The relationship between CA/C ratio and individual differences in dynamic accommodative responses while viewing stereoscopic images

The oculomotor synergy as expressed by the CA/C and AC/A ratios was investigated to examine its influence on our previous observation that whereas convergence responses to stereoscopic images are generally stable, some individuals exhibit significant accommodative overshoot. Using a modified video refraction unit while viewing a stereoscopic LCD, accommodative and convergence responses to balanced and unbalanced vergence and focal stimuli (BVFS and UBVFS) were measured. Accommodative overshoot of at least 0.3 D was found in 3 out of 8 subjects for UBVFS. The accommodative response differential (RD) was taken to be the difference between the initial response and the subsequent mean static steady-state response. Without overshoot, RD was quantified by finding the initial response component. A mean RD of 0.11 +/- 0.27 D was found for the 1.0 D step UBVFS condition. The mean RD for the BVFS was 0.00 +/- 0.17 D. There was a significant positive correlation between CA/C ratio and RD (r = +0.75, n = 8, p <0.05) for only UBVFS. We propose that inter-subject variation in RD is influenced by the CA/C ratio as follows: an initial convergence response, induced by disparity of the image, generates convergence-driven accommodation commensurate with the CA/C ratio; the associated transient defocus subsequently decays to a balanced position between defocus-induced and convergence-induced accommodations.

Fatigue crack propagation in nickel-base superalloys:effects of microstructure, load ratio, and temperature

The current state of knowledge and understanding of the long fatigue crack propagation behavior of nickel-base superalloys are reviewed, with particular emphasis on turbine disk materials. The data are presented in the form of crack growth rate versus stress intensity factor range curves, and the effects of such variables as microstructure, load ratio, and temperature in the near-threshold and Paris regimes of the curves, are discussed.

Detection of urinary bladder cancer cells using redox ratio and double excitation wavelengths autofluorescence

The optical redox ratio as a measure of cellular metabolism is determined by an altered ratio between endogenous fluorophores NADH and flavin adenine dinucleotide (FAD). Although reported for other cancer sites, differences in optical redox ratio between cancerous and normal urothelial cells have not previously been reported. Here, we report a method for the detection of cellular metabolic states using flow cytometry based on autofluorescence, and a statistically significant increase in the redox ratio of bladder cancer cells compared to healthy controls. Urinary bladder cancer and normal healthy urothelial cell lines were cultured and redox overview was assessed using flow cytometry. Further localisation of fluorescence in the same cells was carried out using confocal microscopy. Multiple experiments show correlation between cell type and redox ratio, clearly differentiating between healthy cells and cancer cells. Based on our preliminary results, therefore, we believe that this data contributes to current understanding of bladder tissue fluorescence and can inform the design of endoscopic probes. This approach also has significant potential as a diagnostic tool for discrimination of cancer cells among shed urothelial cells in voided urine, and could lay the groundwork for an automated system for population screening for bladder cancer.

Reductions of peak-to-average power ratio and optical beat interference in cost-effective OFDMA-PONs

The peak-to-average power ratio (PAPR) and optical beat interference (OBI) effects are examined thoroughly in orthogonal frequency-division multiplexing access (OFDMA)-passive optical networks (PONs) at a signal bit rate up to ∼ 20 Gb/s per channel using cost-effective intensity-modulation and direct-detection (IM/DD). Single-channel OOFDM and upstream multichannel OFDM-PONs are investigated for up to six users. A number of techniques for mitigating the PAPR and OBI effects are presented and evaluated including adaptive-loading algorithms such as bit/power-loading, clipping for PAPR reduction, and thermal detuning (TD) for the OBI suppression. It is shown that the bit-loading algorithm is a very efficient PAPR reduction technique by reducing it at about 1.2 dB over 100 Km of transmission. It is also revealed that the optimum method for suppressing the OBI is the TD + bit-loading. For a targeted BER of 1 × 10-3, the minimum allowed channel spacing is 11 GHz when employing six users. © 2013 Springer Science+Business Media New York.

