Perception of aperiodicity in pathological voice

Although jitter, shimmer, and noise acoustically characterize all voice signals, their perceptual importance in naturally produced pathological voices has not been established psychoacoustically. To determine the role of these attributes in the perception of vocal quality, listeners were asked to adjust levels of jitter, shimmer, and the noise-to-signal ratio in a speech synthesizer, so that synthetic voices matched naturally produced tokens. Results showed that, although listeners agreed well in their judgments of the noise-to-signal ratio, they did not agree with one another in their chosen settings for jitter and shimmer. Noise-dependent differences in listeners' ability to detect changes in amounts of jitter and shimmer implicate both listener insensitivity and inability to isolate jitter and shimmer as separate dimensions in the overall pattern of aperiodicity in a voice as causes of this poor agreement. These results suggest that jitter and shimmer are not useful as independent indices of perceived vocal quality, apart from their acoustic contributions to the overall pattern of spectrally shaped noise in a voice. (c) 2005 Acoustical Society of America

Genes Involved in Systemic and Arterial Bed Dependent Atherosclerosis - Tampere Vascular Study

BACKGROUND: Atherosclerosis is a complex disease with hundreds of genes influencing its progression. In addition, the phenotype of the disease varies significantly depending on the arterial bed. METHODOLOGY/PRINCIPAL FINDINGS: We characterized the genes generally involved in human advanced atherosclerotic (AHA type V-VI) plaques in carotid and femoral arteries as well as aortas from 24 subjects of Tampere Vascular study and compared the results to non-atherosclerotic internal thoracic arteries (n=6) using genome-wide expression array and QRT-PCR. In addition we determined genes that were typical for each arterial plaque studied. To gain a comprehensive insight into the pathologic processes in the plaques we also analyzed pathways and gene sets dysregulated in this disease using gene set enrichment analysis (GSEA). According to the selection criteria used (>3.0 fold change and p-value <0.05), 235 genes were up-regulated and 68 genes down-regulated in the carotid plaques, 242 genes up-regulated and 116 down-regulated in the femoral plaques and 256 genes up-regulated and 49 genes down-regulated in the aortic plaques. Nine genes were found to be specifically induced predominantly in aortic plaques, e.g., lactoferrin, and three genes in femoral plaques, e.g., chondroadherin, whereas no gene was found to be specific for carotid plaques. In pathway analysis, a total of 28 pathways or gene sets were found to be significantly dysregulated in atherosclerotic plaques (false discovery rate [FDR] <0.25). CONCLUSIONS: This study describes comprehensively the gene expression changes that generally prevail in human atherosclerotic plaques. In addition, site specific genes induced only in femoral or aortic plaques were found, reflecting that atherosclerotic process has unique features in different vascular beds

Analysis of the properties of HAp coatings produced by RF magnetron sputtering

Hydroxyapatyt (HAp) jest fosforanem wapnia stosowanym jako biomateriał, który wspomaga odbudowę tkanki kostnej. Jednakże ze względu na jego niskie właściwości mechaniczne, a także anizotropię właściwości fizykochemicznych częściej stosowany jest w postaci powłok na implantach medycznych. Szereg technologii syntezy pozwala na wytwarzanie powłok fosforanów wapnia o szerokim wachlarzu składów stechiometrycznych oraz innych właściwości. Cechą wspólną powłok HAp wytwarzanych na podłożach metalicznych jest ich słaba adhezja spowodowana różnymi wartościami współczynników rozszerzalności cieplnej. Proponowaną w niniejszej pracy metodą poprawy adhezji powłok HAp do różnych podłoży stosowanych w medycynie jest zastosowanie międzywarstwy węglowej. Dzięki wysokiemu powinowactwu chemicznemu wapnia do fosforu możliwe jest uzyskanie lepszej adhezji warstwy HAp do podłoża, a przez to zapewnienie jej lepszych właściwości użytkowych. Warstwy hydroksyapatytowe otrzymano metodą rozpylania magnetronowego katody, wykonanej z proszku HAp, przy różnych parametrach prądowonapięciowych. W efekcie końcowym uzyskano warstwy kompozytowe C/HAp charakteryzujące się poprawioną adhezją i zróżnicowanymi właściwościami fizykochemicznymi. Strukturę i morfologię otrzymanych warstw badano przy wykorzystaniu SEM. Właściwości mechaniczne analizowano za pomocą metody nanoindentacji, grubość otrzymanych warstw mierzono za pomocą profilometru stykowego, natomiast swobodną energię powierzchniową metodą Owensa-Wendta przy wykorzystaniu analizy kąta zwilżania warstw. W wyniku przeprowadzonych badań opracowano typoszereg parametrów syntezy warstw HAp na podłożach metalicznych, modyfikowanych warstwą węglową, o poprawionych właściwościach użytkowych, adekwatnych dla konkretnej aplikacji.Hydroxyapatite (HAp) is a calcium phosphate used as a biomaterial, that supports the reconstruction of bone tissue. However, due to an anisotropy of its physicochemical properties and its low mechanical properties is often used in the form of thin coatings on medical implants. A number of synthesis technologies allows the production of calcium phosphate coatings characterized by a wide range of stoichiometric compositions and other properties. A common feature of HAp coatings produced on metal substrates is their poor adhesion caused by different coefficients of thermal expansion. Proposed in this paper method to improve adhesion of hydroxyapatite coatings to various substrates used in medicine is the application of carbon interlayer. High chemical affinity of calcium to carbon makes it possible to obtain a better adhesion of HAp layer to the substrate, and thus to ensure its better performance. Hydroxyapatite layers were manufactured by RF magnetron sputtering of cathode, which was made of pressed and sintered HAp powder, using different synthesis parameters. The final result are obtained C/HAp composite layers characterized by improved adhesion and variety of physicochemical properties. The structure and morphology of obtained layers were studied using SEM. The mechanical properties were analyzed using a nanoindentation method. Thickness of deposited layers was measured on the profilometer, whereas free surface energy (SEM) was investigated by Owens-Wendt method based on the measurement of layers contact angle. Following this study a range of synthesis parameters of HAp layers on substrates modified using carbon interlayer was worked out. Conducted investigation made it possible to obtain hydroxyapatite layers with improved performance characteristics that are adequate for the particular application

