Treating sensitive cervical areas with ozone. A prospective controlled clinical trial

PURPOSE: To determine whether the treatment of hypersensitive teeth with gaseous ozone (Healozone, KaVo 1600 ppm) for 60 seconds reduces pain immediately after treatment and in the longer term. METHODS: In three private practices in Switzerland, 31 subjects suffering from hypersensitive teeth were treated with gaseous ozone over a period of 54 weeks (one test and one control tooth in each subject). A cross-over design was chosen. The pain level was measured with a Visual Analogue Scale before and after the treatment. RESULTS: The subjects' pain level was reduced by 55% +/- 5.5% immediately after the ozone treatment. Over time, the pain level decreased significantly in all groups: The pain level in the test teeth was significantly reduced in Weeks 0-22 (treatment group, P < 0.001) compared to the pain level before treatment. The pain level in the control group was also reduced significantly over time in Weeks 0-22 (no-treatment, P = 0.025) and in Weeks 22-54 (treatment group, P = 0.0065). Comparing test and control teeth over time, there was no statistically significant difference in pain reduction (P = 0.58).

Assessing visual disturbance conditions on the Custer National Forest

Assessment of soil disturbance on the Custer National Forest was conducted during two summers to determine if the U.S. Forest Service Forest Soil Disturbance Monitoring Protocol (FSDMP) was able to distinguish post-harvest soil conditions in a chronological sequence of sites harvested using different ground-based logging systems. Results from the first year of sampling suggested that the FSDMP point sampling method may not be sensitive enough to measure post-harvest disturbance in stands with low levels of disturbance. Therefore, a revised random transect method was used during the second sampling season to determine the actual extent of soil disturbance in these cutting units. Using combined data collected from both summers I detected statistically significant differences (p < 0.05) in fine fraction bulk density measurements between FSDMP disturbance classes across all sites. Disturbance class 3 (most severe) had the highest reported bulk density, which suggest that the FSDMP visual class estimates are defined adequately allowing for correlations to be made between visual disturbance and actual soil physical characteristics. Forest site productivity can be defined by its ability to retain carbon and convert it to above- and belowground biomass. However, forest management activities that alter basic site characteristics have the potential to alter productivity. Soil compaction is one critical management impact that is important to understand; compaction has been shown to impede the root growth potential of plants, reduce water infiltration rates increasing erosion potential, and alter plant available water and nutrients, depending on soil texture. A new method to assess ground cover, erosion, and other soil disturbances was recently published by the U.S. Forest Service, as the Forest Soil Disturbance Protocol (FSDMP). The FSDMP allows soil scientists to visually assign a disturbance class estimate (0 – none, 1, 2, 3 – severe) from field measures of consistently defined soil disturbance indicators (erosion, fire, rutting, compaction, and platy/massive/puddled structure) in small circular (15 cm) plots to compare soil quality properties pre- and post- harvest condition. Using this protocol we were able to determine that ground-based timber harvesting activities occurring on the Custer National Forest are not reaching the 15% maximum threshold for detrimental soil disturbance outlined by the Region 1 Soil Quality Standards.

Recovery of visual field and acuity after removal of epiretinal and inner limiting membranes

BACKGROUND: Visual acuity serves as only a rough gauge of macular function. The aim therefore was to ascertain whether central an assessment of the central visual field afforded a closer insight into visual function after removal of epiretinal membranes and Infracyanine-Green- or Trypan-Blue-assisted peeling of the inner limiting membrane. Patients and methods: Fourty-three patients undergoing pars-plana vitrectomy for the removal of epimacular membranes and dye-assisted peeling of the inner limiting membrane using either Infracyanine Green (n = 29; group 1) or Trypan Blue (n = 14; group 2) were monitored prospectively for 12 months. Preoperatively, and 1, 6 and 12 months postoperatively, distance and reading visual acuities were evaluated; the central visual field was assessed by automated static perimetry. RESULTS: Twelve months after surgery, distance and reading visual acuities had improved in both groups, but to a significant degree only in Trypan-Blue-treated eyes. The difference between the two groups was not significant. Likewise at this juncture, the mean size of the visual-field defect remained unchanged in Trypan-Blue-treated eyes (preoperative: 4.3 (SD 2.1) dB; 12 months: 4.0 (2.1) dB (p = 0.15)), but had increased in Infracyanine-Green-treated ones (from 5.3 (3.7) dB to 8.0 (5.2) dB (p = 0.027)). CONCLUSION: Unlike visual acuity, the central visual field had deteriorated in Infracyanine-Green-treated eyes but not in Trypan-Blue-treated eyes 12 months after surgery. Hence, as a predictor of functional outcome, testing of the central visual field may be a more sensitive gauge than visual acuity. Furthermore, Infracyanine Green may have a chronic and potentially clinically relevant effect on the macula which is not reflected in the visual acuity.