Optical redox ratio and endogenous porphyrins in the detection of urinary bladder cancer:a patient biopsy analysis

Bladder cancer is among the most common cancers in the UK and conventional detection techniques suffer from low sensitivity, low specificity, or both. Recent attempts to address the disparity have led to progress in the field of autofluorescence as a means to diagnose the disease with high efficiency, however there is still a lot not known about autofluorescence profiles in the disease. The multi-functional diagnostic system "LAKK-M" was used to assess autofluorescence profiles of healthy and cancerous bladder tissue to identify novel biomarkers of the disease. Statistically significant differences were observed in the optical redox ratio (a measure of tissue metabolic activity), the amplitude of endogenous porphyrins and the NADH/porphyrin ratio between tissue types. These findings could advance understanding of bladder cancer and aid in the development of new techniques for detection and surveillance.

Diverse antiepileptic drugs increase the ratio of background synaptic inhibition to excitation and decrease neuronal excitability in neurones of the rat entorhinal cortex in vitro

Although most anti-epileptic drugs are considered to have a primary molecular target, it is clear that their actions are unlikely to be limited to effects on a single aspect of inhibitory synaptic transmission, excitatory transmission or voltage-gated ion channels. Systemically administered drugs can obviously simultaneously access all possible targets, so we have attempted to determine the overall effect of diverse agents on the balance between GABAergic inhibition, glutamatergic excitation and cellular excitability in neurones of the rat entorhinal cortex in vitro. We used an approach developed for estimating global background synaptic excitation and inhibition from fluctuations in membrane potential obtained by intracellular recordings. We have previously validated this approach in entorhinal cortical neurones [. Greenhill and Jones (2007a) Neuroscience 147:884-892]. Using this approach, we found that, despite their differing pharmacology, the drugs tested (phenytoin, lamotrigine, valproate, gabapentin, felbamate, tiagabine) were unified in their ability to increase the ratio of background GABAergic inhibition to glutamatergic excitation. This could occur as a result of decreased excitation concurrent with increased inhibition (phenytoin, lamotrigine, valproate), a decrease in excitation alone (gabapentin, felbamate), or even with a differential increase in both (tiagabine). Additionally, we found that the effects on global synaptic conductances agreed well with whole cell patch recordings of spontaneous glutamate and GABA release (our previous studies and further data presented here). The consistency with which the synaptic inhibition:excitation ratio was increased by the antiepileptic drugs tested was matched by an ability of all drugs to concurrently reduce intrinsic neuronal excitability. Thus, it seems possible that specific molecular targets among antiepileptic drugs are less important than the ability to increase the inhibition:excitation ratio and reduce overall neuronal and network excitability. © 2010 IBRO.

Biocomposites of non-crosslinked natural and synthetic polymers

Biocomposite films comprising a non-crosslinked, natural polymer (collagen) and a synthetic polymer, poly(var epsilon-caprolactone) (PCL), have been produced by impregnation of lyophilised collagen mats with a solution of PCL in dichloromethane followed by solvent evaporation. This approach avoids the toxicity problems associated with chemical crosslinking. Distinct changes in film morphology, from continuous surface coating to open porous format, were achieved by variation of processing parameters such as collagen:PCL ratio and the weight of the starting lyophilised collagen mat. Collagenase digestion indicated that the collagen content of 1:4 and 1:8 collagen:PCL biocomposites was almost totally accessible for enzymatic digestion indicating a high degree of collagen exposure for interaction with other ECM proteins or cells contacting the biomaterial surface. Much reduced collagen exposure (around 50%) was measured for the 1:20 collagen:PCL materials. These findings were consistent with the SEM examination of collagen:PCL biocomposites which revealed a highly porous morphology for the 1:4 and 1:8 blends but virtually complete coverage of the collagen component by PCL in the1:20 samples. Investigations of the attachment and spreading characteristics of human osteoblast (HOB) cells on PCL films and collagen:PCL materials respectively, indicated that HOB cells poorly recognised PCL but attachment and spreading were much improved on the biocomposites. The non-chemically crosslinked, collagen:PCL biocomposites described are expected to provide a useful addition to the range of biomaterials and matrix systems for tissue engineering.

