Optimizing measurement of subjective amplitude of accommodation with defocus curves

PURPOSE: To determine whether letter sequences and/or lens-presentation order should be randomized when measuring defocus curves and to assess the most appropriate criterion for calculating the subjective amplitude of accommodation (AoA) from defocus curves. SETTING: Eye Clinic, School of Life & Health Sciences, Aston University, Birmingham, United Kingdom. METHODS: Defocus curves (from +3.00 diopters [D] to -3.00 D in 0.50 D steps) for 6 possible combinations of randomized or nonrandomized letter sequences and/or lens-presentation order were measured in a random order in 20 presbyopic subjects. Subjective AoA was calculated from the defocus curves by curve fitting using various published criteria, and each was correlated to subjective push-up AoA. Objective AoA was measured for comparison of blur tolerance and pupil size. RESULTS: Randomization of lens-presentation order and/or letter sequences, or lack of, did not affect the measured defocus curves (P>.05, analysis of variance). The range of defocus that maintains highest achievable visual acuity (allowing for variability of repeated measurement) was better correlated to (r = 0.84) and agreed best with ( 0.50 D) subjective push-up AoA than any other relative or absolute acuity criterion used in previous studies. CONCLUSIONS: Nonrandomized letters and lens presentation on their own did not affect subjective AoA measured by defocus curves, although their combination should be avoided. Quantification of subjective AoA from defocus curves should be standardized to the range of defocus that maintains the best achievable visual acuity.

Initiation and progression of ossification of the posterior longitudinal ligament of the cervical spine in the hereditary spinal hyperostotic mouse (twy/twy)

Ossification of the posterior longitudinal ligament (OPLL) is a significantly critical pathology that can eventually cause serious myelopathy. Ossification commences in the vertebral posterior longitudinal ligaments, and intensifies and spreads with the progression of the disease, resulting in osseous projections and compression of the spinal cord. However, the paucity of histological studies the underlying mechanisms of calcification and ossification processes remain obscure. The pathological process could be simulated in the ossifying process of the ligament in mutant spinal hyperostotic mouse (twy/twy). The aim of this study is to observe that enlargement of the nucleus pulposus followed by herniation, disruption and regenerative proliferation of annulus fibrosus cartilaginous tissues participated in the initiation of ossification of the posterior longitudinal ligament of twy/twy mice.

Multifocal intraocular lens differentiation using defocus curves

Purpose: To determine the most appropriate analysis technique for the differentiation of multifocal intraocular lens (MIOL) designs using defocus curve assessment of visual capability.Methods:Four groups of fifteen subjects were implanted bilaterally with either monofocal intraocular lenses, refractive MIOLs, diffractive MIOLs, or a combination of refractive and diffractive MIOLs. Defocus curves between -5.0D and +1.5D were evaluated using an absolute and relative depth-of-focus method, the direct comparison method and a new 'Area-of-focus' metric. The results were correlated with a subjective perception of near and intermediate vision. Results:Neither depth-of-focus method of analysis were sensitive enough to differentiate between MIOL groups (p>0.05). The direct comparison method indicated that the refractive MIOL group performed better at +1.00, -1.00 and -1.50 D and worse at -3.00, -3.50, -4.00 and -5.00D compared to the diffractive MIOL group (p

Apoptosis of neurons and oligodendrocytes in the spinal cord of spinal hyperostotic mouse (twy/twy):possible pathomechanism of human cervical compressive myelopathy

Cervical compressive myelopathy is the most serious complication of cervical spondylosis or ossification of the posterior longitudinal ligament (OPLL) and the most frequent cause of spinal cord dysfunction. There is little information on the exact pathophysiological mechanism responsible for the progressive loss of neural tissue in the spinal cord of such patients. In this study, we used the spinal hyperostotic mouse (twy/twy) as a suitable model of human spondylosis, and OPLL to investigate the cellular and molecular changes in the spinal cord. Mutant twy/twy mouse developed ossification of the ligamentum flavum at C2-C3 and exhibited progressive paralysis.

Size distribution curves of senile plaques in patients with Alzheimer’s disease: do plaques grow according to the log-normal model?

