Circulating microRNAs as prognostic therapy biomarkers in head and neck cancer patients.

BACKGROUND: The prediction of therapy response in head and neck squamous cell cancer (HNSCC) requires biomarkers, which are also a prerequisite for personalised therapy concepts. The current study aimed to identify therapy-responsive microRNAs (miRNAs) in the circulation that can serve as minimally invasive prognostic markers for HNSCC patients undergoing radiotherapy. METHODS: We screened plasma miRNAs in a discovery cohort of HNSCC patients before therapy and after treatment. We further compared the plasma miRNAs of the patients to age- and sex-matched healthy controls. All miRNAs identified as biomarker candidates were then confirmed in an independent validation cohort of HNSCC patients and tested for correlation with the clinical outcome. RESULTS: We identified a signature of eight plasma miRNAs that differentiated significantly (P=0.003) between HNSCC patients and healthy donors. MiR-186-5p demonstrated the highest sensitivity and specificity to classify HNSCC patients and healthy individuals. All therapy-responsive and patient-specific miRNAs in plasma were also detectable in tumour tissues derived from the same patients. High expression of miR-142-3p, miR-186-5p, miR-195-5p, miR-374b-5p and miR-574-3p in the plasma correlated with worse prognosis. CONCLUSIONS: Circulating miR-142-3p, miR-186-5p, miR-195-5p, miR-374b-5p and miR-574-3p represent the most promising markers for prognosis and therapy monitoring in the plasma of HNSCC patients. We found strong evidence that the circulating therapy-responsive miRNAs are tumour related and were able to validate them in an independent cohort of HNSCC patients.

First results on angular distributions of thermal dileptons in nuclear collisions.

The NA60 experiment at the CERN Super Proton Synchrotron has studied dimuon production in 158A GeV In-In collisions. The strong excess of pairs above the known sources found in the complete mass region 0.2

Photon-photon entanglement with a single trapped atom.

An experiment is performed where a single rubidium atom trapped within a high-finesse optical cavity emits two independently triggered entangled photons. The entanglement is mediated by the atom and is characterized both by a Bell inequality violation of S=2.5, as well as full quantum-state tomography, resulting in a fidelity exceeding F=90%. The combination of cavity-QED and trapped atom techniques makes our protocol inherently deterministic--an essential step for the generation of scalable entanglement between the nodes of a distributed quantum network.

Fast excitation and photon emission of a single-atom-cavity system.

We report on the fast excitation of a single atom coupled to an optical cavity using laser pulses that are much shorter than all other relevant processes. The cavity frequency constitutes a control parameter that allows the creation of single photons in a superposition of two tunable frequencies. Each photon emitted from the cavity thus exhibits a pronounced amplitude modulation determined by the oscillatory energy exchange between the atom and the cavity. Our technique constitutes a versatile tool for future quantum networking experiments.

Evidence for radial flow of thermal dileptons in high-energy nuclear collisions.

The NA60 experiment at the CERN SPS has studied low-mass dimuon production in 158A GeV In-In collisions. An excess of pairs above the known meson decays has been reported before. We now present precision results on the associated transverse momentum spectra. The slope parameter Teff extracted from the spectra rises with dimuon mass up to the rho, followed by a sudden decline above. While the initial rise is consistent with the expectations for radial flow of a hadronic decay source, the decline signals a transition to an emission source with much smaller flow. This may well represent the first direct evidence for thermal radiation of partonic origin in nuclear collisions.

J/psi production in Indium-Indium collisions at 158 GeV/nucleon.

The NA60 experiment studies muon pair production at the CERN Super Proton Synchrotron. In this Letter we report on a precision measurement of J/psi in In-In collisions. We have studied the J/psi centrality distribution, and we have compared it with the one expected if absorption in cold nuclear matter were the only active suppression mechanism. For collisions involving more than approximately 80 participant nucleons, we find that an extra suppression is present. This result is in qualitative agreement with previous Pb-Pb measurements by the NA50 experiment, but no theoretical explanation is presently able to coherently describe both results.

Electrically evoked auditory brainstem response in cochlear implant users.

The waveforms and parameters of electrically evoked auditory brainstem responses, eeABRs, registered in cochlear implant users, were compared with those of acoustically evoked auditory brainstem responses, aeABRs, recorded in normally hearing subjects. The eeABRs, in contrast to the aeABRs, contained dubious Wave IV, while missed Waves VI and VII. The eeABRs possessed also shorter peak-latencies, shorter inter-peak intervals, and greater amplitudes. The revealed differences have been explained by the lack of cochlear mechanisms in cochlear implant recipients. On the other hand, eeABRs and aeABRs exhibited similar stimulus intensity dependence. Both had also lower thresholds, shorter peak-latencies, and greater amplitudes in females than in males.

Polarization-controlled single photons.

Vacuum-stimulated Raman transitions are driven between two magnetic substates of a 87Rb atom strongly coupled to an optical cavity. A magnetic field lifts the degeneracy of these states, and the atom is alternately exposed to laser pulses of two different frequencies. This produces a stream of single photons with alternating circular polarization in a predetermined spatiotemporal mode. MHz repetition rates are possible as no recycling of the atom between photon generations is required. Photon indistinguishability is tested by time-resolved two-photon interference.