Compatibilisation and stabilisation of immiscible polymer blends by reactive processing

The main objectives of this research were to develop optimised chemical compositions and reactive processing conditions for grafting a functional monomer maleic anhydride (MA) in polypropylene (PP), ethylene propylene diene monomer (EPDM) and mixtures of PP-EPDM, and to optimise synthetic routes for production of PP/EPDM copolymers for the purpose of compatibilisation of PP/EPDM blends. The MA-functionalisation was achieved using an internal mixer in the presence of low concentrations (less than 0.01 molar ratio) of a free radical initiator. Various methods were used to purify MA-functionalised PP and the grafting yield was determined using either FTIR or titrametry. The grafting yield of MA alone, which due to its low free-radical reactivity towards polymer macroradicals, was accompanied by severe degradation in the case of PP and crosslinking for EPDM. In the case of MA-functionalised PP/EPDM, both degradation and crosslinking occurred though not to a great extent. The use of tri-functional coagents e.g. trimethylopropane triacrylates (TRIS) with MA, led to high improvement of the grafting yield of MA on the polymers. This is almost certainly due to high free-radical activity of TRIS leading to copolymerisation of MA and TRIS which was followed by grafting of the copolymer onto the polymer backbone. In the case of PP, the use of coagent was also found to reduce the polymer degradation. PP/EPDM copolymers with optimum tensile properties were synthesised using a 'one-step' continues reactive processing procedure. This was achieved firstly by functionalisation of a mixture of PP (higher w/w ratio) and EPDM (low w/w ratio) with MA, in the presence of the coagent TRIS and a small concentration of a free radical initiator. This was then followed by an imidisation reaction with the interlinking agent hexamethylene diamine (HEMDA). Small amount of copolymers, up to 5 phr, which were interlinked with up to 15 phr of HEMDA, were sufficient to compatibilise PP/EPDM75/25 blends resulting in excellent tensile properties compared to binary PP/EPDM 75/25 blend. Improvement in blend's compatibility and phases-stabilisation (observed through tensile and SEM analysis) was shown in all cases with significant interphases adhesion improvement between PP and EPDM, and reduction in domain size across the fractured surface indicating efficient distribution of the compatibiliser.

Conformational analysis and dielectric relaxation of polycarbosilanes and related materials

The conformational characteristics of poly(dimethylsilmethylene), poly(dimethylsilethene), poly(dimethylsilethane) and a related material, poly(2,2,5,5-tetramethyl-1-oxa-2,5-disilapentane), have been investigated using the method of molecular mechanics. In this method, a quantitative analysis of the factors affecting the nature and magnitude of the bond rotation potentials governing their conformational behaviour has been undertaken. Along with their structural data, the results obtained were employed to calculate a variety of conformationally-dependent properties for these polymers, including the characteristic ratio, the dipole moment ratio and the mean-square radius of gyration. In addition, the dielectric relaxation behaviour of two samples of poly(2,2,5,5-tetramethyl-1-oxa-2,5-disilapentane) with molar masses Mw = 28000 and Mw = 46000 respectively, have been studied as a function of temperature (179K-205K) and frequency (100-105Hz). Activation energies for the α-relaxation process and Davidson-Cole empirical distribution factors have been calculated.

