Risk-based strategies for surveillance of tuberculosis infection in cattle for low-risk areas in England and Scotland.

Disease surveillance can be made more effective by either improving disease detection, providing cost savings, or doing both. Currently, cattle herds in low-risk areas (LRAs) for bovine tuberculosis (bTB) in England are tested once every 4 years. In Scotland, the default herd testing frequency is also 4 years, but a risk-based system exempts some herds from testing altogether. To extend this approach to other areas, a bespoke understanding of at-risk herds and how risk-based surveillance can affect bTB detection is required. Here, we use a generalized linear mixed model to inform a Bayesian probabilistic model of freedom from infection and explore risk-based surveillance strategies in LRAs and Scotland. Our analyses show that in both areas the primary herd-level risk factors for bTB infection are the size of the herd and purchasing cattle from high-risk areas of Great Britain and/or Ireland. A risk-based approach can improve the current surveillance system by both increasing detection (9% and 7% fewer latent infections), and reducing testing burden (6% and 26% fewer animal tests) in LRAs and Scotland, respectively. Testing at-risk herds more frequently can also improve the level of detection by identifying more infected cases and reducing the hidden burden of the disease, and reduce surveillance effort by exempting low-risk herds from testing.

Are the electroencephalograms mainly rhythmic? Assessment of periodicity in wide-band time series.

To test the hypotheses that (i). electroencephalograms (EEGs) are largely made up of oscillations at many frequencies and (ii). that the peaks in the power spectra represent oscillations, we applied a new method, called the period specific average (PSA) to a wide sample of EEGs. Both hypotheses can be rejected. Although the principal peaks in the two spectra agree most of the time, quite often a peak in the power spectrum accompanies no periodicity peak and some periodicity peaks have no power spectral peak. The Fourier spectrum is not a reliable indication of rhythms. EEG samples from patients during waking, sleeping and seizure states, and volunteer healthy subjects doing cognitive tasks quite often show no significant rhythms, on an arbitrary, common sense definition. When clear rhythms are seen, they involve one or two, rarely up to four or five simultaneous non-harmonically related frequencies. Rhythms are special cases; most of the power spectrum most of the time is nonrhythmic. "Good" rhythms usually have quite narrow peaks, with frequency modulation of <5%, strengths of >2.5 up to >10 times the expectation from chance, and they often show fine structure by being quite local and brief. Most rhythms are quasisinusoidal but others are sharp-cornered recurrent events with <50% duty cycle. In the face of wide variability, we do not report any systematic differences in periodicity among EEGs from different parts of the brain or different brain states or species; it will take many more exemplars of each state, species or brain part to establish characteristic features. The PSA method may be the best so far proposed to demonstrate and quantify periodicity in wide-band time series with noise, but it has serious limitations. Discussion leads to the conclusion that it is time for a new paradigm or metaphor for brain waves.

Monocularly programmed human saccades during vergence changes?

1. When binocular fixation is shifted to a new target located at a different distance and in a different direction from initial fixation, a binocularly unbalanced saccade occurs at or near the onset of the composite eye movement. Those saccades typically produce good post-saccadic foveation of the target by one eye or the other. 2. Following such saccades, the better-aligned eye is typically as well aimed at the target as after pure versional saccades, but the partner eye deviates much more, thus requiring asymmetrical post-saccadic vergence movement. 3. This phenomenon suggests that during binocular viewing, the retinal eccentricity of a new-target's image from one of the eyes can be used to programme that eye's own saccade, so that it arrives reliably on target; and that the images of that target from both eyes participate in generating the saccadic excursion of the partner eye. 4. The ecologically useful result is rapid achievement of a high-resolution monocular view of the new target, although full binocular foveation is achieved much later.

On the "cyclopean eye": saccadic asymmetry and the reliability of perceived straight-ahead.

