This study examines tissues from sequential-kill, time-course pathogenesis studies to refine estimates of the age at which disease-specific PrP (PrPSc) can first be detected in the central nervous ...system (CNS) and related peripheral nervous system ganglia of cattle incubating bovine spongiform encephalopathy (BSE). Such estimates are important for risk assessments of the age at which these tissues should be removed from cattle at slaughter to prevent human and animal exposure to BSE infection. Tissues were examined from cattle dosed orally with 100 or 1 g BSE-infected brain. Incubation period data for the doses were obtained from attack rate and the sequential-kill studies. A statistical model, fitted by maximum likelihood, accounted for the differences in the lognormal incubation period and the logistic probability of infection between different dose groups. Initial detection of PrPSc during incubation was invariably in the brainstem and the earliest was at 30 and 44 months post-exposure for the 100 g- and 1 g-dosed sequential-kill study groups, respectively. The point at which PrPSc in 50 % of the animals would be detected by immunohistochemistry applied to medulla-obex was estimated at 9.6 and 1.7 months before clinical onset for the 100 g- and 1 g-dosed cattle, respectively, with a low probability of detection in any of the tissues examined at more than 12 months before clinical onset. PrPSc was detected inconsistently in dorsal root ganglia, concurrent with or after detection in CNS, and not at all in certain sympathetic nervous system ganglia.
The well-known general problem of signal detection in background interference is addressed for situations where a certain statistical description of the interference is unavailable, but is replaced ...by the observation of some secondary (training) data that contains only the interference. For the broad class of interferences that have a large separation between signal-and noise-subspace eigenvalues, we demonstrate that adaptive detectors which use a diagonally loaded sample covariance matrix or a fast maximum likelihood (FML) estimate have significantly better detection performance than the traditional generalized likelihood ratio test (GLRT) and adaptive matched filter (AMI') detection techniques, which use a maximum likelihood (ML) covariance matrix estimate. To devise a theoretical framework that can generate similarly efficient detectors, two major modifications are proposed for Kelly's traditional GLRT and AMF detection techniques. First, a two-set GLRT decision rule takes advantage of an a priori assignment of different functions to the primary and secondary data, unlike the Kelly rule that was derived without this. Second, instead of ML estimates of the missing parameters in both GLRT and AMF detectors, we adopt expected likelihood (EL) estimates that have a likelihood within the range of most probable values generated by the actual interference covariance matrix. A Gaussian model of fluctuating target signal and interference is used in this study. We demonstrate that, even under the most favorable loaded sample-matrix inversion (LSMI) conditions, the theoretically derived EL-GLRT and FL-AMF techniques (where the loading factor is chosen from the training data using the EL matching principle) gives the same detection performance as the loaded AMF technique with a proper a priori data-invariant loading factor. For the least favorable conditions, our EL-AMF method is still superior to the standard AMF detector, and may be interpreted as an intelligent (data-dependent) method for selecting the loading factor.
Two experiments (E1, E2) were conducted to compare the influence of sires (sire A on dam C vs. sire B on dam C) and straight-run versus sex-separate rearing on the incidence of bacterial ...chondronecrosis with osteomyelitis (BCO) in broilers. Fertile eggs from commercial breeder flocks were incubated and hatched at the University of Arkansas Poultry Research Hatchery. Male and female chicks were reared together (straight-run) or separately (sex-separate) in 3 × 3 m pens on litter or flat wire flooring with 65 (E1) or 60 (E2) birds per pen. Necropsies revealed lesions that are pathognomonic for BCO in ≥98% of the birds that became lame. The SigmaStat Z-test was used to compare cumulative BCO incidences through 8 wk of age. For birds reared on litter, the incidences of BCO were low regardless of cross or sex (range: 1.7 to 5.1%; P ≥ 0.6). Within a cross and sex, rearing the broilers straight-run versus sex-separate on wire flooring did not significantly affect the incidence of BCO. Significant incidences of BCO did not develop until after d 40. Males from the sire A cross developed a higher incidence of BCO than males from the sire B cross in E1 (27 vs. 17%, respectively; P = 0.009) but not in E2 (28.5 vs. 22.6%, respectively; P = 0.141). In both experiments, males from the sire A cross developed higher incidences of BCO than females from the sire B cross (27 vs. 11.9%, in E1; 28.5 vs. 14.8%, in E2). With the sexes pooled, broilers from the sire A cross consistently developed higher incidences of BCO than broilers from the sire B cross (21.4 vs. 14.9%, P = 0.005 in E1; 26.5 vs. 18.7%, P = 0.003 in E2). High susceptibilities to both femoral head (all femoral head necrosis = 66 to 85% incidences) and tibial head (all tibial head necrosis = 81 to 96% incidences) BCO lesions were demonstrated in lame birds from both sexes and crosses. This study supports a sire influence on the susceptibility of broilers to BCO. Sire lines can be chosen to reduce BCO susceptibility when broilers are grown beyond 6 wk of age.
