An increase in the number of partially sighted people is one of the effects of population ageing. These people have great difficulties in gathering wayfinding information to move independently in an ...unfamiliar environment. Guide paths based on the luminance contrast between a strip and surrounding surfaces can be an effective device for mitigating these difficulties, but information provided by the scientific literature on guide paths cannot be usefully applied to the naturally coloured paving materials most commonly found in pedestrian urban spaces. This paper presents a simplified method for measuring the luminance contrast between a guide strip and its background using combinations of naturally coloured paving materials.
Pregabalin: a new anxiolytic Lauria-Horner, Bianca A; Pohl, Robert B
Expert opinion on investigational drugs,
04/2003, Letnik:
12, Številka:
4
Journal Article
Recenzirano
Pregabalin (S-+-3-isobutylgaba) was designed as a lipophilic GABA (γ-aminobutyric acid) analogue substituted at the 3′-position in order to facilitate diffusion across the blood-brain barrier. It was ...originally developed as an anticonvulsant agent, however it has been shown to be effective in the treatment of several disorders including hyperalgesia and behavioural disorders. Although its exact mode of action remains unclear, pregabalin interacts with the same binding site and has a similar pharmacological profile as its predecessor, gabapentin (1-aminomethyl cyclohexane acetic acid). Its main site of action appears to be on the α2δ subunit of voltage-dependent calcium channels, widely distributed throughout the peripheral and central nervous system. Pregabalin appears to produce an inhibitory modulation of neuronal excitability. In healthy volunteers, it is rapidly absorbed with peak blood concentrations within 1 h and it has a bioavailability of ∼ 90%. In preclinical trials of anticonvulsant activity, pregabalin is three to ten times more potent than gabapentin. It is well-tolerated and associated with dose-dependent adverse effects (ataxia, dizziness, headache and somnolence) that are mild-to-moderate and usually transient. There are no known pharmacokinetic drug-drug interactions reported to date. Preliminary animal and human studies showed beneficial effects in both ethological and conflict models of anxiety, as well as having some sleep-modulating properties. In Phase II and III trials, pregabalin shows promising anxiolytic action when compared to placebo in generalised anxiety disorder, social phobia and panic disorder.
Abstract Background and aims Obesity is often associated with an increased cardiovascular risk. The food industry and the associated research activities focus on formulating products that are a ...perfect mix between an adequate fat content and health. We evaluated whether a diet enriched with Bio-Oil Spread (SD), an olive oil-based innovative food, is cardioprotective in the presence of high-fat diet (HFD)-dependent obesity. Methods and Results Rats were fed for 16 weeks with normolipidic diet (ND; fat: 6.2%), HFD (fat: 42%), and ND enriched with SD (6.2% of fat + 35.8% of SD). Metabolic and anthropometric parameters were measured. Heart and liver structures were analyzed by histochemical examination. Ischemic susceptibility was evaluated on isolated and Langendorff-perfused cardiac preparations. Signaling was assessed by Western blotting. Compared to ND rats, HFD rats showed increased body weight and abdominal obesity, dyslipidemia, and impaired glucose tolerance. Morphological analyses showed that HFD is associated with heart and liver modifications (hypertrophy and steatosis, respectively), lesser evident in the SD group, together with metabolic and anthropometric alterations. In particular, IGF-1R immunodetection revealed a reduction of hypertrophy in SD heart sections. Notably, SD diet significantly reduced myocardial susceptibility against ischemia/reperfusion (I/R) with respect to HFD through the activation of survival signals (Akt, ERK1/2, and Bcl2). Systolic and diastolic performance was preserved in the SD group. Conclusions We suggest that SD may contribute to the prevention of metabolic disorders and cardiovascular alterations typical of severe obesity induced by an HFD, including the increased ischemic susceptibility of the myocardium. Our results pave the way to evaluate the introduction of SD in human alimentary guidelines as a strategy to reduce saturated fat intake.