Quantitative assessment of the pharmacotherapy of biopolar disorder and schizophrenia

The work present in this thesis was aimed at assessing the efficacy of lithium in the acute treatment of mania and for the prophylaxis of bipolar disorder, and investigating the value of plasma haloperidol concentration for predicting response to treatment in schizophrenia. The pharmacogenetics of psychotropic drugs is critically appraised to provide insights into interindividual variability in response to pharmacotherapy, In clinical trials of acute mania, a number of measures have been used to assess the severity of illness and its response to treatment. Rating instruments need to be validated in order for a clinical study to provide reliable and meaningful estimates of treatment effects, Eight symptom-rating scales were identified and critically assessed, The Mania Rating Scale (MRS) was the most commonly used for assessing treatment response, The advantage of the MRS is that there is a relatively extensive database of studies based on it and this will no doubt ensure that it remains a gold standard for the foreseeable future. Other useful rating scales are available for measuring mania but further cross-validation and validation against clinically meaningful global changes are required. A total of 658 patients from 12 trials were included in an evaluation of the efficacy of lithium in the treatment of acute mania. Treatment periods ranged from 3 to 4 weeks. Efficacy was estimated using (i) the differences in the reduction in mania severity scores, and (ii) the ratio and difference in improvement response rates. The response rate ratio for lithium against placebo was 1.95 (95% CI 1.17 to 3.23). The mean number needed to treat was 5 (95% CI 3 to 20). Patients were twice as likely to obtain remission with lithium than with chlorpromazine (rate ratio = 1.96, 95% CI 1.02 to 3.77). The mean number needed to treat (NNT) was 4 (95% CI 3 to 9). Neither carbamazepine nor valproate was more effective than lithium. The response rate ratios were 1.01 (95% CI 0.54 to 1.88) for lithium compared to carbarnazepine and 1.22 (95% CI 0.91 to 1.64) for lithium against valproate. Haloperidol was no better than lithium on the basis of improvement based on assessment of global severity. The differences in effects between lithium and risperidone were -2.79 (95% CI -4.22 to -1.36) in favour of risperidone with respect to symptom severity improvement and -0.76 (95% CI -1.11 to -0,41) on the basis of reduction in global severity of disease. Symptom and global severity was at least as well controlIed with lithium as with verapamil. Lithium caused more side-effects than placebo and verapamil, but no more than carbamazepine or valproate. A total of 554 patients from 13 trials were included in the statistical analysis of lithium's efficacy in the prophylaxis of bipolar disorder. The mean follow-up period was 5-34 months. The relapse risk ratio for lithium versus placebo was 0.47 (95% CI 0.26 to 0.86) and the NNT was 3 (95% CI 2 to 7). The relapse risk ratio for lithium versus imipramine was 0.62 (95% CI 0.46 to 0.84) and the NNT was 4 (951% Cl 3 to 7), The combination of lithium and imipramine was no more effective than lithium alone. The risk of relapse was greater with lithium alone than with the lithium-divalproate combination. A risk difference of 0.60 (95% CI 0.21 to 0.99) and an NNT of 2 (95% CI 1 to 5) were obtained. Lithium was as effective as carbamazepine. Based on individual data concerning plasma haloperidol concentration and percent improvement in psychotic symptoms, our results suggest an acceptable concentration range of 11.20-30.30 ng/mL A minimum of 2 weeks should be allowed before evaluating therapeutic response. Monitoring of drug plasma levels seems not to be necessary unless behavioural toxicity or noncompliance is suspected. Pharmacokinetics and pharmacodynamics, which are mainly determined by genetic factors, contribute to interindividual and interethnic variations in clinical response to drugs. These variations are primarily due to differences in drug metabolism. Variability in pharmacokinetics of a number of drugs is associated with oxidation polymorphism. Debrisoquine/sparteine hydroxylase (CYP2D6) and the S-mephenytoin hydroxylase (CYP2C19) are polymorphic P450 enzymes with particular importance in psychopharmacotherapy. The enzymes are responsible for the metabolism of many commonly used antipsychotic and antidepressant drugs. The incidence of poor metabolisers of debrisoquine and S-mephenytoin varies widely among populations. Ethnic variations in polymorphic isoenzymes may, at least in part, explain ethnic differences in response to pharmacotherapy of antipsychotics and antidepressant drugs.

