Benefits of low-frequency attenuation of baha® in single-sided sensorineural deafness

To investigate the effect of low-frequency attenuation of Bone-Anchored Hearing Aids (Bahas) in users with single-sided sensorineural deafness (SSD). The underlying notion is that low-frequency sounds up to approximately 1500 Hz reach the contralateral ear without significant attenuation and that Bahas tend to show more distortion at lower frequencies. Furthermore, to transmit low frequencies, higher moving masses are needed when compared with high frequencies.

Vaccination-induced functional competence of circulating human tumor-specific CD8 T-cells

T-cells specific for foreign (e.g., viral) antigens can give rise to strong protective immune responses, whereas self/tumor antigen-specific T-cells are thought to be less powerful. However, synthetic T-cell vaccines composed of Melan-A/MART-1 peptide, CpG and IFA can induce high frequencies of tumor-specific CD8 T-cells in PBMC of melanoma patients. Here we analyzed the functionality of these T-cells directly ex vivo, by multiparameter flow cytometry. The production of multiple cytokines (IFNγ, TNFα, IL-2) and upregulation of LAMP-1 (CD107a) by tumor (Melan-A/MART-1) specific T-cells was comparable to virus (EBV-BMLF1) specific CD8 T-cells. Furthermore, phosphorylation of STAT1, STAT5 and ERK1/2, and expression of CD3 zeta chain were similar in tumor- and virus-specific T-cells, demonstrating functional signaling pathways. Interestingly, high frequencies of functionally competent T-cells were induced irrespective of patient's age or gender. Finally, CD8 T-cell function correlated with disease-free survival. However, this result is preliminary since the study was a Phase I clinical trial. We conclude that human tumor-specific CD8 T-cells can reach functional competence in vivo, encouraging further development and Phase III trials assessing the clinical efficacy of robust vaccination strategies.

Detection of prion protein gene polymorphisms in Baltic breeds of sheep

A total of 167 sheep belonging to the Estonian whiteheaded mutton, Estonian blackheaded mutton, Lithuanian coarsewool native, Lithuanian blackface and Latvian darkheaded mutton breeds, and a population of sheep kept isolated on the Estonian island of Ruhnu, were sequence-analysed for polymorphisms in the prion protein (PrP) gene, to determine their genotype and the allele frequencies of polymorphisms in PrP known to confer resistance to scrapie. A 939 base pair fragment of exon 3 from the PrP gene was amplified by pcr and analysed by direct sequencing. For animals showing polymorphism at two nucleotide positions, both haplotypes of these double-heterozygous genotypes were further verified by pcr cloning and sequence analysis. Known polymorphisms were observed at codons 136, 154 and 171, and six different haplotypes (arr, ahq, arh, ahr, arq and vrq) were determined. On the basis of these polymorphisms, the six populations of sheep possessed the resistant arr haplotype at different frequencies. The high-risk arq haplotype occurred in high frequencies in all six populations, but vrq, the haplotype carrying the highest risk, occurred at low frequencies and in only three of the populations.

Influence of transrectal and transabdominal ultrasound examination on salivary cortisol, heart rate, and heart rate variability in mares

Pregnancy diagnostics in equine reproduction are routinely performed using transrectal ultrasonography, although it is also possible to visualize the fetus by transabdominal ultrasound examinations from the 90th day of gestation onward. We hypothesized that ultrasound examinations may stress the mare and that the gestational stage status and lactation may influence the mare's stress reaction. To investigate the stress reaction, 25 thoroughbred mares of different age, pregnancy and lactational status underwent a transrectal examination. In pregnant mares, an additional transabdominal examination was performed. Salivary cortisol concentration, mean heart rate, and heart rate variability of mares were assessed to evaluate the reactions of hypothalamic–pituitary–adrenal (HPA) axis and of the autonomic nervous system. Significant differences were observed between lactating and nonlactating mares; with a lower responsiveness to stress in lactating mares. The transrectal ultrasound examination in nonlactating mares induced a significant increase in salivary cortisol (P < 0.05), and in the heart rate variability parameter, ratio of low to high frequencies (P < 0.05). This reflects an activation of the HPA axis and a shift to more sympathetic dominance. In contrast, a transabdominally performed pregnancy check did not induce an activation of the HPA axis over basal level but increased the mean heart rate and low to high frequency ratio. The results of this study indicate that checks of advanced pregnancies can be easily performed by transabdominal ultrasonography. With regard to animal welfare, this technique should be preferred during midgestation in nonlactating mares.