The functional His452Tyr polymorphism in the 5HT2A receptor has been described to be associated with verbal memory in healthy adults, with worse episodic memory performances in Tyr452 (T) carriers. ...The aim of our study was to investigate a possible effect of this polymorphism on memory performances in Alzheimer disease (AD). We enrolled 169 patients affected by probable AD. 5HT2A genotype was determined as previously described. According to their genotype, patients were divided in T carriers ( n = 111) and non-carriers ( n = 69). We evaluated the possible effect of 5HT2A polymorphism on verbal memory tasks. A one-way MANOVA analysis did not show a positive interaction between the two groups ( p > 0.05) at the baseline and at the follow-up. Nevertheless, the analyses of the single-task effect showed lower performances for non-T carriers only in Rey's recognition task. Recent data reported poorer memory performances in healthy subjects carrying the T variant, in age-dependent manner (no differences between T vs. nT carriers were observed for age >50 years). In our AD sample, we did not find significant differences in verbal memory scores in T vs. nT carriers while a significant difference was found only in attentional task. At variance with that in healthy subjects, no correlation has been found between memory profiles of AD patients and His452Tyr polymorphism.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Silica thin films with embedded SnO2 nanoparticles have been grown on transparent substrates by the sol-gel method. Tin dioxide crystals with cassiterite structure are semiconductors with a wide band ...gap of ~3.6eV. Optical absorption spectroscopy in the near ultravioletavisible range has been exploited to probe nanostructuring features of such nanocrystals. The results show that the sintering conditions modify crystallite mean size and enable the occurrence of quantum confinement effects. The outcome is in accordance with transmission electron microscopy data conducted on analogous bulk samples.
Mass localization plays a crucial role in computer-aided detection (CAD) systems for the classification of suspicious regions in mammograms. In this article we present a completely automated ...classification system for the detection of masses in digitized mammographic images. The tool system we discuss consists in three processing levels: (a) Image segmentation for the localization of regions of interest (ROIs). This step relies on an iterative dynamical threshold algorithm able to select iso-intensity closed contours around gray level maxima of the mammogram. (b) ROI characterization by means of textural features computed from the gray tone spatial dependence matrix (GTSDM), containing second-order spatial statistics information on the pixel gray level intensity. As the images under study were recorded in different centers and with different machine settings, eight GTSDM features were selected so as to be invariant under monotonic transformation. In this way, the images do not need to be normalized, as the adopted features depend on the texture only, rather than on the gray tone levels, too. (c) ROI classification by means of a neural network, with supervision provided by the radiologist’s diagnosis. The CAD system was evaluated on a large database of 3369 mammographic images 2307 negative, 1062 pathological (or positive), containing at least one confirmed mass, as diagnosed by an expert radiologist. To assess the performance of the system, receiver operating characteristic (ROC) and free-response ROC analysis were employed. The area under the ROC curve was found to be
A
z
=
0.783
±
0.008
for the ROI-based classification. When evaluating the accuracy of the CAD against the radiologist-drawn boundaries, 4.23 false positives per image are found at 80% of mass sensitivity.