Microstructural analysis of surface and interface zones in concrete

Several of OPC paste and concrete specimens, with different mix proportions, were cast against CPF and impermeable formwork (IF) and the profiles of pore structure, microhardness and scratch hardness of the cover zone were established. The chloride ingress and the depth of carbonation of the surface zone of concrete cast against CPF and IF were investigated. The main mechanisms controlling the ECR processes and the factors affecting such treatment were critically reviewed. Subsequently, as a means of restoring passivation of steel embedded in carbonated concrete, such HCP specimens were subjected to ECR. The influence of ECR on the chemistry of the pore solution and the microstructure of the surface and the steel/cement past interface zones were also studied. The main findings of this investigation were as follows: (a) The thickness of the microstructure gradient of cover concrete is significantly decreased with increasing period of water curing but is relatively unaffected by curing temperature, w/e ratio and the use of cement replacement materials. (b) The scratch hardness technique was shown to be potentially useful for characterising the microstructure and microhardness gradients of the surface zone. (c) A relationship between the microstructure gradient and mass transport properties of the surface zone was established. (d) The use of CPF resulted in a significant reduction in porosity of both the cement paste matrix and the aggregate/cement paste transition zone, and a marked improvement in the resistance of the surface zone to carbonation and the ingress of chloride ions. (e) The ECR treatment resulted in a marked densification of the pore structure and in changes to the pore solution chemistry and the cement phases of near-surface and steel/cement paste transition zones. This effect was more pronounced with current density, period of treatment and particularly with the use of sodium phosphate as an electrolyte.

OCT retinal thickness ratios and frequency of follow-up in Wet AMD

Poster Introduction: In neovascular age-related macular degeneration (nAMD), optical coherence tomography (OCT) is an important tool to determine when intravitreal injections of ranibizumab should be administered. Current guidelines recommend that patients should be reviewed four weekly and OCT indications for further treatment include subretinal fluid and intraretinal fluid or cysts. Purpose: We have reviewed the OCT scans of subjects who have successfully responded to ranibizumab to look for factors that might predict which patients will not require injection and could have extended appointments. Method: This was a prospective study in which we observed for 6 consecutive months the OCT images of 28 subjects who had received intravitreal ranibizumab for nAMD and were judged to be clinically inactive at recruitment to the study. Ratios between full retinal thickness (FRT = neurosensory retina + outer reflective band) and outer reflective band (ORB) thickness at the fovea were calculated for each subject at the moment of entering the study and at each successive visit for 6 consecutive months. Results: Patients with lower FRT/ORB ratios were found to be less likely to require an additional injection of ranibizumab and no subject with a ratio of 1.75 or less needed further injections. Conclusion: This small pilot study suggests that on macular OCT, the FRT/ORB ratio, and in particular values of 1.75 or less, may prove to be a useful, practical tool when deciding the follow up period for subjects undergoing treatment with intravitreal ranibizumab for nAMD.

Preparation and characterisation of amino acids based trimethoprim salts

Trimethoprim (TMP) is a dihydrofolate reductase (DHFR) inhibitor which prevents the conversion of dihydrofolic acid into tetrahydrofolic acid, resulting in the depletion of the latter and leading to bacterial death. Oral bioavailability of TMP is hindered by both its low solubility and low permeability. This study aims to prepare novel salts of TMP using anionic amino acids; aspartic and glutamic acid as counter ions in order to improve solubility and dissolution. TMP salts were prepared by lyophilisation and characterized using FT-IR spectroscopy, proton nuclear magnetic resonance (1HNMR), Differential Scanning Calorimetry (DSC) and Thermogravimetric analysis (TGA). Both the amino acids formed salts with TMP in a 1:1 molar ratio and showed a 280 fold improvement in solubility. Investigation of the microbiological activity of the prepared salts against TMP sensitive Escherichia coli showed that the new salts not only retained antibacterial activity but also exhibited higher zone of inhibition which was attributed to improved physicochemical characters such as higher solubility and dissolution. The results are an important finding that could potentially impact on faster onset of antibacterial activity and reduced therapeutic dose when administered to patients. Studies are underway investigating the effect of ion-pairing TMP with amino acids on the permeability profile of the drug.

