River wildlife databases and their value for sensitive environmental management

A survey over a 3-year period, which commenced in 1987, of the plant and bird communities along 1200 km of river in Lincolnshire and South Humberside, Eastern England, is described. Analysis of data from 247 km of river recorded a great diversity of wildlife, comprising 570 species of plant and 80 species of breeding birds. The management value of such surveys is discussed and these include the preparation of detailed maps of each 500m section of river, which illustrate the habitat structure, and plant and bird communities. A maintenance procedure for each 500 m section of river is then agreed between conservation and operations personnel, preventing areas of wildlife importance from being accidentally destroyed. An index which combines both the diversity and rarity of the plant and bird communities is proposed as a measure of conservation importance. This index allows sections of river to be graded according to their conservation value into one of five groups. The surveys also enable predictions to be made of the effects of management actions on the wildlife and provide information by which fundamental reviews of operational activities can be carried out.     

Interval and composite interval mapping of somatic cell score,yield, and components of milk in dairy cattle

Single-marker, interval-mapping (IM) and composite interval mapping (CIM) were used to detect quantitative trait loci (QTL) controlling milk, fat and protein yields, and somatic cell score (SCS). A granddaughter design was used to combine molecular genetic information with predicted transmitting abilities (PTA) and estimated daughter yield deviations (DYD) from eight Dairy Bull DNA Repository Holstein families. Models that included and excluded weights accounting for the uncertainty of the response variable were evaluated in each trait, family and phenotype (DYD and PTA) combination. The genotypic information consisted of 174 microsatellite markers along 29 Bos taurus autosomes. The average number of informative markers per autosome was three and the number of informative sons per family and marker varied between 21 and 173. Within-family results from the least squares single-marker analyses were used in expectation-maximization likelihood IM and CIM implemented with QTL Cartographer. Different CIM model specifications, offering complementary control on the background QTL outside the interval under study, were evaluated. Permutation techniques were used to calculate the genome-wide threshold test statistic values based on 1,000 samples. Results from the DYD and PTA analyses were highly consistent across traits and families. The minor differences in the estimates from the models that accounted for or ignored the uncertainty of the DYD (variance) and PTA (inverse of reliability) may be associated to the elevated and consistent precision of the DYD and PTA among sons. The CIM model best supported by the data had 10 markers controlling for background effects. On autosome (BTA) three, a QTL at 32 cM influencing protein yield was located in family five and a QTL at 74 cM for fat yield was located in family eight. Two map positions associated with SCS were detected on BTA 21, one at 33 cM in family one and the other at 84 cM in family three. A QTL for protein yield was detected between 26 and 36 cM on BTA six, family six, and a QTL for milk yield was detected at 116 cM on BTA seven in family three. The IM and CIM approaches detected a QTL at 3 cM on BTA 14 influencing fat yield in family four. Two map positions on BTA 29 were associated with significant variation of milk (0 cM) and fat yield (14 cM) in family seven. These results suggest the presence of one QTL with pleiotropic effects on multiple traits or multiple QTL within the marker interval. Findings from this study could be used in subsequent fine-mapping work and applied to marker-assisted selection of dairy production and health traits.     

Validity of conventional approaches for calculating body currentsresulting from electric shocks

In North America, ANSI/IEEE Standard 80 is almost universally applied to determine electrical currents flowing through the human body as the result of touch and step voltages near transmission and distribution facilities. The authors argue that significant inaccuracies can occur when the ANSI/IEEE Standard 80 based method is applied without understanding the assumptions which underlie it. In particular, errors can occur when the method is applied to grounding situations where the remote foot resistance of a human is much different from the resistance through ground between a human's feet and the buried grounding system under study. The authors discuss the problem of determining body currents from measured touch voltages and present an improved model for doing so     

Detection of quantitative trait loci influencing dairy traits using a model for longitudinal data

A longitudinal-linkage analysis approach was developed and applied to an outbred population. Nonlinear mixed-effects models were used to describe the lactation patterns and were extended to include marker information following single-marker and interval mapping models. Quantitative trait loci (QTL) affecting the shape and scale of lactation curves for production and health traits in dairy cattle were mapped in three U.S. Holstein families (Dairy Bull DNA Repository families one, four, and five) using the granddaughter design. Information on 81 informative markers on six Bos taurus autosomes (BTA) was combined with milk yield, fat, and protein percentage and somatic cell score (SCS) test-day records. Six percent of the single-marker tests surpassed the experiment-wise significance threshold. Marker BL41 on BTA3 was associated with decrease in milk yield during mid-lactation in family one. The scale and shape of the protein percentage lactation curve in family four varied with BMC4203 (BTA6) allele that the son received from the grandsire. Some map locations were associated with variation in the lactation pattern of multiple traits. In family four, the marker HUJI177 (BTA3) was associated with changes in the milk yield and protein percentage curves suggesting a QTL with pleiotropic effects or multiple QTL in the region. The interval mapping model uncovered a QTL on BTA7 associated with variation in milk-yield pattern in family four and a QTL on BTA21 affecting SCS in family five. The developed approach can be extended to random regressions, covariance functions, spline, gametic and variance component models. The results from the longitudinal-QTL approach will help to understand the genetic factors acting at different stages of lactation and will assist in positional candidate gene research. Identified positions can be incorporated into marker-assisted selection decisions to alter the persistency and peak production or the fluctuation of SCS during a lactation.     