The size frequency distributions of diffuse, primitive and cored senile plaques (SP) were studied in single sections of the temporal lobe from 10 patients with Alzheimer’s disease (AD). The size distribution curves were unimodal and positively skewed. The size distribution curve of the diffuse plaques was shifted towards larger plaques while those of the neuritic and cored plaques were shifted towards smaller plaques. The neuritic/diffuse plaque ratio was maximal in the 11 – 30 micron size class and the cored/ diffuse plaque ratio in the 21 – 30 micron size class. The size distribution curves of the three types of plaque deviated significantly from a log-normal distribution. Distributions expressed on a logarithmic scale were ‘leptokurtic’, i.e. with excess of observations near the mean. These results suggest that SP in AD grow to within a more restricted size range than predicted from a log-normal model. In addition, there appear to be differences in the patterns of growth of diffuse, primitive and cored plaques. If neuritic and cored plaques develop from earlier diffuse plaques, then smaller diffuse plaques are more likely to be converted to mature plaques.

A comparison of the growth curves of the foliose lichen Parmelia conspersa determined by a cross-sectional study and by direct measurement

Changes in the radial growth rate (RGR mm/yr) through life were studied in thalli of the foliose lichen Parmelia conspersa by two methods: (1) a cross-sectional study (Study A) in which the RGR was measured in 60 thalli from 0.2 to 13 cm in diameter, and (2) by radial growth measurements over 4.5 years of fragments, consisting of a single major lobe, which were removed from large thalli and glued to pieces of slate (Study B). Both studies suggested there was a phase of increasing RGR in small thalli followed by a more constant phase, the latter beginning at approximately a thallus radius of 6-8 mm. However, in Study B significantly increased RGR was observed during the second 6-month growth period. This phase of growth was more likely to be due to an increase in lobe width than to an effect of climate. In addition, a lobe in a large thallus with both adjacent lobes removed significantly increased in width over 1 year compared with control lobes. These results suggest that (1) mean lobe width in a thallus may be determined by the intensity of marginal competition between adjacent lobes, and (2) changes in lobe width during the life of a lichen thallus may be a factor determining the establishment of the linear phase of growth in foliose lichens. © 1992.

Neural population coding is optimized by discrete tuning curves

The sigmoidal tuning curve that maximizes the mutual information for a Poisson neuron, or population of Poisson neurons, is obtained. The optimal tuning curve is found to have a discrete structure that results in a quantization of the input signal. The number of quantization levels undergoes a hierarchy of phase transitions as the length of the coding window is varied. We postulate, using the mammalian auditory system as an example, that the presence of a subpopulation structure within a neural population is consistent with an optimal neural code.

The retrograde delivery of adenovirus vector carrying the gene for brain-derived neurotrophic factor protects neurons and oligodendrocytes from apoptosis in the chronically compressed spinal cord of twy/twy mice

STUDY DESIGN: The twy/twy mouse undergoes spontaneous chronic mechanical compression of the spinal cord; this in vivo model system was used to examine the effects of retrograde adenovirus (adenoviral vector [AdV])-mediated brain-derived neurotrophic factor (BDNF) gene delivery to spinal neural cells. OBJECTIVE: To investigate the targeting and potential neuroprotective effect of retrograde AdV-mediated BDNF gene transfection in the chronically compressed spinal cord in terms of prevention of apoptosis of neurons and oligodendrocytes. SUMMARY OF BACKGROUND DATA: Several studies have investigated the neuroprotective effects of neurotrophins, including BDNF, in spinal cord injury. However, no report has described the effects of retrograde neurotrophic factor gene delivery in compressed spinal cords, including gene targeting and the potential to prevent neural cell apoptosis. METHODS: AdV-BDNF or AdV-LacZ (as a control gene) was injected into the bilateral sternomastoid muscles of 18-week old twy/twy mice for retrograde gene delivery via the spinal accessory motor neurons. Heterozygous Institute of Cancer Research mice (+/twy), which do not undergo spontaneous spinal compression, were used as a control for the effects of such compression on gene delivery. The localization and cell specificity of ß-galactosidase expression (produced by LacZ gene transfection) and BDNF expression in the spinal cord were examined by coimmunofluorescence staining for neural cell markers (NeuN, neurons; reactive immunology protein, oligodendrocytes; glial fibrillary acidic protein, astrocytes; OX-42, microglia) 4 weeks after gene injection. The possible neuroprotection afforded by retrograde AdV-BDNF gene delivery versus AdV-LacZ-transfected control mice was assessed by scoring the prevalence of apoptotic cells (terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling-positive cells) and immunoreactivity to active caspases -3, -8, and -9, p75, neurofilament 200 kD (NF), and for the oligodendroglial progenitor marker, NG2. RESULTS.: Four weeks after injection, the retrograde delivery of the LacZ marker gene was identified in cervical spinal neurons and some glial cells, including oligodendrocytes in the white matter of the spinal cord, in both the twy/twy mouse and the heterozygous Institute of Cancer Research mouse (+/twy). In the compressed spinal cord of twy/twy mouse, AdV-BDNF gene transfection resulted in a significant decrease in the number of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling-positive cells present in the spinal cord and a downregulation in the caspase apoptotic pathway compared with AdV-LacZ (control) gene transfection. There was a marked and significant increase in the areas of the spinal cord of AdV-BDNF-injected mice that were NF- and NG2-immunopositive compared with AdV-LacZ-injected mice, indicating the increased presence of neurons and oligodendrocytes in response to BDNF transfection. CONCLUSION: Our results demonstrate that targeted retrograde BDNF gene delivery suppresses apoptosis in neurons and oligodendrocytes in the chronically compressed spinal cord of twy/twy mouse. Further work is required to establish whether this method of gene delivery may provide neuroprotective effects in other situations of compressive spinal cord injury.