Sulforaphane restores cellular glutathione levels and reduces chronic periodontitis neutrophil hyperactivity in vitro

The production of high levels of reactive oxygen species by neutrophils is associated with the local and systemic destructive phenotype found in the chronic inflammatory disease periodontitis. In the present study, we investigated the ability of sulforaphane (SFN) to restore cellular glutathione levels and reduce the hyperactivity of circulating neutrophils associated with chronic periodontitis. Using differentiated HL60 cells as a neutrophil model, here we show that generation of extracellular O2 . - by the nicotinamide adenine dinucleotide (NADPH) oxidase complex is increased by intracellular glutathione depletion. This may be attributed to the upregulation of thiol regulated acid sphingomyelinase driven lipid raft formation. Intracellular glutathione was also lower in primary neutrophils from periodontitis patients and, consistent with our previous findings, patients neutrophils were hyper-reactive to stimuli. The activity of nuclear factor erythroid-2-related factor 2 (Nrf2), a master regulator of the antioxidant response, is impaired in circulating neutrophils from chronic periodontitis patients. Although patients' neutrophils exhibit a low reduced glutathione (GSH)/oxidised glutathione (GSSG) ratio and a higher total Nrf2 level, the DNA-binding activity of nuclear Nrf2 remained unchanged relative to healthy controls and had reduced expression of glutamate cysteine ligase catalytic (GCLC), and modifier (GCLM) subunit mRNAs, compared to periodontally healthy subjects neutrophils. Pre-treatment with SFN increased expression of GCLC and GCM, improved intracellular GSH/GSSG ratios and reduced agonist-activated extracellular O2 . - production in both dHL60 and primary neutrophils from patients with periodontitis and controls. These findings suggest that a deficiency in Nrf2-dependent pathways may underpin susceptibility to hyper-reactivity in circulating primary neutrophils during chronic periodontitis. © 2013 Dias et al.

Th1 immune responses can be modulated by varying dimethyldioctadecylammonium and distearoyl-sn-glycero-3-phosphocholine content in liposomal adjuvants

Objectives - Cationic liposomes of dimethyldioctadecylammonium bromide (DDA) combined with trehalose 6,6'-dibehenate (TDB) elicit strong cell-mediated and antibody immune responses; DDA facilitates antigen adsorption and presentation while TDB potentiates the immune response. To further investigate the role of DDA, DDA was replaced with the neutral lipid of distearoyl-sn-glycero-3-phosphocholine (DSPC) over a series of concentrations and these systems investigated as adjuvants for the delivery of Ag85B–ESAT-6-Rv2660c, a multistage tuberculosis vaccine. Methods - Liposomal were prepared at a 5?:?1 DDA–TDB weight ratio and DDA content incrementally replaced with DSPC. The physicochemical characteristics were assessed (vesicle size, zeta potential and antigen loading), and the ability of these systems to act as adjuvants was considered. Key findings - As DDA was replaced with DSPC within the liposomal formulation, the cationic nature of the vesicles decreases as does electrostatically binding of the anionic H56 antigen (Hybrid56; Ag85B-ESAT6-Rv2660c); however, only when DDA was completed replaced with DSPC did vesicle size increase significantly. T-helper 1 (Th1)-type cell-mediated immune responses reduced. This reduction in responses was attributed to the replacement of DDA with DSPC rather than the reduction in DDA dose concentration within the formulation. Conclusion - These results suggest Th1 responses can be controlled by tailoring the DDA/DSPC ratio within the liposomal adjuvant system.