West Nile virus illness in Ontario, Canada: 2017.

BACKGROUND: In Canada, the annual incidence rates of West Nile virus (WNV) illness have fluctuated over the last 15 years. Ontario is one of the provinces in Canada most affected by WNV and, as a result, has implemented robust mosquito and human surveillance programs. OBJECTIVE: To summarize and discuss the epidemiology of WNV illness in Ontario, Canada in 2017, with comparisons to previous years. METHODS: Case data were obtained from the provincial integrated Public Health Information System. Provincial and public health unit (PHU)-specific incidence rates by year were calculated using population data extracted from intelliHEALTH Ontario. RESULTS: In 2017, the incidence of WNV illness in Ontario was 1.1 cases per 100,000 population, with 158 confirmed and probable cases reported by 27 of the province's 36 PHUs. This is the highest rate since 2013, but less than the rate in 2012 (2.0 cases per 100,000 population). Incidence rates in 2017 were highest in Windsor-Essex County and in PHUs in eastern Ontario. While the seasonality is consistent with previous years, the number of cases reported between July and September 2017 was above expected. Most cases were in older age groups (median: 58 years old) and males (59.5% of provincial total); cases with severe outcomes (neurological complications, hospitalizations, deaths) were also disproportionately in older males. CONCLUSION: WNV illness continues to be an ongoing burden in Ontario. The increase in the number of cases reported in 2017, and the increased number of PHUs reporting cases, suggests changing and expanding risk levels in Ontario. Continued mosquito and human surveillance, increased awareness of preventive measures, and early recognition and treatment are needed to mitigate the impact of WNV infections.

A descriptive analysis of rabies post-exposure prophylaxis data: 2013, Ontario, Canada.

By 2013, the number of confirmed rabid animals in Ontario had decreased to unprecedented low numbers, yet the expected decrease in the number of courses of rabies post-exposure prophylaxis (RPEP) administered did not occur consistent with the decrease in animal rabies cases (Figure ). This prompted a review of the reasons that RPEP was administered in Ontario. This study provides a descriptive analysis of the exposure incidents resulting in RPEP administration in Ontario during 2013 using data obtained from the integrated Public Health Information System, a Web-based disease surveillance system. Findings from the study revealed that the number of RPEP courses administered could be reduced, without increased risk of rabies, through the following strategies: (i) Education and resources for public health staff and healthcare providers who assess animal exposures to improve interpretation of guidelines for RPEP administration. (ii) Refinement of guidelines for public health staff and healthcare providers to ensure that they support detailed consideration of the circumstances of the exposure in order to assist with the risk assessment. Guidelines should also support completion of a risk assessment when exposures to skunks, foxes, raccoons and other wild carnivores are provoked by the victim, as opposed to automatically providing RPEP as recommended by current guidelines. (iii) Public education strategies to prevent exposures to animals (e.g., do not touch unattended animals, bat proofing your house, proper removal of bats from the house). (iv) Defining the criteria to declare a jurisdiction rabies-free. (v) Exploring strategies to improve surveillance for rabid animals.

The continued rise of Lyme disease in Ontario, Canada: 2017.

