for calving interval from a low base was the only exception. Genetic correlation between phenotypes from bulls and cows were approximately 0.6 for all yield traits and significantly different from 1. Only a very small change occurred in correlation between genomic EBV and phenotypes when using the bivariate model. It was always better to genotype all the cows, but when only half of the cows were genotyped, a divergent selection strategy was better compared with the random or directional selection approach. Divergent selection of 30% of the cows remained superior for the yield traits in 8 of 10 folds.     

The stability of preferences for life-sustaining care among persons with AIDS in the Boston Health Study

In 1982, the World Health Organization (WHO) identified inadequate relief from cancer pain as an international health problem. WHO recommended that governments develop and implement national policies and programs for cancer pain relief. This report evaluates national health policy and the systems of health care delivery in relation to cancer pain management in the new South Africa. This field study included multiple methods of data collection: analysis of documents, field trips with participant observation in sites of care delivery, focused interviews, and in-depth interviews of key informants. The purposive sample of key informants (n = 33) represented multiple stakeholders in a variety of settings. Strengths of the developing health policy include specific recommendations related to palliative care; the shift to universal primary care; policies to support drug availability; the inclusion of morphine and codeine as essential drug at the primary health care level; and the development of a national standard related to cancer pain management. Health services are characterized by two parallel systems of care (private and public) with numerous vestiges of the inequities of apartheid. The management of pain varies by provider and setting; major problems with access exist in the rural areas. Health services in South Africa have been plagued by inequity and inadequate resources. New health policies have set a path to ensure universal access to health care including palliative care for cancer. Their successful implementation is the next necessary step toward improving health services and alleviating the suffering of increasing numbers of individuals with cancer.     

Blockade of accumbens 5-HT3 receptor down-regulation by ondansetron administered during continuous cocaine administration

The present experiment examined whether ondansetron, co-administered with continuous cocaine, would block the down regulation of accumbens 5-HT3 receptors. Rats were exposed to a 14-day pretreatment regimen that involved the continuous infusion of 40 mg kg(-1) day(-1) cocaine or 0.9% saline via a subcutaneously implanted osmotic minipump. In addition to the continuous cocaine or saline administration, all subjects received daily subcutaneous (s.c.) injections of either vehicle or 0.1 mg kg(-1) ondansetron for the entire 14-day pretreatment regimen. The rats were then withdrawn from this pretreatment regimen for seven days, and slices from the nucleus accumbens obtained. The slices were perfused with 25 mM K+ in the absence and presence of 0, 12.5, 25, or 50 microM m-Chlorophenyl-biguanide HCl (mCPBG). The efflux samples were assayed for dopamine content by high pressure liquid chromatography (HPLC) with electrochemical detection. Continuous cocaine administration significantly attenuated the ability of mCPBG to facilitate K+-induce dopamine overflow compared to saline control rats. In addition, the rats that received ondansetron and cocaine during the 14-day pretreatment period, the ability of mCPBG to enhance K+ stimulated dopamine release was not significantly different from the saline control subjects. For all groups except the cocaine alone group, the effects of mCPBG on K+ stimulated dopamine release were Ca2+ dependent, suggesting that these effects are receptor mediated. These results suggest that continuous cocaine administration functionally down-regulates 5-HT3 receptors in the nucleus accumbens, and that this down-regulation can be blocked by chronic ondansetron administration. Hence, a functional down regulation of accumbens 5-HT3 receptors represents a significant contribution to the tolerance induced by continuous cocaine administration.     

Identification of seven Treponema species in health- and disease-associated dental plaque by nested PCR

Species-specific nested PCR was used to detect Treponema amylovorum, Treponema denticola, Treponema maltophilum, Treponema medium, Treponema pectinovorum, Treponema socranskii, and Treponema vincentii in dental plaque. Subjects with periodontitis harbored all species, but T. pectinovorum and T. vincentii were not found in plaque from disease-free subjects.     