If two targets are both on the visual axis of one eye or the other, and binocular fixation is shifted from the farther one to the nearer, the aligned eye consistently makes an initial, seemingly pointless saccade in a temporal direction. The size of those saccades typically differs markedly, depending on whether the targets are aligned with the observer's dominant or non-dominant eye. Pickwell [(1972) Vision Research, 12, 1499-1507] proposed that this binocular asymmetry in oculomotor performance reflects a subject-specific lateral displacement of the egocenter (the "binoculus" of Hering, which has traditionally been assumed to be on the midline). An empirical test of Pickwell's widely endorsed hypothesis has now been conducted and the proposal has been found wanting. In an otherwise darkened room, subjects were required repeatedly to set a small light to a perceived straight-ahead location in the horizontal plane, first for a target at 300 cm distance and then for one at 30 cm. Extrapolation of a line that connects the two averages of those settings to the inter-ocular axis provides an estimate of the subjective egocenter to which visual directions are referred. Contrary to Pickwell's proposal, those locations of the inferred egocenter were usually quite near the midline, and were completely uncorrelated with same-subject data on the extent of saccadic asymmetry at the onset of asymmetrical convergence. The data on perceived straight-ahead underlying this result indicate the availability of extraretinal information about eye orientation that is quite precise at a given moment (median standard deviation of 47 min arc) but conspicuously non-stationary over several-minute intervals (monotonic drifts in sequential settings being very common).

Slow-velocity asymmetrical convergence: a decisive failure of "Hering's law".

With targets aligned in the midsagittal plane, six of seven subjects tested were often able to make smooth symmetrical convergence movements in which no detectable saccade occurred during the initial 300 msec of the eye movement (12-95% of their trials). With targets located in a plane parallel to, but appreciably to one side of the midsagittal plane, those same six subjects were also often able to make smooth, slow, "saccade-free" asymmetrical convergence movements that were appropriate in magnitude and velocity to the target location (ratio of excursions about 2 to 1). Vergence movements are thus more versatile than can be accounted for by a single generator of binocularly symmetrical input to the eye muscles (Hering's Law of Equal Innervation). The occurrence of "saccade-free" asymmetrical convergence suggests instead that during binocular viewing, each eye can respond independently to that eye's view of the target, resulting in binocularly simultaneous slow-velocity nasalward eye movements--which will represent symmetrical or asymmetrical convergence depending on the arrangement of the targets. A similar interpretation is also apparently demanded by recent data on the initiation of disjunctive smooth-pursuit movements in the monkey [King & Zhou (1995) Vision Research, 35, 3389-3400].

Sequential stereopsis: a simple demonstration.

Most people strongly prefer to use back-and-forth eye movements in order to discriminate 3-dimensional distances among targets that are widely separated from each other in direction. This viewing strategy permits sequential stereopsis: a comparison between the foveally-seen pre-saccadic disparity of one target with post-saccadic disparity of the other. This note describes a simple and qualitatively compelling demonstration of the usefulness of sequential stereopsis, in a situations in which classical stereopsis, with steady fixation, is greatly degraded. Targets of high-spatial-frequency texture are used, with details that can be resolved foveally before and after saccades, but that are unresolvable in peripheral vision. Back-and-forth eye movements between such textured targets, separated by 8-10 deg from each other, led to estimates of threshold that average less than 45 sec arc disparity (corresponding to about 0.18% of viewing distance): some of the best performances ever reported for targets so widely separated.

Postmortem tissue samples: an alternative to urine and blood for drug analysis in racehorses.

Although urine is the sample of choice for drug tests in racehorses, it is rarely obtained following the sudden death of a racehorse on the track while racing. The purpose of this study was to demonstrate the significance of postmortem tissue samples as an alternative to urine and blood samples in equine drug analysis following the sudden death of a racehorse on the track while participating in a competitive race. Postmortem tissue samples were frozen (-80 degrees C) until analyzed. A 30-40-g portion of each organ was homogenized in a 0.1 M phosphate buffer (pH 7.4), deproteinized, hydrolyzed with beta-glucuronidase, extracted, and screened by thin-layer chromatography and immunoassay. Samples that initially tested positive for drug(s) were then extracted using high-flow, solid-phase extraction cartridges. The eluates were analyzed by gas chromatography-mass spectrometry. The presence of butorphanol in horses HB355 and CD387, pentobarbital in horse HO940, and ergotamine in horses HO940 and CD387 was detected and confirmed. Thus, in the absence of urine and blood samples following sudden death, postmortem tissue samples are equally useful for forensic toxicological investigations of racehorses.