We consider the adaptive radar problem where the properties of the (nonstationary) clutter signals can be estimated using multiple observations of radar returns from a number of sufficiently ...homogeneous range/azimuth resolution cells. We derive a method for approximating an arbitrary Hermitian covariance matrix by a time-varying autoregressive model of order m, TVAR(m), that is based on the Dym-Gohberg band-matrix extension technique which gives the unique TVAR(m) model for any nondegenerate covariance matrix. We demonstrate that the Dym-Gohberg transformation of the sample covariance matrix gives the maximum-likelihood (ML) estimate of the TVAR(m) covariance matrix. We introduce an example of TVAR(m) clutter modeling for high-frequency over-the-horizon radar that demonstrates its practical importance
The immunohistochemical localisation of the disease-specific protein, PrPSc, was examined in the distal ileum of cattle up to 40 months after they had been exposed orally to the agent of bovine ...spongiform encephalopathy (BSE), in the intestines and mesenteric lymph nodes of an additional group of cattle, killed six months after a similar exposure, and in the distal ileum of naturally occurring clinical cases of BSE. PrPSc was detected, mainly in macrophages, in a small proportion of the follicles of Peyer's patches in the distal ileum of the experimentally exposed cattle throughout much of the course of the disease. The observations are in agreement with the infectivity data derived from mouse bioassays of the distal ileum. At the later stages of the disease, the proportion of immunostained follicles increased as the total number of follicles decreased with age. In the additional experimental group of cattle, PrPSc was confined to the Peyer's patches in the distal ileum. No immunostaining was detected in the lymphoid tissue of the distal ileum of naturally occurring clinical cases of BSE. In some of the clinically affected experimentally induced and naturally occurring cases of BSE there was sparse immunostaining of the neurons of the distal ileal myenteric plexus.
Since early 2014, several outbreaks involving novel reassortant highly pathogenic avian influenza (HPAI) A(H5N8) viruses have been detected in poultry and wild bird species in Asia, Europe and North ...America. These viruses have been detected in apparently healthy and dead wild migratory birds, as well as in domestic chickens, turkeys, geese and ducks. In this study, we describe the pathology of an outbreak of H5N8 HPAIV in breeder ducks in the UK. A holding with approximately 6000 breeder ducks, aged approximately 60 weeks, showed a gradual reduction in egg production and increased mortality over a 7‐day period. Post‐mortem examination revealed frequent fibrinous peritonitis, with severely haemorrhagic ovarian follicles and occasional splenic and pancreatic necrosis and high incidence of mycotic granulomas in the air sacs and lung. Low‐to‐moderate levels of HPAI H5N8 virus were detected mainly in respiratory and digestive tract, with minor involvement of other organs. Although histopathological examination confirmed the gross pathology findings, intralesional viral antigen detection by immunohistochemistry was not observed. Immunolabelled cells were rarely only present in inflamed air sacs and serosa, usually superficial to granulomatous inflammation. Abundant bacterial microcolonies were observed in haemorrhagic ovaries and oviduct. The limited viral tissue distribution and presence of inter‐current fungal and bacterial infections suggest a minor role for HPAIV H5N8 in clinical disease in layer ducks.