Long-lasting reactivity and high frequency of drug-specific T cells after severe systemic drug hypersensitivity reactions

BACKGROUND: Drug-reactive T cells are involved in most drug-induced hypersensitivity reactions. The frequency of such cells in peripheral blood of patients with drug allergy after remission is unclear. OBJECTIVE: We determined the frequency of drug-reactive T cells in the peripheral blood of patients 4 months to 12 years after severe delayed-type drug hypersensitivity reactions, and whether the frequency of these cell differs from the frequency of tetanus toxoid-reactive T cells. METHODS: We analyzed 5 patients with delayed-type drug hypersensitivity reactions, applying 2 methods: quantification of cytokine-secreting T cells by enzyme-linked immunospot (ELISpot), and fluorescent dye 5,6-carboxylfluorescein diacetate succinimidyl ester (CFSE) intensity distribution analysis of drug-reactive T cells. RESULTS: Frequencies found were between 0.02% and 0.4% of CD4(+) T cells reacting to the respective drugs measured by CFSE analysis, and between 0.01% and 0.08% of T cells as determined by ELISpot. Reactivity was seen neither to drugs to which the patients were not sensitized nor in healthy individuals after stimulation with any of the drugs used. CONCLUSION: About 1:250 to 1:10,000 of T cells of patients with drug allergy are reactive to the relevant drugs. This frequency of drug-reactive T cells is higher than the frequency of T cells able to recognize recall antigens like tetanus toxoid in the same subjects. A substantial frequency could be observed as long as 12 years later in 1 patient even after strict drug avoidance. Patients with severe delayed drug hypersensitivity reactions are therefore potentially prone to react again to the incriminated drug even years after strict drug avoidance.

Volume dependence of high-frequency respiratory mechanics in healthy adults

Respiratory system input impedance (Zrs) at low to medium frequencies below 100 Hz, and study of its volume dependence, have been used extensively to quantify airway and tissue mechanics. Zrs at high oscillation frequencies including the first antiresonant frequency (far,1) may contain important information about airway mechanics. Changes in high-frequency Zrs with lung volume have not been studied. The volume-dependent behavior of high-frequency Zrs, specifically far,1 and respiratory system resistance at first antiresonance (Rrs(far,1)), was characterized in 16 healthy adults. Zrs was measured with a forced oscillation signal (5-302.5 Hz) through a wavetube setup. To track Zrs, subjects performed slow deep inspiratory and expiratory maneuvers over 30-s measurements, during which average impedance was calculated over 0.4-s intervals, with successive overlapping estimates every 0.156 s. Flow was measured using a pneumotachometer and integrated to obtain volume. Transpulmonary pressure dependence (Ptp) of Zrs was separately determined in five subjects. Both far,1 and Rrs(far,1) decreased with increasing lung volume and Ptp, consistent with an increase in airway caliber and decreased airway wall compliance as volume increased. These characterizations provide insight into airway mechanics, and are furthermore a necessary first step toward determining whether volume dependence of the first antiresonance is altered in disease.

Negative impact of the noseclip on high-frequency respiratory impedance measurements

The noseclip is conventionally used in lung function testing to prevent leakage via the nasal compartments. However, some subjects exhibit a velum-opening reflex which may affect results. We performed forced oscillation measurements at frequencies (8-256 Hz) that include the first antiresonance, comparing the noseclip with a cotton wool nose plug to eliminate upper airway contribution. Three sets of measurements were made in 18 adults: with and without noseclip, and with cotton wool. Velum opening during noseclip measurements was monitored using a nasal pressure transducer. A significantly greater proportion of subjects produced a characteristic distortion to the first antiresonance with the noseclip than with either no noseclip or with cotton wool. Distortion of the spectrum coincided with the transmission of oscillations into the nasal cavity. Thus, the noseclip cannot be used in high-frequency forced oscillation measurements because of the velum reflex. The cotton wool plug offers a simple alternative. This effect has unknown impact in other lung function tests.