The non-visual impact of eye orientation on eye-hand coordination.

When a peripheral visual stimulus is briefly presented in an empty surround, and an observer is required, after a delay of a few seconds, to point toward the remembered location of that target, the responses are strongly influenced by eye orientation at the time of pointing. Remembered locations, as indicated in total darkness, are typically more precise (more reproducible across trials) when the subject's eyes are aimed toward the target before pointing, than when initial fixation (straight ahead) is maintained during pointing. Furthermore, when the eyes are aimed toward the target, the indicated directions are usually biased toward less eccentric locations than those indicated with eyes aimed straight ahead. These differences in scatter and in bias arise regardless of whether the eye movement toward target location, which precedes pointing, is made while the target is visible or occurs thereafter in total darkness, thus demonstrating that non-visual stimuli associated with eye orientation affect the spatial memory used by the skeletal muscle system.

To stare or to scrutinize: "grasping" the eye for better vision.

Words of a rich variety exist for describing the different ways of "looking" at a target; and one of the major dimensions for such differentiation is the spectrum between staring and scrutinizing, between gazing and peering. This dimension seems primarily to reflect the level of attention given to details of the visual stimuli: a "cognitive" distinction. Evidence now demonstrates that staring and scrutiny also differ in the net muscular forces exerted on the eye; during scrutiny, opposing pairs of rectus muscles apparently jointly contract pulling the eye somewhat backward into its orbit, while it stays aimed in the same direction.

Mach bands and airplane shadows cast on dry terrain.

Luminous rings are often seen surrounding the shadow of a high-flying airplane. Some of these phenomena are due to water droplets (glories, the Heiligenschein), but a different sort of explanation is required when a luminous ring (sometimes simply a bright spot) is seen while the plane is flying over dry terrain. Demonstrations involving distances and shadows manyfold smaller than those of an airliner's shadow show that Mach bands can produce illusory luminance phenomena that greatly resemble those associated with a plane's shadow over dry terrain. Luminance rings have recently also been observed over dry, sparsely vegetated terrain, around the shadow of an adjacent airplane (i.e., far from the observer's antisolar point), thereby excluding all previous alternative interpretations; Mach bands are thus a likely explanation for at least some instances of dry-terrain luminous rings around airplane shadows.

The remarkable saccades of asymmetrical vergence.

The saccades that usually arise near the onset of asymmetrical changes in vergence, when one eye is aligned with both targets, are remarkably different from ordinary saccades: (1) the excursions of the two eyes are typically very unequal, often differing by several fold from each other; (2) mean excursion (version) is extremely variable across replicate tests with identical targets; (3) at the end of the saccades, eye orientation is usually not even briefly stable: the aligned eye immediately reverses its movement, indicating that the pulse in muscular forces is apparently not followed by a corresponding step; and (4) a second saccade in the opposite direction can immediately follow the initial saccade of asymmetrical divergence, with no sign of refractoriness. These phenomena suggest that the pulse and step components of saccadic motoneuron activity may be generated by largely independent processes; that the step component for each eye depends only on that eye's visual input; and that the pulse components generated for each eye depend on weighted averaging of visual stimuli that impinge on both eyes. This interpretation is incompatible with most current models of saccade generation, but was anticipated in its essentials by Ditchburn [(1973) Eye movements and visual perception. Oxford: Clarendon Press]. A corollary of this hypothesis is that disparity-evoked vergence changes can be viewed as the general-case output from that system which produces fully conjugate saccades as a special case.

Unexpected role of the oblique muscles in the human vertical fusional reflex.