Blockade of interleukin 6 signaling improves the survival rate of transplanted bone marrow stromal cells and increases locomotor function in mice with spinal cord injury

Bone marrow stromal cells (BMSCs) have the potential to improve functional recovery in patients with spinal cord injury (SCI); however, they are limited by low survival rates after transplantation in the injured tissue. Our objective was to clarify the effects of a temporal blockade of interleukin 6 (IL-6)/IL-6 receptor (IL-6R) engagement using an anti-mouse IL-6R monoclonal antibody (MR16-1) on the survival rate of BMSCs after their transplantation in a mouse model of contusion SCI. MR16-1 cotreatment improved the survival rate of transplanted BMSCs, allowing some BMSCs to differentiate into neurons and astrocytes, and improved locomotor function recovery compared with BMSC transplantation or MR16-1 treatment alone. The death of transplanted BMSCs could be mainly related to apoptosis rather than necrosis. Transplantation of BMSC with cotreatment of MR16-1 was associated with a decrease of some proinflammatory cytokines, an increase of neurotrophic factors, decreased apoptosis rates of transplanted BMSCs, and enhanced expression of survival factors Akt and extracellular signal-regulated protein kinases 1/2. We conclude that MR16-1 treatment combined with BMSC transplants helped rescue neuronal cells and axons after contusion SCI better than BMSCs alone by modulating the inflammatory/immune responses and decreasing apoptosis. © 2013 by the American Association of Neuropathologists, Inc.

The prevalence and phenotype of activated microglia/macrophages within the spinal cord of the hyperostotic mouse (twy/twy) changes in response to chronic progressive spinalcord compression:implications for human cervical compressive myelopathy

Background:Cervical compressive myelopathy, e.g. due to spondylosis or ossification of the posterior longitudinal ligament is a common cause of spinal cord dysfunction. Although human pathological studies have reported neuronal loss and demyelination in the chronically compressed spinal cord, little is known about the mechanisms involved. In particular, the neuroinflammatory processes that are thought to underlie the condition are poorly understood. The present study assessed the localized prevalence of activated M1 and M2 microglia/macrophages in twy/twy mice that develop spontaneous cervical spinal cord compression, as a model of human disease.Methods:Inflammatory cells and cytokines were assessed in compressed lesions of the spinal cords in 12-, 18- and 24-weeks old twy/twy mice by immunohistochemical, immunoblot and flow cytometric analysis. Computed tomography and standard histology confirmed a progressive spinal cord compression through the spontaneously development of an impinging calcified mass.Results:The prevalence of CD11b-positive cells, in the compressed spinal cord increased over time with a concurrent decrease in neurons. The CD11b-positive cell population was initially formed of arginase-1- and CD206-positive M2 microglia/macrophages, which later shifted towards iNOS- and CD16/32-positive M1 microglia/macrophages. There was a transient increase in levels of T helper 2 (Th2) cytokines at 18 weeks, whereas levels of Th1 cytokines as well as brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and macrophage antigen (Mac) -2 progressively increased.Conclusions:Spinal cord compression was associated with a temporal M2 microglia/macrophage response, which may act as a possible repair or neuroprotective mechanism. However, the persistence of the neural insult also associated with persistent expression of Th1 cytokines and increased prevalence of activated M1 microglia/macrophages, which may lead to neuronal loss and demyelination despite the presence of neurotrophic factors. This understanding of the aetiopathology of chronic spinal cord compression is of importance in the development of new treatment targets in human disease. © 2013 Hirai et al.