Pregnancy induces numerical and functional changes of CD4+CD25 high regulatory T cells in patients with rheumatoid arthritis

OBJECTIVE: In a prospective study we investigated whether numerical and functional changes of CD4+CD25(high) regulatory T cells (Treg) were associated with changes of disease activity observed during pregnancy and post partum in patients with rheumatoid arthritis (RA). METHODS: The frequency of CD4+CD25(high) T cells was determined by flow cytometry in 12 patients with RA and 14 healthy women during and after pregnancy. Fluorescence-activated cell sorting (FACS) was used to sort CD4+CD25(high) T cells and CD4+CD25- T cells were stimulated with anti-CD3 and anti-CD28 monoclonal antibodies alone or in co-culture to investigate proliferation and cytokine secretion. RESULTS: Frequencies of CD4+CD25(high) Treg were significantly higher in the third trimester compared to 8 weeks post partum in patients and controls. Numbers of CD4+CD25(high) Treg inversely correlated with disease activity in the third trimester and post partum. In co-culture experiments significantly higher amounts of IL10 and lowered levels of tumour necrosis factor (TNF)alpha and interferon (IFN)gamma were found in supernatants of the third trimester compared to postpartum samples. These findings were independent from health or disease in pregnancy, however postpartum TNFalpha and IFN gamma levels were higher in patients with disease flares. CONCLUSION: The amelioration of disease activity in the third trimester corresponded to the increased number of Treg that induced a pronounced anti-inflammatory cytokine milieu. The pregnancy related quantitative and qualitative changes of Treg suggest a beneficial effect of Treg on disease activity.

Can quantitative EEG measures predict clinical outcome in subjects at Clinical High Risk for psychosis? A prospective multicenter study

BACKGROUND Prediction studies in subjects at Clinical High Risk (CHR) for psychosis are hampered by a high proportion of uncertain outcomes. We therefore investigated whether quantitative EEG (QEEG) parameters can contribute to an improved identification of CHR subjects with a later conversion to psychosis. METHODS This investigation was a project within the European Prediction of Psychosis Study (EPOS), a prospective multicenter, naturalistic field study with an 18-month follow-up period. QEEG spectral power and alpha peak frequencies (APF) were determined in 113 CHR subjects. The primary outcome measure was conversion to psychosis. RESULTS Cox regression yielded a model including frontal theta (HR=1.82; [95% CI 1.00-3.32]) and delta (HR=2.60; [95% CI 1.30-5.20]) power, and occipital-parietal APF (HR=.52; [95% CI .35-.80]) as predictors of conversion to psychosis. The resulting equation enabled the development of a prognostic index with three risk classes (hazard rate 0.057 to 0.81). CONCLUSIONS Power in theta and delta ranges and APF contribute to the short-term prediction of psychosis and enable a further stratification of risk in CHR samples. Combined with (other) clinical ratings, EEG parameters may therefore be a useful tool for individualized risk estimation and, consequently, targeted prevention.

Radiometric Method for Emissivity Retrieval in High Reflective Materials

High reflective materials in the microwave region play a very important role in the realization of antenna reflectors for a broad range of applications, including radiometry. These reflectors have a characteristic emissivity which needs to be characterized accurately in order to perform a correct radiometric calibration of the instrument. Such a characterization can be performed by using open resonators, waveguide cavities or by radiometric measurements. The latter consists of comparative radiometric observations of absorbers, reference mirrors and the sample under test, or using the cold sky radiation as a direct reference source. While the first two mentioned techniques are suitable for the characterization of metal plates and mirrors, the latter has the advantages to be also applicable to soft materials. This paper describes how, through this radiometric techniques, it is possible to characterize the emissivity of the sample relative to a reference mirror and how to characterize the absolute emissivity of the latter by performing measurements at different incident angles. The results presented in this paper are based on our investigations on emissivity of a multilayer insulation material (MLI) for space mission, at the frequencies of 22 and 90 GHz.

High prevalence of hereditary thrombotic thrombocytopenic purpura in Central Norway: from clinical observation to evidence.