Spring temperature variability and eutrophication history inferred from sedimentary pigments in the varved sediments of Lake Żabińskie, north-eastern Poland, AD 1907–2008

Varved lake sediments are excellent natural archives providing quantitative insights into climatic and environmental changes at very high resolution and chronological accuracy. However, due to the multitude of responses within lake ecosystems it is often difficult to understand how climate variability interacts with other environmental pressures such as eutrophication, and to attribute observed changes to specific causes. This is particularly challenging during the past 100 years when multiple strong trends are superposed. Here we present a high-resolution multi-proxy record of sedimentary pigments and other biogeochemical data from the varved sediments of Lake Żabińskie (Masurian Lake District, north-eastern Poland, 54°N–22°E, 120 m a.s.l.) spanning AD 1907 to 2008. Lake Żabińskie exhibits biogeochemical varves with highly organic late summer and winter layers separated by white layers of endogenous calcite precipitated in early summer. The aim of our study is to investigate whether climate-driven changes and anthropogenic changes can be separated in a multi-proxy sediment data set, and to explore which sediment proxies are potentially suitable for long quantitative climate reconstructions. We also test if convoluted analytical techniques (e.g. HPLC) can be substituted by rapid scanning techniques (visible reflectance spectroscopy VIS-RS; 380–730 nm). We used principal component analysis and cluster analysis to show that the recent eutrophication of Lake Żabińskie can be discriminated from climate-driven changes for the period AD 1907–2008. The eutrophication signal (PC1 = 46.4%; TOC, TN, TS, Phe-b, high TC/CD ratios total carotenoids/chlorophyll-a derivatives) is mainly expressed as increasing aquatic primary production, increasing hypolimnetic anoxia and a change in the algal community from green algae to blue-green algae. The proxies diagnostic for eutrophication show a smooth positive trend between 1907 and ca 1980 followed by a very rapid increase from ca. 1980 ± 2 onwards. We demonstrate that PC2 (24.4%, Chl-a-related pigments) is not affected by the eutrophication signal, but instead is sensitive to spring (MAM) temperature (r = 0.63, pcorr < 0.05, RMSEP = 0.56 °C; 5-yr filtered). Limnological monitoring data (2011–2013) support this finding. We also demonstrate that scanning visible reflectance spectroscopy (VIS-RS) data can be calibrated to HPLC-measured chloropigment data and be used to infer concentrations of sedimentary Chl-a derivatives {pheophytin a + pyropheophytin a}. This offers the possibility for very high-resolution (multi)millennial-long paleoenvironmental reconstructions.

Image analysis of immunohistochemistry is superior to visual scoring as shown for patient outcome of esophageal adenocarcinoma.

Quantification of protein expression based on immunohistochemistry (IHC) is an important step in clinical diagnoses and translational tissue-based research. Manual scoring systems are used in order to evaluate protein expression based on staining intensities and distribution patterns. However, visual scoring remains an inherently subjective approach. The aim of our study was to explore whether digital image analysis proves to be an alternative or even superior tool to quantify expression of membrane-bound proteins. We analyzed five membrane-binding biomarkers (HER2, EGFR, pEGFR, β-catenin, and E-cadherin) and performed IHC on tumor tissue microarrays from 153 esophageal adenocarcinomas patients from a single center study. The tissue cores were scored visually applying an established routine scoring system as well as by using digital image analysis obtaining a continuous spectrum of average staining intensity. Subsequently, we compared both assessments by survival analysis as an end point. There were no significant correlations with patient survival using visual scoring of β-catenin, E-cadherin, pEGFR, or HER2. In contrast, the results for digital image analysis approach indicated that there were significant associations with disease-free survival for β-catenin, E-cadherin, pEGFR, and HER2 (P = 0.0125, P = 0.0014, P = 0.0299, and P = 0.0096, respectively). For EGFR, there was a greater association with patient survival when digital image analysis was used compared to when visual scoring was (visual: P = 0.0045, image analysis: P < 0.0001). The results of this study indicated that digital image analysis was superior to visual scoring. Digital image analysis is more sensitive and, therefore, better able to detect biological differences within the tissues with greater accuracy. This increased sensitivity improves the quality of quantification.