The problem of estimating the number of independent Gaussian sources and their parameters impinging upon an antenna array is addressed for scenarios that are problematic for standard techniques, ...namely, under "threshold conditions" (where subspace techniques such as MUSIC experience an abrupt and dramatic performance breakdown). We propose an antenna geometry-invariant method that adopts the generalized-likelihood-ratio test (GLRT) methodology, supported by a maximum-likelihood-ratio lower-bound analysis that allows erroneous solutions ("outliers") to be found and rectified. Detection-estimation performance in both uniform circular and linear antenna arrays is shown to be significantly improved compared with conventional techniques but limited by the performance-breakdown phenomenon that is intrinsic to all such maximum-likelihood (ML) techniques
Further preliminary observations are reported of an experiment to examine the spread of infectivity and the occurrence of pathological changes in cattle exposed orally to infection with bovine ...spongiform encephalopathy. Calves were dosed at four months of age and clinically monitored groups were killed sequentially from two to 40 months after inoculation. Tissues were collected for bioassay, for histopathological examinations and for the detection of PrP. Previous reported observations have included the presence of infectivity in the distal ileum of cattle killed after six to 18 months, the earliest onset of clinical signs in an exposed animal after 35 months, and diagnostic histopathological changes in the brain, in association with clinical disease, after 36, 38 and 40 months. In spite of the relative inefficiency of the bioassay of scrapie-like agents across a species barrier the new observations confirm that the onset of clinical signs and pathological changes in the central nervous system (CNS) occur at approximately the same time. The earliest pathological change, the presence of abnormal PrP 32 months after inoculation, coincided with the earliest detected infectivity in the CNS and occurred shortly before there was evidence of typical spongiform changes in the brain 36 months after inoculation. Infectivity has now been demonstrated in the peripheral nervous system, in the cervical and thoracic dorsal root ganglia 32 to 40 months after inoculation and in the trigeminal ganglion 36 and 38 months after inoculation. At the time of writing evidence of infectivity in other tissues is confined to the distal ileum, not only after six to 18 months but also after 38 and 40 months, but these findings may be supplemented by the results of further mouse assays. Nevertheless, they are in general agreement with current knowledge of the pathogenesis of scrapie.
The multiple hypothesis testing problem of the detection-estimation of an unknown number of independent Gaussian point sources is adequately addressed by likelihood ratio (LR) maximization over the ...set of admissible covariance matrix models. We introduce nonasymptotic lower and upper bounds for the maximum LR. Since LR optimization is generally a nonconvex multiextremal problem, any practical solution could now be tested against these bounds, enabling a high probability of recognizing nonoptimal solutions. We demonstrate that in many applications, the lower bound is quite tight, with approximate maximum likelihood (ML) techniques often unable to approach this bound. The introduced lower bound analysis is shown to be very efficient in determining whether or not performance breakdown has occurred for subspace-based direction-of-arrival (DOA) estimation techniques. We also demonstrate that by proper LR maximization, we can extend the range of signal-to-noise ratio (SNR) values and/or number of data samples wherein accurate parameter estimates are produced. Yet, when the SNR and/or sample size falls below a certain limit for a given scenario, we show that ML estimation suffers from a discontinuity in the parameter estimates: a phenomenon that cannot be eliminated within the ML paradigm.
For a set of T independent observations of the same N-variate correlated Gaussian process, we derive a method of estimating the order of an autoregressive (AR) model of this process, regardless of ...its stationary or time-varying nature. We also derive a test to discriminate between stationary AR models of order m,AR(m), and time-varying autoregressive models of order m,TVAR(m). We demonstrate that within this technique the number T of independent identically distributed data samples required for order estimation and discrimination just exceeds the maximum possible order m max , which in many cases is significantly fewer than the dimension of the problem N
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