Optical coherence tomography angiography features in patients with idiopathic full-thickness macular hole, before and after surgical treatment

Tomasz Wilczyński,1 Anna Heinke,1 Agata Niedzielska-Krycia,1 Daria Jorg,2 Katarzyna Michalska-Małecka1,3 1University Clinical Center, University Hospital Medical University of Silesia, Katowice, Poland; 2Department of Sexuology, Woman&rsquo;s Health Institute, School of Health Sciences in Katowice, Medical University of Silesia, Katowice, Poland; 3Department of Ophthalmology, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland Purpose: To present optical coherence tomography (OCT) angiography features in patients with idiopathic full-thickness macular hole before and after vitrectomy. Study design: Prospective case series study. Materials and methods: Patients presenting with an idiopathic full-thickness macular hole (IMH) who underwent posterior vitrectomy with internal limiting membrane peeling and gas tamponade were included in the study. En face OCT and OCT angiography (OCTA) was performed pre- and postoperatively using 3&times;3 mm scans (Optovue, XR Avanti). Foveal avascular zone (FAZ) area, macular hole size (MHS), central retinal thickness (CRT), macular parafoveal choriocapillary flow area (MCFA), and fovea vessel density (FVDS) were measured and assessed using OCTA. Best-corrected visual acuity (BCVA) was examined before and 3 months after surgery. Results: Twenty-eight eyes of 28 patients were included in the study. The mean age of patient group was 68.28 years. The hole was closed in all eyes after the initial surgery. OCTA showed enlargement of FAZ and increased CRT in foveal area. Mean preoperative FAZ area was 0.39&plusmn;0.07 mm2. En face images of the middle retina showed a range of preoperative cystic patterns surrounding the hole. BCVA was improved from 0.1&plusmn;0.11 preoperatively to 0.42&plusmn;0.17 postoperatively. Mean FAZ area was reduced to 0.24&plusmn;0.07 mm2 postoperatively with resolution of macular hole and adjacent cystic areas. Mean CRT was reduced from 396&plusmn;62.6 &micro;m preoperatively to 272&plusmn;30.7 &micro;m postoperatively. After vitrectomy, the parafoveal choriocapillary flow area and FVDS of IMH eyes increased compared with the preoperative measurements. Conclusion: Quantitative evaluation of vascular and morphological changes following IMH surgery using OCTA shows the potential for recovery due to vascular and neuronal plasticity. OCTA showing vascular changes and their quantitative characteristics might be a useful tool for the assessment of macular holes before and after surgical treatment. Keywords: angio-OCT, imaging, idiopathic full thickness macular hole, vitrectomy, foveal avascular zone, central retinal thickness, choriocapillary flow area, foveal vessel densit

Non-physiological overexpression of the low density lipoprotein receptor (LDLr) gene in the liver induces pathological intracellular lipid and cholesterol storage

Background. Gene therapy of familial hypercholesterolemia (FH) requires successful transfer and lifelong expression of a functional low density lipoprotein receptor (LDLr) gene in the liver. Most of the vector systems currently employed for gene therapy use promoter elements which do not modulate transgene expression in a physiological manner. Methods. To study the in vivo effects of constitutive LDLr gene expression in the absence of interfering immunological reactions we established a new mouse model which combines homozygous LDLr deficiency and severe combined immune deficiency (SCID). Results. Adenovirus-mediated transfer and expression of the LDLr gene under the control of a commonly used virus-derived promoter (minimal CMV promoter) leads to prolonged reduction of serum cholesterol levels in LDLr-deficient SCID mice. During the first 10 days after gene therapy serum cholesterol drops to about 10% of pretherapeutic values. Serum cholesterol persists on this level for 2 weeks and then slowly starts to rise again. Four months after vector application serum levels have reached about 40% of pretherapeutic values. However, as early as 5 days after gene transfer, the histological analysis of liver sections revealed the formation of crystalline lipid/cholesterol deposits in the cytosol of hepatocytes. During the following 8 weeks the amount of crystals increased in size and density. The intracellular storage of lipid and cholesterol reduced cell viability and induced an accelerated loss of therapeutic DNA from mice livers as was shown in a comparative expression study employing a transgene with a different metabolic function (human alpha 1-antitrypsin). Conclusions. The non-physiological constitutive overexpression of an LDL receptor gene induces an imbalance between the speed of LDL uptake and metabolism which leads to pathological accumulation of lipids and cholesterol in hepatocytes. To protect cells from negative effects of LDLr overexpression, future vector design should consider the use of physiologically controlled expression elements