BACKGROUND: Lyme disease is an infection caused by the spirochete Borrelia burgdorferi and, in most of North America, is transmitted by the blacklegged tick Ixodes scapularis. Climate change has contributed to the expansion of the geographic range of blacklegged ticks in Ontario, increasing the risk of Lyme disease for Ontarians. OBJECTIVE: To identify the number of cases and incidence rates, as well as the geographic, seasonal and demographic distribution of Lyme disease cases reported in Ontario in 2017, with comparisons to historical trends. METHODS: Data for confirmed and probable Lyme disease cases with episode dates from January 1, 2012, through December 31, 2017, were extracted from the integrated Public Health Information System (iPHIS). Data included public health unit (PHU) of residence, episode date, age and sex. Population data from Statistics Canada were used to calculate provincial and PHU-specific incidence rates per 100,000 population. The number of cases reported in 2017 by PHU of residence, month of occurrence, age and sex was compared to the 5-year averages for the period 2012-2016. RESULTS: There were 959 probable and confirmed cases of Lyme disease reported in Ontario in 2017. This was three times higher than the 5-year (2012-2016) average of 313. The provincial incidence rate for 2017 was 6.7 cases per 100,000 population, although this varied markedly by PHU. The highest incidence rates were found in Leeds-Grenville and Lanark District (128.8 cases per 100,000), Kingston-Frontenac, Lennox and Addington (87.2 cases per 100,000), Hastings and Prince Edward Counties (28.6 cases per 100,000), Ottawa (18.1 cases per 100,000) and Eastern Ontario (13.5 cases per 100,000). Cases occurred mostly from June through September, were most common among males, and those aged 5-14 and 50-69 years. CONCLUSION: In 2017, Lyme disease incidence showed a marked increase in Ontario, especially in the eastern part of the province. If current weather and climate trends continue, blacklegged ticks carrying tick-borne pathogens, such as those causing Lyme disease, will continue to spread into suitable habitat. Monitoring the extent of this geographic spread will inform future clinical and public health actions to detect and mitigate the impact of Lyme disease in Ontario.

The roles and functions of cutaneous mechanoreceptors.

Combined psychophysical and neurophysiological research has resulted in a relatively complete picture of the neural mechanisms of tactile perception. The results support the idea that each of the four mechanoreceptive afferent systems innervating the hand serves a distinctly different perceptual function, and that tactile perception can be understood as the sum of these functions. Furthermore, the receptors in each of those systems seem to be specialized for their assigned perceptual function.

Spatial and temporal structure of receptive fields in primate somatosensory area 3b: effects of stimulus scanning direction and orientation.

This is the third in a series of studies of the neural representation of tactile spatial form in somatosensory cortical area 3b of the alert monkey. We previously studied the spatial structure of >350 fingerpad receptive fields (RFs) with random-dot patterns scanned in one direction () and at varying velocities (). Those studies showed that area 3b RFs have a wide range of spatial structures that are virtually unaffected by changes in scanning velocity. In this study, 62 area 3b neurons were studied with three to eight scanning directions (58 with four or more directions). The data from all three studies are described accurately by an RF model with three components: (1) a single, central excitatory region of short duration, (2) one or more inhibitory regions, also of short duration, that are adjacent to and nearly synchronous with the excitation, and (3) a region of inhibition that overlaps the excitation partially or totally and is temporally delayed with respect to the first two components. The mean correlation between the observed RFs and the RFs predicted by this three-component model was 0.81. The three-component RFs also predicted orientation sensitivity and preferred orientation to a scanned bar accurately. The orientation sensitivity was determined most strongly by the intensity of the coincident RF inhibition in relation to the excitation. Both orientation sensitivity and this ratio were stronger in the supragranular and infragranular layers than in layer IV.

Neural coding mechanisms underlying perceived roughness of finely textured surfaces.

Combined psychophysical and neurophysiological studies have shown that the perceived roughness of surfaces with element spacings of >1 mm is based on spatial variation in the firing rates of slowly adapting type 1 (SA1) afferents (mean absolute difference in firing rates between SA1 afferents with receptive fields separated by approximately 2 mm). The question addressed here is whether this mechanism accounts for the perceived roughness of surfaces with element spacings of <1 mm. Twenty triangular and trapezoidal gratings plus a smooth surface were used as stimulus patterns [spatial periods, 0.1-2.0 mm; groove widths (GWs), 0.1-2.0 mm; and ridge widths (RWs), 0-1.0 mm]. In the human psychophysical studies, we found that the following equation described the mean roughness magnitude estimates of the subjects accurately (0.99 correlation): 0.2 + 1.6GW - 0.5RW - 0.25GW(2). In the neurophysiological studies, these surfaces were scanned across the receptive fields of SA1, rapidly adapting, and Pacinian (PC) afferents, innervating the glabrous skin of anesthetized macaque monkeys. SA1 spatial variation was highly correlated (0.97) with human roughness judgments. There was no consistent relationship between PC responses and roughness judgments; PC afferents responded strongly and almost equally to all of the patterns. Spatial variation in SA1 firing rates is the only neural code that accounts for the perceived roughness of surfaces with finely and coarsely spaced elements. When surface elements are widely spaced, the spatial variation in firing rates is determined primarily by the surface pattern; when the elements are finely spaced, the variation in firing rates between SA1 afferents is determined by stochastic variation in spike rates.