1. If a weak vertically oriented prism is inserted before one eye, binocular single vision is restored by vertically divergent eye movements (one eye turning upward, the other downward); and it is usually assumed that the vertical rectus muscles mediate that fusional reflex. 2. When vertically divergent eye movements occur, both eyes also systematically rotate in parallel around their lines of sight (conjugate cyclotorsion). The direction of these unexpected eye movements demonstrates that they must be due to the oblique muscles, not the vertical recti. 3. The magnitude of these conjugate torsional movements is large enough to imply that the oblique muscles, in producing such torsion, would simultaneously effect all the divergent vertical re-orientation of the eyes required by the targets. 4. The cyclotorsion is accompanied by systematic translation of the eye along a nasal-temporal axis; the direction and extent of that non-rotational displacement indicate that the eye movements of the fusional reflex may well be mediated exclusively by the superior oblique muscles, acting against fixed tone in the inferior oblique muscles. 5. This revised understanding of the oculomotor co-ordination involved in the vertical fusional reflex has significant implications for both neurophysiology and oculomotor surgery.

Exploring the third dimension with eye movements: better than stereopsis.

Eye movements are usually presumed to be irrelevant for (or detrimental to) stereoacuity. When targets of interest are not adjacent, however, better discrimination of distance can be achieved by looking back and forth between them. In order to exclude ordinary stereopsis and examine this viewing strategy in isolation, judgements of apparent equidistance have been obtained for pairs of small targets separated horizontally by the angular spacing that corresponds to the fovea-to-blind-spot distance. Precise, stereopsis-like evaluations of relative distance can be made by fixating each of those targets in turn, even if they are not simultaneously presented but are instead shown in alternation. Sequential comparisons of stimuli are thus involved in this form of distance discrimination, but direct utilization of oculomotor information (vergence) is rendered unlikely because very brief target presentation is sufficient. Hence, the evidence argues for "sequential stereopsis": comparisons of the disparities of targets, both seen foveally, before and after saccades. This interpretation makes stringent demands on oculomotor coordination during saccades, but measurements of vergence "noise" indicate that this requirement can probably be fulfilled.

Stereo-thresholds: simultaneity, target proximity and eye movements.

Stereo-thresholds are much higher when adjacent targets are presented without temporal overlap than when they are shown simultaneously. Sequentially presented adjacent targets also evoke small involuntary eye movements toward the newly presented target. Neither of these phenomena is evident with widely separated targets; for sequential presentation of targets 10 degrees apart, stereo-thresholds are only slightly higher (a factor of about 1.5) than for simultaneous presentation; and stable fixation can be maintained. If the differing influence of simultaneity on stereoacuity for adjacent and for widely separated targets arises because adjacent alternating targets evoke eye movements, that effect is apparently not mediated exclusively by displacement of retinal images due to the measured eye movements. It could, however, be due to a general long-term instability of fixation associated with repetitive small involuntary eye movements.

Ceroid accumulation by murine peritoneal macrophages exposed to artificial lipid-containing particles: the role of the hydrophilic component.

Murine resident peritoneal macrophages were maintained in cell culture in a medium containing 10% lipoprotein-deficient foetal calf serum to which various artificial lipid-containing particles were added. These had a core of oxidizable lipid, generally cholesteryl linoleate, and were stabilized in aqueous suspension by one of a variety of poly-L-amino acids, proteins or polysaccharides. Most particles, except those containing poly-L-lysine or poly-L-arginine (both strongly basic), were readily taken up by the macrophages to form typical ceroid inclusions, the morphological form of which was determined by the nature of the core lipid. The hydrophilic stabilizing component seemed largely irrelevant in this respect. The role of the latter appears largely to be to allow the cellular uptake of lipid, although it may also participate in ceroid formation.

Macrophages and ceroid in human atherosclerosis.

It is proposed that atherosclerosis is a chronic inflammatory disease in which monocyte-derived macrophages are doing harm and smooth muscle cells are essentially reparative. Activities of macrophages that might be contributory to the development of atherosclerosis are tabulated. Observations and experiments are described that suggest macrophages may be contributing to lipoprotein oxidation within the plaque and that individual humans vary in their macrophage oxidative capacity. The possibility of intervention with antioxidants is discussed.