Dynamic gamma frequency feedback coupling between higher and lower order visual cortices underlies perceptual completion in humans

To perceive a coherent environment, incomplete or overlapping visual forms must be integrated into meaningful coherent percepts, a process referred to as ?Gestalt? formation or perceptual completion. Increasing evidence suggests that this process engages oscillatory neuronal activity in a distributed neuronal assembly. A separate line of evidence suggests that Gestalt formation requires top-down feedback from higher order brain regions to early visual cortex. Here we combine magnetoencephalography (MEG) and effective connectivity analysis in the frequency domain to specifically address the effective coupling between sources of oscillatory brain activity during Gestalt formation. We demonstrate that perceptual completion of two-tone ?Mooney? faces induces increased gamma frequency band power (55?71 Hz) in human early visual, fusiform and parietal cortices. Within this distributed neuronal assembly fusiform and parietal gamma oscillators are coupled by forward and backward connectivity during Mooney face perception, indicating reciprocal influences of gamma activity between these higher order visual brain regions. Critically, gamma band oscillations in early visual cortex are modulated by top-down feedback connectivity from both fusiform and parietal cortices. Thus, we provide a mechanistic account of Gestalt perception in which gamma oscillations in feature sensitive and spatial attention-relevant brain regions reciprocally drive one another and convey global stimulus aspects to local processing units at low levels of the sensory hierarchy by top-down feedback. Our data therefore support the notion of inverse hierarchical processing within the visual system underlying awareness of coherent percepts.

Neuronal coincidence detection by voltage-sensitive electrical synapses

Coincidence detection is important for functions as diverse as Hebbian learning, binaural localization, and visual attention. We show here that extremely precise coincidence detection is a natural consequence of the normal function of rectifying electrical synapses. Such synapses open to bidirectional current flow when presynaptic cells depolarize relative to their postsynaptic targets and remain open until well after completion of presynaptic spikes. When multiple input neurons fire simultaneously, the synaptic currents sum effectively and produce a large excitatory postsynaptic potential. However, when some inputs are delayed relative to the rest, their contributions are reduced because the early excitatory postsynaptic potential retards the opening of additional voltage-sensitive synapses, and the late synaptic currents are shunted by already opened junctions. These mechanisms account for the ability of the lateral giant neurons of crayfish to sum synchronous inputs, but not inputs separated by only 100 μsec. This coincidence detection enables crayfish to produce reflex escape responses only to very abrupt mechanical stimuli. In light of recent evidence that electrical synapses are common in the mammalian central nervous system, the mechanisms of coincidence detection described here may be widely used in many systems.

Visual stimuli induce waves of electrical activity in turtle cortex

The computations involved in the processing of a visual scene invariably involve the interactions among neurons throughout all of visual cortex. One hypothesis is that the timing of neuronal activity, as well as the amplitude of activity, provides a means to encode features of objects. The experimental data from studies on cat [Gray, C. M., Konig, P., Engel, A. K. & Singer, W. (1989) Nature (London) 338, 334–337] support a view in which only synchronous (no phase lags) activity carries information about the visual scene. In contrast, theoretical studies suggest, on the one hand, the utility of multiple phases within a population of neurons as a means to encode independent visual features and, on the other hand, the likely existence of timing differences solely on the basis of network dynamics. Here we use widefield imaging in conjunction with voltage-sensitive dyes to record electrical activity from the virtually intact, unanesthetized turtle brain. Our data consist of single-trial measurements. We analyze our data in the frequency domain to isolate coherent events that lie in different frequency bands. Low frequency oscillations (<5 Hz) are seen in both ongoing activity and activity induced by visual stimuli. These oscillations propagate parallel to the afferent input. Higher frequency activity, with spectral peaks near 10 and 20 Hz, is seen solely in response to stimulation. This activity consists of plane waves and spiral-like waves, as well as more complex patterns. The plane waves have an average phase gradient of ≈π/2 radians/mm and propagate orthogonally to the low frequency waves. Our results show that large-scale differences in neuronal timing are present and persistent during visual processing.