Human Rabies Post-Exposure Prophylaxis and Animal Rabies in Ontario, Canada, 2001-2012.

In Ontario, Canada, the implementation of an annual rabies control programme in wildlife that began in 1989 resulted in a marked, steady decrease in the number of animal rabies cases. The number of animal rabies cases decreased from 1870 in 1989 to 183 in 2000 (Nunan et al., 2002 Emerg Infect Dis 8, 214). In our study period, the number of animal rabies cases continued to decrease from 210 in 2001 to 28 in 2012. The marked decrease in animal rabies cases since 1989 has resulted in a decrease in the risk of human infection. A concomitant decrease in the number of rabies post-exposure prophylaxis (RPEP) administered was anticipated but failed to occur. The mean rate of RPEP, 13.9 RPEP administered per 100,000 persons, from 2001-2012 was approximately the same as the rate in the 1990 s. Two possible reasons that the rate of RPEP administration has not decreased include strict adherence to RPEP recommendations and administration of RPEP when it is not recommended. A reduction in the number of RPEP administered, consistent with the decrease in the animal rabies cases, would provide some financial savings for the government. Ideally, an increased use of the risk assessment approach in keeping with recent guidelines, rather than adhering to previous prescriptive recommendations for RPEP administration, coupled with a continuing low incidence of animal rabies cases will result in decreased, and yet appropriate, use of RPEP. Consideration should be given to identify how guidelines could be revised to more effectively target high-risk exposures and reduce the administration of RPEP for instances in which the risk of rabies virus exposure is exceedingly low.

Differences in spatial acuity between digits.

The spatial acuity of the index, middle, and ring distal finger pads of eight right-handed men, aged 22 to 57 years, was measured by using gratings and raised letters. Acuity declined significantly from the index to the middle finger and from the middle to the ring finger. There were no significant differences between homologous fingers of the two hands. Letter recognition and grating orientation threshold measures were highly correlated.

The limit of tactile spatial resolution in humans: grating orientation discrimination at the lip, tongue, and finger.

The sensory neural pathways serving the lip, tongue, and finger are specialized for spatial information processing; thus, damage to these pathways is likely to be manifested most prominently as a loss of spatial acuity. For that reason, accurate measurement of spatial resolution at these regions is particularly important. The conventional test, the two-point discrimination task, does not measure the limit of spatial resolution and it yields variable results because it does not control nonspatial cues. The aim of this study was to quantify the limits of spatial resolution at the lip, tongue, and finger and to study the repeatability of those measurements using a stimulus that does not introduce nonspatial cues. We employed a grating orientation discrimination test, which has been studied extensively in relation to the underlying neural mechanisms. We obtained psychophysical thresholds for tactile spatial resolution from 15 normal, young adult subjects over seven test sessions. The finest gratings whose orientations were discriminated reliably had groove widths (gratings had equal groove and bar widths) that averaged 0.51 mm at the lip, 0.58 mm at the tongue, and 0.94 mm at the finger. These threshold measurements were highly reproducible between sessions with an overall improvement of 2% per session. These data suggest that the grating orientation discrimination task provides a stable, reliable measure of the human capacity for spatial resolution.

A rotating drum stimulator for scanning embossed patterns and textures across the skin.