Oxidation of cholesteryl linoleate by human monocyte-macrophages in vitro.

The amount of cholest-5-en-3 beta,7 beta-diol (CD) was significantly higher in cultures of human monocytes incubated with cholesteryl linoleate-bovine serum albumin (CL/BSA) artificial lipoproteins than in no-cell control incubations of CL/BSA. CD production by monocytes was almost completely inhibited by the radical scavengers butylated hydroxytoluene (BHT), probucol, and alpha-tocopherol, and was partially inhibited by the metal chelator EDTA. The production of CD was accompanied by decrease in linoleic acid. CD amounts were negligible in incubations of monocytes with cholesteryl oleate/BSA (CO/BSA) or cholesterol/BSA (C/BSA). Ability to produce CD from CL/BSA appeared to increase with age in culture of human monocyte-macrophages. Considerable variations were observed in the CD production from CL/BSA by monocytes from different blood donations. Higher levels of CD production appeared more common with monocytes from men than from women. The significance of these results in the context of human atherosclerosis is discussed.

Stereopsis, cyclotorsional "noise" and the apparent vertical.

In principle, stereopsis can be used to evaluate the subjective vertical in a sagittal plane, but temporal variation in cyclotorsion should degrade that ability. Video recordings of eye orientation during steady fixation were used to evaluate long-term instability in cyclotorsion. Torsion was measured simultaneously in each eye at 1-sec intervals during about 30 sequential fixations (5-sec duration) on the same target. For each eye separately, the standard deviation of torsion around its mean value averaged about 18 min arc. Some of this variation was conjugate, but the variability in torsional difference between the eyes averaged 17 min arc. Most of this second-to-second variation arose between fixations (average SD = 15 min arc). Such low-frequency, inter-fixational variation in torsional difference between the eyes must produce spurious horizontal disparities in the upper and lower visual fields, and should thereby limit the precision with which the vertical horopter can be evaluated. All subjects exceeded those theoretical limits on precision, however, in performance tests requiring that two vertically separated targets be adjusted to apparent equidistance--but only when permitted to shift fixation back and forth between the upper and lower targets. That latter result provides a challenge to current understanding of stereopsis.

Convergence during human vertical saccades: probable causes and perceptual consequences.

1. When a downward saccade is made between equidistant targets, convergence consistently occurs during the saccade: about 1 deg overconvergence after an 8 deg saccade, with either binocular or monocular viewing, with either far (3 m) or near (30 cm) viewing distance. 2. During binocular viewing, this unnecessary convergence is corrected by divergence movement with a half-time of about 200 ms. During monocular viewing of far targets, similar post-saccadic divergence occurs, but for monocularly-seen near targets, recovery is considerably slower. 3. Vergence changes associated with upward saccades are much smaller and typically more variable among subjects. 4. The up-down asymmetry of intrasaccadic vergence changes can be accounted for by superposition of two plausible adventitious processes: co-contraction of the vertical recti, and tension increase (upward saccades) or tension release (downward saccades) in the superior oblique muscles. 5. During the 1000 ms after an upward saccade, constriction of the pupil consistently occurs; it apparently represents a near-triad response, for which concurrent convergence is masked. Such near-triad activation during upward gaze would presumably be necessary to counterbalance residual steady-state torques from the superior oblique muscles. 6. The up-down asymmetry of intrasaccadic vergence changes also arises when targets require both a vergence change and a vertical shift of gaze, thereby accelerating refixation for the typical natural spatial configuration, in which nearer objects are lower in the visual field. 7. During binocular viewing of equidistant targets, the convergence resulting from downward saccades produces large transient disparities, which can be expected to lead to biased evaluations of relative distances to targets. Several up-down illusions involving apparent distance may well be due to these disparities, including (a) backward tilt of the apparent vertical and of the vertical horopter, (b) the 'soup-bowl sky' illusion, and (c) the 'diverging sunbeams' illusion.