[Discrimination of musical pitch with cochlear implants]. / Diskrimination musikalischer Tonhöhen bei Patienten mit Kochleaimplantat.

BACKGROUND: Numerous people with cochlear implants (CI) report difficulties in listening to music even though they understand speech quite well. One reason for this is a limited perception of pitch and timbre. In this study ability of adult CI subjects to discriminate musical pitch is investigated. PATIENTS AND METHODS: In two psychoacoustic experiments, each conducted in 10 adult CI subjects provided with MED-EL Combi 40+ cochlear implant devices and a control group of subjects with normal hearing, individual discrimination abilities for musical pitch perception were determined. To investigate the influence of the group of instruments on discrimination ability, stimuli representing four different groups of instruments were used: woodwind (clarinet), brass (trumpet), strings (violin) and keyboard instruments (piano). RESULTS: The discrimination thresholds determined varied between individual CI subjects, and on average they were significantly higher for the piano than for the other three instruments. CONCLUSIONS: The results show that in subjects with CI pitch perception differs from instrument to instrument and is in general worse than in persons with normal hearing.

First measurement of the rho spectral function in high-energy nuclear collisions.

We report on a precision measurement of low-mass muon pairs in 158 AGeV indium-indium collisions at the CERN SPS. A significant excess of pairs is observed above the yield expected from neutral meson decays. The unprecedented sample size of 360,000 dimuons and the good mass resolution of about 2% allow us to isolate the excess by subtraction of the decay sources. The shape of the resulting mass spectrum is consistent with a dominant contribution from pi+pi- -->rho -->mu+mu- annihilation. The associated space-time averaged spectral function shows a strong broadening, but essentially no shift in mass. This may rule out theoretical models linking hadron masses directly to the chiral condensate.

[Vestibular evoked muscle potentials dependency on neural origin and the location of an acoustic neuroma]. / Die vestibulär evozierten Muskelpotenziale in Abhängigkeit vom nervalen Ursprung und der Lage eines Akustikusneurinoms.

INTRODUCTION: Most acoustic neuromas (AN) originate from the inferior vestibular nerve (IVN). Vestibular evoked myogenic potentials (VEMP) are accepted as the only unilateral test for the function of the sacculus and the IVN. METHODS: The influence of the origin from the IVN and superior vestibular nerve (SVN), and the position of the AN in relation to the internal auditory canal on VEMPs was investigated. A total of 39 patients (aged: 30-67 years, mean: 53 years) were examined. The VEMPs were recorded on the activated sternocleidomastoid muscle and averaged over 200 stimuli. Tone bursts (95 dB nHL; 500 Hz; stimulation rate 5 Hz) were used to generate the VEMPs. RESULTS: The exact origin of the AN from the SVN or the IVN could be determined intraoperatively and correlated using VEMP in 28 patients. CONCLUSION: The origin of the AN has only a marginal influence on the results of VEMP measurements. The position of the AN in relation to the internal auditory canal seems to have more influence than the origin.

Semihard scattering unraveled from collective dynamics by two-pion azimuthal correlations in 158A GeV/c Pb+Au collisions.

Elliptic flow and two-particle azimuthal correlations of charged hadrons and high-p(T) pions (p(T)>1 GeV/c) have been measured close to midrapidity in 158A GeV/c Pb+Au collisions by the CERES experiment. Elliptic flow (v(2)) rises linearly with p(T) to a value of about 10% at 2 GeV/c. Beyond p(T) approximately 1.5 GeV/c, the slope decreases considerably, possibly indicating a saturation of v(2) at high p(T). Two-pion azimuthal anisotropies for p(T)>1.2 GeV/c exceed the elliptic flow values by about 60% in midcentral collisions. These nonflow contributions are attributed to nearside and back-to-back jetlike correlations, the latter exhibiting centrality dependent broadening.

Additional neuromagnetic source activity outside the auditory cortex in duration discrimination correlates with behavioural ability.

In magneto- and electroencephalographic experiments on an oddball paradigm we compared the components of the auditory evoked fields and potentials of "attend" with "nonattend" conditions in 17 subjects. The former consisted of the performance of a duration discrimination task, where we observed augmented activity for the auditory sustained response. A multiple source analysis showed this effect mainly stemming from a third source outside the auditory cortices. The dipole moment of this specific activation was increased by 150% under the attend condition. Having anatomical 3D MRI data sets of 12 subjects the likely location of the third source was shown to be within the area of the precuneus or the posterior cingulate gyrus, which, along with its waveform, suggests it to be a CNV equivalent. Further, the dipole moment is correlated significantly to the subjects' psychometrically derived discriminative abilities.

Enhanced production of low-mass electron-positron pairs in 40-AGeV Pb-Au collisions at the CERN SPS.