A tactile stimulator is described that moves embossed or textured patterns tangentially across the skin. Patterns constructed by standard photoetching are mounted on the outer surface of a cylinder that rotates at a selected speed and is held in contact with the skin at a selected force. The stimulator operates in several modes to meet the different requirements of psychophysical and neurophysiological experiments. The features of note are (i) relatively small size and weight; (ii) flexible automated control of drum contact with the skin, angular velocity, axial position, and contact force; (iii) monitoring of drum angular and axial location to better than 10 micron accuracy; (iv) construction with commercially available devices; (v) electronic monitoring of skin contact; and (vi) rapid drum changes (2 seconds) during psychophysical or neurophysiological experiments.

Marking microelectrode penetrations with fluorescent dyes.

Fluorescent dyes were used to mark and identify the tracks left by extracellular microelectrodes in neurophysiological experiments. Forty-two penetrations were made into the postcentral gyrus of 3 Macaque monkeys with electrodes coated with 1 of 5 fluorescent dyes (DiI, DiO, DiI-C5, PyPO, and Fast Blue). The electrodes were driven at rates ranging from 10 to 1000 microns/min, to a depth of about 4000 microns, where a small electrolytic lesion was made. Histological sections were viewed under fluorescent optics and the electrode tracks were reconstructed from the dye traces. Fluorescent traces (width 50-400 microns) were observed in 41 of 42 penetrations with 24 traces extending to the lesion site. Of the electrodes driven in less than 3 h, those coated with DiI (8/8) and DiI-C5 (8/8) left a trace to the lesion site, while 57% (4/7) of the DiO, 40% (2/5) of the Fast Blue and only 11% (1/9) of the PyPO tracks were fully marked. This method of marking penetrations can be used with any extracellular recording configuration, does not require tissue sections to be processed or stained, does not require electrical lesions, and causes no detectable tissue damage. Because the dyes fluoresce at different wavelengths, closely spaced tracks can be uniquely identified.

Tactile functions of mechanoreceptive afferents innervating the hand.

Four types of mechanoreceptive afferents innervate the glabrous skin of the hand. Evidence from more than three decades of combined psychophysical and neurophysiological research supports the idea that each afferent type serves a distinctly different sensory function and that these functions explain most of tactual perceptual function. The available evidence supports the following hypotheses: (1) The slowly adapting type 1 system provides the information on which form and texture perception are based. (2) The cutaneous rapidly adapting system provides information about minute skin motion and, thereby, plays a critical role in grip control. (3) The Pacinian system is responsible for the detection and perception of distant events by vibrations transmitted through objects, probes, and tools held in the hand. (4) The slowly adapting type 2 system provides information for the perception of hand conformation and for the perception of forces acting on the hand. The authors review the evidence on which these hypotheses are based. They also review the role of proprioceptive afferents in the perception of hand conformation because they appear to play a significant role along with cutaneous afferents.

The utilization of trifluorothymidine (TFT) to select for thymidine kinase-deficient (TK-/-) mutants from L5178Y/TK+/- mouse lymphoma cells.

Trifluorothymidine (TFT), a thymidine analog, was analyzed for its ability to select for thymidine kinase-deficient (TK-/-) mutants. In comparison with BUdR, the traditional selective agent for TK-/- cells, it was determined that TFT at 1/50th the dose (1 microgram/ml vs. 50 microgram/ml) is a more effective and versatile selective agent for TK-/- mutants arising from the TK+/- -3.7.2C heterozygote of L5178Y mouse lymphoma cells. Since TFT acts more rapidly than BUdR, it can be utilized in procedures (such as the analysis of the phenotypic lag) requiring the fast arrest of cell division. Reconstruction analyses of effective TK-/- mutant recovery indicate that TFT can be used to recover mutants from significantly higher densities of TK+/- cells than can BUdR. In addition, TK-/- mutants can attain larger colony size in TFT than in BudR where severe stunting of growth occurs at high TK-/- cell densities. 190 of 194 isolated TFT-resistant large and small colony mutants (both spontaneous and induced).

Validation and characterization of the L5178Y/TK+/- mouse lymphoma mutagen assay system.