Gastric and biliary excretion of meperidine in man

The role and importance of enterogastric secretion in the disposition and elimination of the weak base, meperidine (pKa 8.63), was studied after intravenous administration (50 mg) of the drug to 6 normal volunteers. Continuous collection of the gastric fluid over a 4-hr period demonstrated the establishment of high gastric fluid/plasma concentration ratios for meperidine (mean about 50, range, 10 to 200). However, the total amount of drug recovered, even after correction for incomplete collection, was only a small percentage of the administered dose. Under basal conditions a mean +/- SE of 1.9 +/- 0.3 mg, equivalent to 3.7% of the administered dose, was found in the total gastric aspirate. Stimulation of gastric secretion by subcutaneous injection of betazole (1.5 mg/kg) increased this recovery to 3.6 +/- 0.3 mg (7.2%) primarily due to the increase in gastric volumen output. Aspiration of the gastric fluid in either the basal or stimulated situation had no observable effect upon the plasma concentration/time profile of meperidine whether assessed by the terminal half-life, t 1/2 beta, or the plasma clearance; control values were 3.8 +/- hr and 1,190 +/- 130 ml/min, respectively. In 2 subjects "bile fluid" was also collected for 2.5 hr and found to contain less than 0.2% of the administered dose. Enterosystemic recycling is therefore of minor importance in the disposition and elimination of meperidine in man.     

The heroin epidemic in San Francisco: estimates of incidence and prevalence

Much attention has recently been focused on the question of the extent of heroin use in America. In a worthwhile effort to call public attention to the problem, many estimates of its size have evidenced a tendency toward exaggeration and aggrandizement. This paper presents methods of estimation of the extent of heroin addiction which, when carefully employed, should effectively correct such distorted estimates. Two general types of estimation are employed, incidence and prevalence. Incidence estimates are concerned with new cases of heroin addiction that occur in a specific population within a given amount of time. These estimates are based upon self-report data from addicts regarding date of first addiction. When corrected for the "lag phase" (that period of time between onset of first addiction and eventual visit to a treatment program), these data permit accurate retrospective charting of incidence trends. Prevalence estimates focus on all known cases of heroin addiction in a specific population within a given amount of time. Three separate types of prevalence estimates from three separate sources are outlined in this article: estimates based on overdose death data, estimates based on crime statistics, and estimates of "unknown" addicts. In outlining these methods, this article describes the fluctuations in heroin addiction in one major American city, San Francisco, California. After analyzing data gathered from a sample of 2,367 addicts contacted over a 3-year period, this study suggests that the incidence of heroin addiction seems to have declined after 1970. Possible factors underlying this apparent decline in heroin addiction are then discussed, including the post-1970 maturation of the "population at risk," the effectiveness of antidrug media messages, the changing drug fashions in the heroin subculture, and the gradual deterioration of the quality and potency of street heroin.     

BMP signaling plays a role in visceral endoderm differentiation and cavitation in the early mouse embryo

At E4.0 the inner cell mass of the mouse blastocyst consists of a core of embryonic ectoderm cells surrounded by an outer layer of primitive (extraembryonic) endoderm, which subsequently gives rise to both visceral endoderm and parietal endoderm. Shortly after blastocyst implantation, the solid mass of ectoderm cells is converted by a process known as cavitation into a pseudostratified columnar epithelium surrounding a central cavity. We have previously used two cell lines, which form embryoid bodies that do (PSA1) or do not (S2) cavitate, as an in vitro model system for studying the mechanism of cavitation in the early embryo. We provided evidence that cavitation is the result of both programmed cell death and selective cell survival, and that the process depends on signals from visceral endoderm (Coucouvanis, E. and Martin, G. R. (1995) Cell 83, 279-287). Here we show that Bmp2 and Bmp4 are expressed in PSA1 embryoid bodies and embryos at the stages when visceral endoderm differentiation and cavitation are occurring, and that blocking BMP signaling via expression of a transgene encoding a dominant negative mutant form of BMP receptor IB inhibits expression of the visceral endoderm marker, Hnf4, and prevents cavitation in PSA1 embryoid bodies. Furthermore, we show that addition of BMP protein to cultures of S2 embryoid bodies induces expression of Hnf4 and other visceral endoderm markers and also cavitation. Taken together, these data indicate that BMP signaling is both capable of promoting, and required for differentiation of, visceral endoderm and cavitation of embryoid bodies. Based on these and other data, we propose a model for the role of BMP signaling during peri-implantation stages of mouse embryo development.