Is randomisation necessary for measuring defocus curves in pre-presbyopes?

Purpose: Defocus curves are used to evaluate the subjective range of clear vision of presbyopic corrections such as in eyes implanted with accommodating intraocular lenses (IOLs). This study determines whether letter sequences and/or lens presentation order ought to be randomised when measuring defocus curves. Methods: Defocus curves (range +2.00DS to -2.00DS) were measured on 18 pre-presbyopic subjects (mean age 24.1 ± 4.2 years) for six combinations of sequential or randomised positive or negative lens progression and non-randomised or randomised letter sequences. The letters were presented on a computerised logMAR chart at 6 m. Results: Overall there was a statistically significant difference between the six combinations (ANOVA, p < 0.05) attributable to the combination of non-randomised letters with non-randomised lens progression from negative to positive defocus (p < 0.01). There was no statistically significant difference in defocus curve measurements if both letters and lens order were randomised compared to if only one of these variables was randomised (p > 0.05). Non-randomised letters, with a sequential lens progression from negative to positive, was significantly different to all other combinations when compared individually (Student's T-test, p < 0.003 on all comparisons), and was confirmed as the sole source of the overall significant difference. There was no statistically significant difference if both lens presentation order and letter sequences were randomised compared to if only one or the other of these variables was randomised. Conclusion: Non-randomised letters and non-randomised lens progression on their own did not affect the subjective amplitude of accommodation as measured by defocus curves, although their combination should be avoided. © 2007 British Contact Lens Association.

Approximation of Experimental Data by Bezier Curves

Very often the experimental data are the realization of the process, fully determined by some unknown function, being distorted by hindrances. Treatment and experimental data analysis are substantially facilitated, if these data to represent as analytical expression. The experimental data processing algorithm and the example of using this algorithm for spectrographic analysis of oncologic preparations of blood is represented in this article.

Spinal motor neurite outgrowth over glial scar inhibitors is enhanced by coculture with bone marrow stromal cells

Background context Transplantation of bone marrow cells into spinal cord lesions promotes functional recovery in animal models, and recent clinical trials suggest possible recovery also in humans. The mechanisms responsible for these improvements are still unclear. Purpose To characterize spinal cord motor neurite interactions with human bone marrow stromal cells (MSCs) in an in vitro model of spinal cord injury (SCI). Study design/setting Previously, we have reported that human MSCs promote the growth of extending sensory neurites from dorsal root ganglia (DRG), in the presence of some of the molecules present in the glial scar, which are attributed with inhibiting axonal regeneration after SCI. We have adapted and optimized this system replacing the DRG with a spinal cord culture to produce a central nervous system (CNS) model, which is more relevant to the SCI situation. Methods We have developed and characterized a novel spinal cord culture system. Human MSCs were cocultured with spinal motor neurites in substrate choice assays containing glial scar-associated inhibitors of nerve growth. In separate experiments, MSC-conditioned media were analyzed and added to spinal motor neurites in substrate choice assays. Results As has been reported previously with DRG, substrate-bound neurocan and Nogo-A repelled spinal neuronal adhesion and neurite outgrowth, but these inhibitory effects were abrogated in MSC/spinal cord cocultures. However, unlike DRG, spinal neuronal bodies and neurites showed no inhibition to substrates of myelin-associated glycoprotein. In addition, the MSC secretome contained numerous neurotrophic factors that stimulated spinal neurite outgrowth, but these were not sufficient stimuli to promote spinal neurite extension over inhibitory concentrations of neurocan or Nogo-A. Conclusions These findings provide novel insight into how MSC transplantation may promote regeneration and functional recovery in animal models of SCI and in the clinic, especially in the chronic situation in which glial scars (and associated neural inhibitors) are well established. In addition, we have confirmed that this CNS model predominantly comprises motor neurons via immunocytochemical characterization. We hope that this model may be used in future research to test various other potential interventions for spinal injury or disease states. © 2014 Elsevier Inc. All rights reserved.

On the Automorphism Groups of some AG-Codes Based on Ca;b Curves

*Partially supported by NATO.

On The Brill-noether Theory of Spanned Vector Bundles on Smooth Curves

Here we study the integers (d, g, r) such that on a smooth projective curve of genus g there exists a rank r stable vector bundle with degree d and spanned by its global sections.