The current status of the L5178Y/TK+/- leads to TK-/- mouse-lymphoma mutagenicity assay is described. Dose-survival-mutagenic response data are shown for 43 chemicals. Mutagenicity and cytotoxicity in the presence or absence of non-induced and/or Aroclor-induced rat-liver S-9 are compared for most of these chemicals, 25 of these for which usuable carcinogenicity data exist have been used to construct an approximately linear relationship between oncogenic potency in vivo and mutagenic potency in this system in vitro; linearity between these two endpoints extends over a greater than 100,000-fold range in potencies. Several carcinogens which are negative or difficult to detect in the standard Ames assay are mutagenic in this mammalian cell system. These include natulan, sodium saccharin (lot S-1022), p,p'-DDE (metabolite of DDT), dimethylnitrosamine, diethylnitrosamine and diethylstilbestrol. Characterization of the TK-/- mutants suggests that two mutagenic mechanisms contribute to their final yield. Large-colony TK-/- mutants probably represent point or gene mutations affecting the TK locus. In addition, a class of small-colony TK(/- mutants are described and characterized as being heritably growth-deficient; this and other properties suggest that these small-colony TK-/- mutants originate by a heritable and viable chromosomal aberration. Most carcinogens and mutagens tested produce both classes of TK-/- mutants in this system; the relative proportions of small- and large-colony mutants are both mutagen- and dose-dependent. Comparative studies have been done at the rapidly-expressing TK locus and the slowly-expressing HGPRT locus in these cells. Several carcinogens detected at the TK locus are non- or very weakly mutagenic at the HGPRT locus. This findings is consistent with the induction of slow-growing specific locus mutants by a chromosomal mechanism and their subsequent dilution during this long expression time.

Optimal detection, classification, and superposition resolution in neural waveform recordings.

The effects of noise autocorrelation on neural waveform recognition (detection, classification, and superposition resolution) are investigated in this study using microelectrode recordings from the cortex of a monkey. Optimal waveform recognition is accomplished by passing the data through a whitening filter before matched filtering for detection or template matching for classification and superposition resolution. Template matching without whitening requires about 40% higher signal-to-noise ratio than template matching with whitening for comparable classification and superposition resolution. The comparable difference for detection is 15%.

Roughness coding in the somatosensory system.

Roughness perception is coded in the somatosensory system by neurons in the type I slowly adapting (SAI) system. When the fingers scan a surface, an isomorphic representation of the surface is encoded in the discharge patterns of SAI afferents. Central neurons in area 3b of primary somatosensory (SI) cortex spatially filter the peripheral image to compute local spatial variation. The outputs from these neurons converge onto neurons in area 1 and onto neurons in secondary somatosensory (SII) cortex which we believe is the critical processing pathway underlying roughness perception.

Perspectives on the role of afferent signals in control of motor neuroprostheses.

K.O. Johnson reviews the architecture and low level neural mechanisms by which the external environment is transduced and encoded into the neural system, summarizing work that correlates neurophysiological and psychophysical testing with isolation of sensory components. The slowly adapting Type I afferent system is responsible for form and texture perception; the rapidly adapting afferent system is responsible for motion perception; and the Pacinian corpuscle system is responsible for vibratory sensation. R.R. Riso reviews the current level of understanding of the major factors to be considered in the design of a functional neuromuscular stimulation (FNS) grasp controller that uses cutaneous sensory feedback to detect slip. The elegant natural control scheme that matches the ratio of grip and lift forces to frictional conditions provides a model for implementing a slip-based control algorithm. D. Popovic discusses the possible use of recordings from more proximal peripheral nerves to determine needed information for synthesis of locomotion. The discussion is illustrated with an animal model where rule-based closed-loop control is used for the ankle joint during treadmill locomotion. Neural signals from the tibial and superficial peroneal nerves were employed to substitute for missing afferent input from cutaneous and proprioceptive sensors. The feasibility of more invasive intraneural electrodes for distinguishing sensory from motor information in mixed nerves is considered. M. Koris raises surgical and functional issues relevant to developing clinical FNS systems. C. Van Doren suggests alternative neurophysiological and engineering approaches.