We report on first measurements of low-mass electron-positron pairs in Pb-Au collisions at the CERN SPS beam energy of 40 AGeV. The observed pair yield integrated over the range of invariant masses 0.2e(+)e(-) annihilation with a modified rho propagator. They may be linked to chiral symmetry restoration and support the notion that the in-medium modifications of the rho are more driven by baryon density than by temperature.

Intraocular microablation of choroidal tissue by a 308 nm AIDA excimer laser for RPE-transplantation in patients with age-related macular degeneration.

Age-related macular degeneration (AMD) is the leading cause of legal blindness in the western nations beyond 50 years of age. The most frequent cause for severe visual loss is the growth of neovascular membrances from the choroid into the subretinal space. This usually results in irreversible degeneration of the overlying retina. Surgical removal of the membrane is feasible, however, usually results in functional loss of apposing retinal photoreceptors since retinal pigment epithelial (RPE) cells are removed concurrently due to their tight adherence to the neovascular complex. Therefore, various attempts have been undertaken to fill the resulting RPE cell defect with either heterologous or autologous RPE cell transplants. So far cell survival, function and subsequent visual function has been disappointing. To minimize trauma and resulting dedifferentiation harvesting in the eye and transplantation in whole sheets and without temporary removal from the eyes would be desirable. This may be achieved by isolating grafts consisting of choroid, Bruch's membrance and RPE cells from the peripheral retina and transplantation of this graft under the neurosensory retina after removal of the choroidal neovascularization. However, the choroidal component of such a graft would be expected to interfere with diffusion of metabolites to and from the retina. Therefore, outcome would be expected to be better if the choroidal tissue would be removed before translocation. In preclinical experiments we used a 308 nm UV AIDA excimer laser to microablate choroidal tissue from such a graft in human donor eyes.

Universal pion freeze-out in heavy-ion collisions.

Based on an evaluation of data on pion interferometry and on particle yields at midrapidity, we propose a universal condition for thermal freeze-out of pions in heavy-ion collisions. We show that freeze-out occurs when the mean free path of pions lambda(f) reaches a value of about 1 fm, which is much smaller than the spatial extent of the system at freeze-out. This critical mean free path is independent of the centrality of the collision and beam energy from the Alternating Gradient Synchrotron to the Relativistic Heavy Ion Collider.

[Amplitude modulation following responses in audiological diagnostics]. / Amplitude Modulation Following Responses (AMFR) in der audiologischen Diagnostik.

The registration of brainstem potentials currently represents one of the most common methods in objective audiological diagnostics. However, regardless of their use, they are still known to possess important disadvantages, such as low specificity and validity in the lower frequency range due to broadband stimuli, or uncertainties due to the need for subjective evaluation. One potential solution to these problems could involve the registration of amplitude modulation following responses (AMFR). These potentials are being discussed much more regularly within the anglo-american literature due to their known frequency specificity within the high frequency range (resulting from a very narrow frequency band of stimulation), and also their ability to permit assessment of the hearing threshold at lower frequencies. Another additional advantage of AMFR results from the simple statistical verification of its presence.Extensive studies on the influence of both stimulating and recording parameters have also shown that the registration of AMFR could prove to be a very promising audiological tool, with past interest being focussed primarily on the optimal modulation frequency, the influence of vigilance of the generation of potentials, and the precise assessment of an objective threshold.

[Theoretical and physical aspects of excimer laser trabeculotomy (ELT) ab interno with the AIDA laser with a wave length of 308 mm]. / Theoretische und physikalische Aspekte der Excimer-Laser-Trabekulotomie (ELT) ab interno mit dem AIDA-Laser mit einer Wellenlänge von 308 nm.

Ablation of tissue structures containing and surrounded by water differs from tissue ablation at a surface, not only theoretically, but also in terms of outcome. In contrast to the situation often observed with surface ablation, it is shown that the trabecular meshwork in the anterior chamber of the eye can be ablated cleanly and accurately with the 308 nm Excimer laser without causing collateral thermal damage. The reason for this is that in the trabecular meshwork, the ratio of radiation-absorbing tissue to water--which absorbs very little energy--is very small. A marked cooling effect thus results, which permits the development of only a very small amount of collateral thermal damage at the boundaries of the ablation zone.

Linear versus non-linear recordings of transiently-evoked otoacoustic emissions--methodological considerations.

A non-linear technique is predominantly used for the recording of transiently-evoked otoacoustic emissions (TEOAEs). The aim of this study was to compare linear and non-linear TEOAE recordings. TEOAEs were recorded in 22 normal hearing subjects to clicks from 90 to 30 dB SPL in 10 dB steps with the ILO88 system using both linear and non-linear recording techniques. The non-linear recording technique reduces stimulus artifacts for early latencies, but total elimination could not be proved. Both artifact reduction and significant differences between the two kinds of TEOAE recordings were reduced for longer latencies and lower stimulus intensities. For longer latencies (>10 ms) there was no significant difference between "linear" and "non-linear" TEOAEs. A higher signal-to-noise ratio was found for "linear" TEOAEs, resulting in better identification and a higher test-retest correlation. The linear recording technique, which includes new methods of artifact cancellation in comparison to the mainly utilized non-linear recording technique, should be used especially in hearing screening.