Avoidance of obstacles in the absence of visual awareness

The spatial character of our reaching movements is extremely sensitive to potential obstacles in the workspace. We recently found that this sensitivity was retained by most patients with left visual neglect when reaching between two objects, despite the fact that they tended to ignore the leftward object when asked to bisect the space between them. This raises the possibility that obstacle avoidance does not require a conscious awareness of the obstacle avoided. We have now tested this hypothesis in a patient with visual extinction following right temporoparietal damage. Extinction is an attentional disorder in which patients fail to report stimuli on the side of space opposite a brain lesion under conditions of bilateral stimulation. Our patient avoided obstacles during reaching, to exactly the same degree, regardless of whether he was able to report their presence. This implicit processing of object location, which may depend on spared superior parietal-lobe pathways, demonstrates that conscious awareness is not necessary for normal obstacle avoidance.

Visual feedback alters the variations in corticospinal excitability that arise from rhythmic movements of the opposite limb

Augmented visual feedback can have a profound bearing on the stability of bimanual coordination. Indeed, this has been used to render tractable the study of patterns of coordination that cannot otherwise be produced in a stable fashion. In previous investigations (Carson et al. 1999), we have shown that rhythmic movements, brought about by the contraction of muscles on one side of the body, lead to phase-locked changes in the excitability of homologous motor pathways of the opposite limb. The present study was conducted to assess whether these changes are influenced by the presence of visual feedback of the moving limb. Eight participants performed rhythmic flexion-extension movements of the left wrist to the beat of a metronome (1.5 Hz). In 50% of trials, visual feedback of wrist displacement was provided in relation to a target amplitude, defined by the mean movement amplitude generated during the immediately preceding no feedback trial. Motor potentials (MEPs) were evoked in the quiescent muscles of the right limb by magnetic stimulation of the left motor cortex. Consistent with our previous observations, MEP amplitudes were modulated during the movement cycle of the opposite limb. The extent of this modulation was, however, smaller in the presence of visual feedback of the moving limb (FCR omega(2) =0.41; ECR omega(2)=0.29) than in trials in which there was no visual feedback (FCR omega(2)=0.51; ECR omega(2)=0.48). In addition, the relationship between the level of FCR activation and the excitability of the homologous corticospinal pathway of the opposite limb was sensitive to the vision condition; the degree of correlation between the two variables was larger when there was no visual feedback of the moving limb. The results of the present study support the view that increases in the stability of bimanual coordination brought about by augmented feedback may be mediated by changes in the crossed modulation of excitability in homologous motor pathways.

Induced visual illusions and gamma oscillations in human primary visual cortex

Using magnetoencephalography, we studied the spatiotemporal properties of cortical responses in terms of event-related synchronization and event-related desynchronization to a range of stripe patterns in subjects with no neurological disorders. These stripes are known for their tendency to induce a range of abnormal sensations, such as illusions, nausea, dizziness, headache and attacks of pattern-sensitive epilepsy. The optimal stimulus must have specific physical properties, and maximum abnormalities occur at specific spatial frequency and contrast. Despite individual differences in the severity of discomfort experienced, psychophysical studies have shown that most observers experience some degree of visual anomaly on viewing such patterns. In a separate experiment, subjects reported the incidence of illusions and discomfort to each pattern. We found maximal cortical power in the gamma range (30-60 Hz) confined to the region of the primary visual cortex in response to patterns of 2-4 cycles per degree, peaking at 3 cycles per degree. This coincides with the peak of mean illusions and discomfort, also maximal for patterns of 2-4 cycles per degree. We show that gamma band activity in V1 is a narrow band function of spatial frequency. We hypothesize that the intrinsic properties of gamma oscillations may underlie visual discomfort and play a role in the onset of seizures.

Colour and luminance interactions in the visual perception of motion

We sought to determine the extent to which red–green, colour–opponent mechanisms in the human visual system play a role in the perception of drifting luminance–modulated targets. Contrast sensitivity for the directional discrimination of drifting luminance–modulated (yellow–black) test sinusoids was measured following adaptation to isoluminant red–green sinusoids drifting in either the same or opposite direction. When the test and adapt stimuli drifted in the same direction, large sensitivity losses were evident at all test temporal frequencies employed (1–16 Hz). The magnitude of the loss was independent of temporal frequency. When adapt and test stimuli drifted in opposing directions, large sensitivity losses were evident at lower temporal frequencies (1–4 Hz) and declined with increasing temporal frequency. Control studies showed that this temporal–frequency–dependent effect could not reflect the activity of achromatic units. Our results provide evidence that chromatic mechanisms contribute to the perception of luminance–modulated motion targets drifting at speeds of up to at least 32°s-1. We argue that such mechanisms most probably lie within a parvocellular–dominated cortical visual pathway, sensitive to both chromatic and luminance modulation, but only weakly selective for the direction of stimulus motion.