The histologic phenotypes of breast carcinoma occurring before age 40 years in women with and without BRCA1 or BRCA2 germline mutations: a population-based study

BACKGROUND: Women with breast carcinoma diagnosed before age 40 years have a greater prevalence of germline BRCA1 and BRCA2 mutations than women with breast carcinoma diagnosed at older ages. Several recognizable histologic characteristics have been identified in breast carcinoma from studies of BRCA1/2 mutation carriers who belong to multiple-case families. The authors attempted to determine whether breast carcinoma occurring before age 40 years in BRCA1 or BRCA2 mutation carriers who were not selected for family history could be distinguished histologically from one another and from breast carcinoma in women of a similar age without a germline BRCA1 or BRCA2 mutation. METHODS: The study undertook a histologic assessment of breast carcinomas diagnosed before age 40 years identified from a population-based study. RESULTS: Breast carcinoma in BRCA1 mutation carriers was associated with a distinct histologic appearance; these tumors were high grade, and had exceptionally high mean mitotic counts, a syncytial growth pattern, pushing margins, and confluent necrosis. Atypical medullary carcinoma was overrepresented in BRCA1 mutation carriers. All low grade tumors and tumors with low mitotic rates belonged to the group without BRCA1 or BRCA2 mutations. Pleomorphic lobular carcinomas and extensive intraduct carcinomas were more common in BRCA2 mutation carriers. CONCLUSIONS: Breast carcinoma occurring in women with a germline BRCA1 or BRCA2 mutation have recognizable histologic phenotypes, which may be useful in identifying individuals more likely to carry germline mutations. Histologic examination of breast carcinoma should become an important part of the evaluation of women seeking genetic testing for germline mutations in these breast carcinoma susceptibility genes.     

Metric-Based Methods for Adaptive Model Selection and Regularization

We present a general approach to model selection and regularization that exploits unlabeled data to adaptively control hypothesis complexity in supervised learning tasks. The idea is to impose a metric structure on hypotheses by determining the discrepancy between their predictions across the distribution of unlabeled data. We show how this metric can be used to detect untrustworthy training error estimates, and devise novel model selection strategies that exhibit theoretical guarantees against over-fitting (while still avoiding under-fitting). We then extend the approach to derive a general training criterion for supervised learning—yielding an adaptive regularization method that uses unlabeled data to automatically set regularization parameters. This new criterion adjusts its regularization level to the specific set of training data received, and performs well on a variety of regression and conditional density estimation tasks. The only proviso for these methods is that sufficient unlabeled training data be available.     

Effective short-term opponent exploitation in simplified poker

Uncertainty in poker stems from two key sources, the shuffled deck and an adversary whose strategy is unknown. One approach to playing poker is to find a pessimistic game-theoretic solution (i.e., a Nash equilibrium), but human players have idiosyncratic weaknesses that can be exploited if some model or counter-strategy can be learned by observing their play. However, games against humans last for at most a few hundred hands, so learning must be very fast to be useful. We explore two approaches to opponent modelling in the context of Kuhn poker, a small game for which game-theoretic solutions are known. Parameter estimation and expert algorithms are both studied. Experiments demonstrate that, even in this small game, convergence to maximally exploitive solutions in a small number of hands is impractical, but that good (e.g., better than Nash) performance can be achieved in as few as 50 hands. Finally, we show that amongst a set of strategies with equal game-theoretic value, in particular the set of Nash equilibrium strategies, some are preferable because they speed learning of the opponent’s strategy by exploring it more effectively. Electronic Supplementary Material  The online version of this article () contains supplementary material, which is available to authorized users.     

Pathophysiological role of nitric oxide in rat experimental colitis

Overproduction of nitric oxide (NO) by inducible nitric oxide synthase (iNOS) may contribute to the pathophysiology of ulcerative colitis. A 2,4,6-trinitrobenzenesulfonic acid sodium salt (TNBS) colitis model was established to examine the effect of selective iNOS inhibition, by S-(2-aminoethyl) isothiouronium bromide (ITU), on colonic mucosal cell damage and inflammation. Rats, killed 7 days after TNBS, had increased colonic mucosal levels of iNOS and interleukin-8 (IL-8), in addition to severe colonic inflammation which was characterized by significantly increased colon weight, damage score and colonic myeloperoxidase activity (MPO) (a marker of neutrophil influx). TNBS-treated rats had markedly decreased body weight and thymus weight. Administration of colitic rats with ITU significantly inhibited iNOS activity/expression and tended to reduce mucosal levels of IL-8, but no effect on MPO activity was observed. Following ITU therapy, colitic rats had reduced colonic damage and losses in body weight and thymus weight were reversed. Improvement of TNBS colitis by ITU suggested that excess NO, produced by iNOS, may have contributed to the initiation/amplification of colonic disease, by mechanisms including enhancement of IL-8 release. NO-mediated enhancement of pro-inflammatory cytokine release was further investigated in vitro. Lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) stimulated release of nitrite, lactate dehydrogenase (LDH), TNF alpha, IL-1 beta and IL-8 from rat peritoneal macrophages, all of which were significantly reduced by ITU. This suggests that NO-mediated cell damage enhances pro-inflammatory mediator release from macrophages. In addition, enhancement of IL-8 and TNF alpha release was also partially NO-dependent in activated peritoneal neutrophils. Therefore, the amelioration of TNBS colitis by ITU could include inhibition of NO-mediated pro-inflammatory cytokine release.