BACKGROUND Hereditary thrombotic thrombocytopenic purpura (TTP) caused by ADAMTS13 mutations is a rare, but serious condition. The prevalence is unknown, but seems to be high in Norway. OBJECTIVES To identify all patients with hereditary TTP in Central Norway and to investigate the prevalence of hereditary TTP and the population frequencies of two common ADAMTS13 mutations. Patients/Methods Patients were identified in a cross-sectional study within Central Norway Health Region by means of three different search strategies. Frequencies of ADAMTS13 mutations, c.4143_4144dupA and c.3178 C>T (p.R1060W) were investigated in a population-based cohort (500 alleles) and in healthy blood donors (2104 alleles) by taking advantage of the close neighbourhood of the ADAMTS13 and ABO blood group gene loci. The observed prevalence of hereditary TTP was compared to the rates of ADAMTS13 mutation carriers in different geographical regions. RESULTS We identified 11 families with hereditary TTP in Central Norway during the 10-year study period. The prevalence of hereditary TTP in Central Norway was 16.7 x 10(-6) . The most prevalent mutation was c.4143_4144dupA, accounting for two thirds of disease causing alleles among patients and having an allelic frequency of 0.33% in the Central, 0.10% in the Western, and 0.04% in the Southeastern Norwegian population. The allelic frequency of c.3178 C>T (p.R1060W) in the population was even higher (0.3-1%), but this mutation was infrequent among patients, with no homozygous cases. CONCLUSIONS We found a high prevalence of hereditary TTP in Central Norway and an apparently different penetrance of ADAMTS13 mutations. This article is protected by copyright. All rights reserved.

Preparatory studies for a high-precision Penning-trap measurement of the 163Ho electron capture Q-value

The ECHo Collaboration (Electron Capture 163Ho aims to investigate the calorimetric spectrum following the electron capture decay of 163Ho to determine the mass of the electron neutrino. The size of the neutrino mass is reflected in the endpoint region of the spectrum, i.e., the last few eV below the transition energy. To check for systematic uncertainties, an independent determination of this transition energy, the Q-value, is mandatory. Using the TRIGA-TRAP setup, we demonstrate the feasibility of performing this measurement by Penning-trap mass spectrometry. With the currently available, purified 163Ho sample and an improved laser ablation mini-RFQ ion source, we were able to perform direct mass measurements of 163Ho and 163Dy with a sample size of less than 1017 atoms. The measurements were carried out by determining the ratio of the cyclotron frequencies of the two isotopes to those of carbon cluster ions using the time-of-flight ion cyclotron resonance method. The obtained mass excess values are ME(163Ho)= −66379.3(9) keV and ME(163Dy)= −66381.7(8) keV. In addition, the Q-value was measured for the first time by Penning-trap mass spectrometry to be Q = 2.5(7) keV.

Distinct roles of cortical and pallidal β and γ frequencies in hemiparkinsonian and dyskinetic rats.

Enhanced β band (βB) activity, which is suppressed by levodopa (LD) treatment, has been demonstrated within the basal ganglia (BG) of Parkinson's disease (PD) patients. However, some data suggest that Parkinsonian symptoms are not directly related to this brain frequency and therefore, its causative role remains questionable. A less explored phenomenon is the link between the γ band (γB) and PD phenomenology. Here, we monitored the development of the oscillatory activity during chronic LD depletion and LD treatment in Parkinsonian and levodopa-induced dyskinesia (LID) in rats. We found a significant and bilateral power increase in the high βB frequencies (20-30Hz) within the first 10days after 6-hydroxydopamine (6-OHDA) lesion, which was in accordance with a significant depletion of dopaminergic fibers in the striatum. We also observed a clear-cut γB increase during LD treatment. The development of LID was characterized by a slight increase in the cumulative power of βB accompanied by a large augmentation in the γB frequency (60-80Hz). This latter effect reached a plateau in the frontal cortex bilaterally and the left globus pallidus after the second week of LD treatment. Our data suggest that the βB parallels the emergence of Parkinsonian signs and can be taken as a predictive sign of DA depletion, matching TH-staining reduction. On the other hand, the γB is strictly correlated to the development of LID. LD treatment had an opposite effect on βB and γB, respectively.