Are poor mathematics skills associated with visual deficits in temporal processing?

Developmental learning disabilities such as dyslexia and dyscalculia have a high rate of co-occurrence in pediatric populations, suggesting that they share underlying cognitive and neurophysiological mechanisms. Dyslexia and other developmental disorders with a strong heritable component have been associated with reduced sensitivity to coherent motion stimuli, an index of visual temporal processing on a millisecond time-scale. Here we examined whether deficits in sensitivity to visual motion are evident in children who have poor mathematics skills relative to other children of the same age. We obtained psychophysical thresholds for visual coherent motion and a control task from two groups of children who differed in their performance on a test of mathematics achievement. Children with math skills in the lowest 10% in their cohort were less sensitive than age-matched controls to coherent motion, but they had statistically equivalent thresholds to controls on a coherent form control measure. Children with mathematics difficulties therefore tend to present a similar pattern of visual processing deficit to those that have been reported previously in other developmental disorders. We speculate that reduced sensitivity to temporally defined stimuli such as coherent motion represents a common processing deficit apparent across a range of commonly co-occurring developmental disorders.

Identification of visual field progression

The study developed statistical techniques to evaluate visual field progression for use with the Humphrey Field Analyzer (HFA). The long-term fluctuation (LF) was evaluated in stable glaucoma. The magnitude of both LF components showed little relationship with MD, CPSD and SF. An algorithm was proposed for determining the clinical necessity for a confirmatory follow-up examination. The between-examination variability was determined for the HFA Standard and FASTPAC algorithms in glaucoma. FASTPAC exhibited greater between-examination variability than the Standard algorithm across the range of sensitivities and with increasing eccentricity. The difference in variability between the algorithms had minimal clinical significance. The effect of repositioning the baseline in the Glaucoma Change Probability Analysis (GCPA) was evaluated. The global baseline of the GCPA limited the detection of progressive change at a single stimulus location. A new technique, pointwise univariate linear regressions (ULR), of absolute sensitivity and, of pattern deviation, against time to follow-up was developed. In each case, pointwise ULR was more sensitive to localised progressive changes in sensitivity than ULR of MD, alone. Small changes in sensitivity were more readily determined by the pointwise ULR than by the GCPA. A comparison between the outcome of pointwise ULR for all fields and for the last six fields manifested linear and curvilinear declines in the absolute sensitivity and the pattern deviation. A method for delineating progressive loss in glaucoma, based upon the error in the forecasted sensitivity of a multivariate model, was developed. Multivariate forecasting exhibited little agreement with GCPA in glaucoma but showed promise for monitoring visual field progression in OHT patients. The recovery of sensitivity in optic neuritis over time was modelled with a Cumulative Gaussian function. The rate and level of recovery was greater in the peripheral than the central field. Probability models to forecast the field of recovery were proposed.

The development of calibration and adaptive filtering procedures for neuromagnetic studies of human visual function

This thesis first considers the calibration and signal processing requirements of a neuromagnetometer for the measurement of human visual function. Gradiometer calibration using straight wire grids is examined and optimal grid configurations determined, given realistic constructional tolerances. Simulations show that for gradiometer balance of 1:104 and wire spacing error of 0.25mm the achievable calibration accuracy of gain is 0.3%, of position is 0.3mm and of orientation is 0.6°. Practical results with a 19-channel 2nd-order gradiometer based system exceed this performance. The real-time application of adaptive reference noise cancellation filtering to running-average evoked response data is examined. In the steady state, the filter can be assumed to be driven by a non-stationary step input arising at epoch boundaries. Based on empirical measures of this driving step an optimal progression for the filter time constant is proposed which improves upon fixed time constant filter performance. The incorporation of the time-derivatives of the reference channels was found to improve the performance of the adaptive filtering algorithm by 15-20% for unaveraged data, falling to 5% with averaging. The thesis concludes with a neuromagnetic investigation of evoked cortical responses to chromatic and luminance grating stimuli. The global magnetic field power of evoked responses to the onset of sinusoidal gratings was shown to have distinct chromatic and luminance sensitive components. Analysis of the results, using a single equivalent current dipole model, shows that these components arise from activity within two distinct cortical locations. Co-registration of the resulting current source localisations with MRI shows a chromatically responsive area lying along the midline within the calcarine fissure, possibly extending onto the lingual and cuneal gyri. It is postulated that this area is the human homologue of the primate cortical area V4.