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.

Temporal precision in circadian systems: a reliable neuronal clock from unreliable components?

Mutual coupling among oscillators of an ensemble has been proposed to explain the precision of some circadian rhythms. Reciprocal triggering is one of the most familiar forms of mutual coupling in nervous systems, but it can at best produce only modest improvement in temporal precision. Nevertheless, models with an elementary elaboration of such coupling show that circadian precision could be derived from oscillators that are intrinsically "sloppy"; sufficient conditions are that output of the individual components be summed and that mutual triggering be mediated by a nonlinear phenomenon, such as a threshold.

Temperature compensation in short-duration time-measurement by an intertidal amphipod.

The duration of the swimming response of an intertidal amphipod to increases in hydrostatic pressure apparently serves to measure the timing of wave uprush on the beach. Experiments have demonstrated that this response to a standard pressure-increase stimulus varies in duration only slightly with temperature over the range from 10 degrees to 28 degrees C, with estimated Q(10) values of 1.3 to 1.5. Relative insensitivity to temperature, such as here described, seems to be an essential component of biological time-measuring systems (including endogenous circadian, tidal, and lunar rhythms) that are ecologically keyed to the timing of temperature-independent environmental factors.

Distortions of apparent velocity: a new optical illusion.

To an observer whose one eye is covered with a relatively strong filter (approximately 90 percent extinction) and who views a landscape from the side window of a moving automobile, the velocity of the vehicle appears to be markedly reduced when the uncovered eye is in the forward or leading position (in the sense of motion of the vehicle); the velocity seems to be increased when the covered eye is in the leading position. The illusion of reduced velocity is accompanied by an apparent dwarfing of objects near the roadside and an apparent foreshortening of the distance between object and observer; the illusion of increased velocity is accompanied by an apparent increase in size of objects and an increase in their apparent distance. These illusions can be understood as corollaries of the well-known Pulfrich phenomenon.

Vertical diurnal migration and endogenous rhythmicity.

Experimental studies of mixed populations of marine zooplankton have demonstrated that internal rhythms, synchronized by a light-dark cycle, are of dominant importance for the vertical migration of several species of crustaceans. For certain other organisms, the vertical migrations observed in the experiments can be accounted for as direct responses to light intensity only. Performances intermediate between these extremes were also observed, as well as behavior based on biological timing mechanisms that are not rhythms in the usual sense.

Long-term activity recording in small aquatic animals.

We have built an activity-recording device based on the principle of detecting slight changes in the heat conductance of an aquatic environment by means of a thermistor. A major advantage of the device is that it can be used with a simple event recorder, thus combining high sensitivity with low cost. The equipment has been tested with automatic mechanical stimulation, and has been used for long-term recording of the swimming of small marine crustaceans. Problems of stability and reliability have been solved, and potential applications of the device seem widespread.

The parallactic view, statistical testing, and circular reasoning.

A "parallactic view" (i.e., subjectivity in interpreting data) is an important and perhaps essential tool for formulating hypotheses, but it also represents a hazardous contaminant to be avoided in testing hypotheses. Computer simulations demonstrate that statistical testing of data that are contaminated by even a modest level of such parallax can be very misleading; probability levels are greatly distorted. An even more insidious influence of the parallactic view arises when the fundamental assumptions for a statistical test are not adequately respected. Single-cosinor analysis, which has been used to "demonstrate" circaseptan rhythms (tau = about 7 days), lends itself to such abuse: The statistical test of the zero-amplitude hypothesis assumes that if any serial correlation is present in the data, it is due to a sinusoidal oscillation with period that is known a priori. One cannot, therefore, legitimately use this method to demonstrate the existence of such a rhythm.

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.

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.

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.

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.

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.

The aftermath of horizontal saccades: saccadic retraction and cyclotorsion.

During horizontal saccades from either nasal or temporal direction, the eye is retracted into its orbit (about 100 micron for 8 degrees saccades), presumably due to co-contraction of the recti. That translational displacement of the eye thereafter slowly decays, with a half-time of about 100 msec. Transient cyclotorsion (up to 1 degree) also often arises during a saccade, with a direction of movement which depends upon pre-saccade position of the eye. When present, it decays with a half-time of about a full second, frequently leaving residual torsion, the direction of which also depends on where the saccade originated (static hysteresis). These two sorts of slow recovery process greatly extend the "duration" of a saccade, compared with presently accepted values.

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.

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.

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].

Perspective vergence: oculomotor responses to line drawings.

When a perspective drawing is viewed monocularly, changes in fixation point are accompanied by changes in steady-state vergence; their direction is usually appropriate for the distance relationships implied in the illustration. The absolute magnitude of these responses varies appreciably among subjects; it can be consistently enhanced or reduced by modest changes in the drawing. Similar configurations of stimuli from three-dimensional objects would presumably also contribute to normal vergence movements during binocular viewing; it appears that their importance would increase with target distance. Corresponding changes in pupil diameter, as expected for the "near reflex", were not observed with perspective stimuli. Consistent, directionally appropriate vergence changes, paralleling perception, were also made by most subjects during monocular viewing of a Necker cube, but there, exceptionally large pupillary responses arose.