The mammography is the most effective procedure for an early diagnosis of the breast cancer. In this paper, an algorithm for detecting masses in mammographic images will be presented. The database ...consists of 3762 digital images acquired in several hospitals belonging to the MAGIC-5 collaboration (Medical Applications on a Grid Infrastructure Connection). A reduction of the whole image's area under investigation is achieved through a segmentation process, by means of a ROI Hunter algorithm, without loss of meaningful information. In the following classification step, feature extraction plays a fundamental role: some features give geometrical information, other ones provide shape parameters. Once the features are computed for each ROI, they are used as inputs to a supervised neural network with momentum. The output neuron provides the probability that the ROI is pathological or not. Results are provided in terms of ROC and FROC curves: the area under the ROC curve was found to be A Z =0.862plusmn0.007, and we get a 2.8 FP/Image at a sensitivity of 82%. This software is included in the CAD station actually working in the hospitals belonging to the MAGIC-5 Collaboration
Summary Score-driven models have recently been introduced as a general framework to specify time-varying parameters of conditional densities. The score enjoys stochastic properties that make these ...models easy to implement and convenient to apply in several contexts, ranging from biostatistics to finance. Score-driven parameter updates have been shown to be optimal in terms of locally reducing a local version of the Kullback–Leibler divergence between the true conditional density and the postulated density of the model. A key limitation of such an optimality property is that it holds only locally both in the parameter space and sample space, yielding to a definition of local Kullback–Leibler divergence that is in fact not a divergence measure. The current paper shows that score-driven updates satisfy stronger optimality properties that are based on a global definition of Kullback–Leibler divergence. In particular, it is shown that score-driven updates reduce the distance between the expected updated parameter and the pseudo-true parameter. Furthermore, depending on the conditional density and the scaling of the score, the optimality result can hold globally over the parameter space, which can be viewed as a generalization of the monotonicity property of the stochastic gradient descent scheme. Several examples illustrate how the results derived in the paper apply to specific models under different easy-to-check assumptions, and provide a formal method to select the link function and the scaling of the score.
We present the results of the analysis of the ultraviolet (UV) absorption edge of fluorine-modified sol-gel silica. UV transmission data, obtained by means of synchrotron radiation, have been ...analyzed in the spectral range 7.5–8.5
eV, with a spectral resolution of about 10
meV. Data on silica samples with different F content (from 0 to few 10
−
1
mol%) have been analyzed and compared with literature data on quartz and pure synthetic commercial silica. The analysis allows us to discriminate between the effects of the fluorine addition and those ascribable to structural peculiarities of the sol-gel networking. The estimated Urbach energy
E
U
(
T
=
0) ranges between 45 and 55
meV, higher that in crystalline quartz and lower than in commercial synthetic silica. The study of the temperature dependence of
E
U
(
T) shows that the fluorine modification of the silica network causes the lowering of the static disorder and the widening of the energy gap. However, there is also a relevant effect of the production process, since sol-gel silica samples show lower
E
U
values with respect to other types of silica, quite independently of the fluorine content. The analysis of the Raman spectra however shows that the starting amount of fluorine-modified molecular precursor influences the network condensation process, independently of the final fluorine content into the matrix.
Aim: Postprandial hyperglycaemia is a consequence of reduced first phase insulin response and is associated with increased cardiovascular risk and mortality. The aim of this proof-of-concept study ...was to investigate the safety and efficacy of treatment with buccal spray insulin (Oral-lyn™, Generex Biotechnology Corporation, Toronto, Ontario, Canada) on postprandial plasma glucose and insulin levels in subjects with impaired glucose tolerance (IGT). Methods: A total of 19 female and 12 male Caucasian subjects, 52.2 ± 13.5 (SD) years old, having a body mass index of 33.1 ± 6 (SD) kg/m² with confirmed IGT were included in the study. Subjects were randomized to take 4, 6 or 12 Oral-lyn puffs (1 puff = 1 s.c. rapid insulin UI) split into two equal doses each, one before and the second 30 min after a standard 75 g oral glucose tolerance test (OGTT). Glucose and insulin levels were measured at baseline and 30, 60, 90, 120 and 180 min afterwards. Results: Glucose fluctuations during OGTT were not modified by 4 or 6 Oral-lyn puffs. Treatment with 12 puffs was followed by 29.6% decrease in plasma glucose at 2 h and 26.8% decrease at 3 h, altogether p = 0.01. Considering all time points of the OGTT, there was a mean reduction of 15.8% in glucose levels. With 6 of the total 12 puffs used in group C there was a significant increase in the insulin levels during OGTT at 30 min (p < 0.04) but not at 2 or 3 h. No hypoglycaemic episodes were observed at any time points of the OGTT. Conclusions: This proof-of-concept study demonstrates that treatment with buccal spray insulin is a simple and valuable therapy for reducing postprandial hyperglycaemia in obese subjects with IGT. Importantly, this treatment is safe and none of the study subjects experienced hypoglycaemia.
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