Impact of air gap, range shifter, and delivery technique on skin dose in proton therapy.

OBJECTIVE: Side effects of radiation therapy may include skin damage. The surface dose is of great interest and contains the buildup effect. In particular, the proton therapy community requires further experimental data to quantify doses in the surface region. This specification includes the skin dose, which is defined according to ICRU Report No. 39 at 70 µm water equivalent depth. The aim of this study is to gather more knowledge of the skin dose by varying key parameters defined by the patient treatment plan. This consists of clinical aspects such as the influence of the air gap, the application of a range shifter (RS), or the proton delivery technique. MATERIAL/METHODS: Skin doses were determined with a PTW 23391 extrapolation chamber with three thin Kapton® entrance windows operated as a conventional ionization chamber. The impact on the skin dose for quasi-monoenergetic pencil beam scanning (PBS) proton beams was evaluated for clinical air gaps between 3.5 and 51.1 cm. The differences in skin dose were assessed by irradiating equivalent fields with an RS of 51 mm water equivalent thickness (RS51) and without. Furthermore, the delivery techniques PBS, uniform scanning (US), and double scattering (DS) were compared by defining a spread-out Bragg peak (SOBP). TOPAS (V.3.1.2) was used to model an IBA nozzle with PBS and to score dose to water at the surface of a water phantom. RESULTS: For the monoenergetic fields without the application of the RS the skin dose was constant down to an air gap of 6.2 cm. A lower air gap of 3.5 cm showed a variation in skin dose by up to 2.4% compared to the results obtained with larger air gaps. With the inserted RS51 an increase in the skin dose was found for air gaps smaller than 11.3 cm. Experimentally, a dose difference of 1.4% was recorded for an air gap of 6.2 cm by inserting an RS and none. With the Monte Carlo calculations the largest dose increase was observed at the air gap of 3.5 cm with 1.7% and 4.0% relative to the skin dose results without the RS and to the largest evaluated air gap of 51.1 cm, respectively. The SOBP comparison of the beam modalities at the measuring plane at the isocenter revealed higher skin doses without RS (including RS) by up to +1.9% (+1.5%) for DS and +1.3% (+1.1%) for US compared to PBS. For all three techniques an approx. 2% rise in skin dose was observed for the largest evaluated air gap of 37.7 cm to an air gap of 6.2 cm when using an RS51. CONCLUSION: The study investigated aspects of skin dose of a water equivalent phantom by varying key parameters of a proton treatment plan. Parameters like the RS, the air gap, and the delivery modality have an impact on the order of 4.0% for the skin dose at the depth of 70 µm. The increases in skin dose are the effects of the contribution of the increased electron fluence at small air gaps and the emitted hadronic particles produced by the RS.

Determination of surface dose in pencil beam scanning proton therapy.

PURPOSE/OBJECTIVE: Quantification of surface dose within the first few hundred water equivalent µm is challenging. Nevertheless, it is of large interest for the proton therapy community to study dose effects in the skin. The experimental determination is affected by the detector properties, such as the detector volume and material. The International Commission on Radiation Units and Measurements in its report 39 recommends assessing the skin dose at a depth of 0.07 mm. The aim of this study is the estimation of the absorbed dose at and around a depth of 70 µm. We used various dosimetric approaches in conjunction with proton pencil beam scanning delivery to determine the skin dose in a clinical setting. MATERIAL/METHODS: Five different detectors were tested for determining the surface dose in water: EBT3 and HD-V2 GAFCHROMIC™ radiochromic film, LiF:Mg,Ti thermoluminescent dosimeter, IBA PPC05 plane-parallel ionization chamber, and PTW 23391 extrapolation chamber. The irradiation setup consisted of quasi-monoenergetic scanned proton pencil beams with kinetic energies of 100, 150, and 226.7 MeV, respectively. Radiochromic films were placed within a vertical stack and in wedge geometry and were analyzed with FilmQA Pro™ adopting triple channel dosimetry. The extrapolation chamber PTW 23391, which served as a reference in the current work, was used in a conventional ionization chamber setup with a fixed electrode gap of 2 mm. Three Kapton® entrance windows with thicknesses of 25, 50, and 75 µm were employed. Thermoluminescent dosimeters were provided as powder and were pressed onto a sheet of aluminum. Furthermore, the Monte Carlo code TOol for PArticle Simulation (TOPAS) in version 3.1.p2 was used to model an IBA pencil beam scanning nozzle and score dose to water in a water phantom. RESULTS: The resulting depth dose curves were normalized to their 100% dose at the reference depth of 3 cm. We obtained the skin doses with the extrapolation chamber and with TOPAS. For the experimental approach this resulted in 79.7 ± 0.3%, 86.0 ± 0.6%, and 87.1 ± 0.1% for the proton energies 100, 150, and 226.7 MeV, respectively. The results for TOPAS were 80.1 ± 0.2% (100 MeV), 87.1 ± 0.5% (150 MeV), and 86.9 ± 0.4% (226.7 MeV), respectively. Based on the experimental results of the skin dose, we provided a clinically relevant surface extrapolation factor for the common measurement methods. This allows the result of the first measurement depth of a detector to be scaled to the dose at the skin depth. Most practical would be the use of the surface extrapolation factor for the PPC05 chamber, due to its direct reading, the wide availability in clinics and the low uncertainties. The calculated factors were 0.986 ± 0.004 for 100 MeV, 0.961 ± 0.008 for 150 MeV, and 0.963 ± 0.003 for 226.7 MeV. CONCLUSIONS: In this study, dissimilar experimental approaches were evaluated with respect to measurements at depths close to the surface. The experimental depth dose curves are in good agreement with the simulation with TOPAS Monte Carlo. To the author's knowledge this was the first experimental determination of the skin dose according to the International Commission on Radiation Units and Measurements 39 definition in proton pencil beam scanning.

Free-breathing quantification of regional ventilation derived by phase-resolved functional lung (PREFUL) MRI.

PURPOSE: To test the feasibility of regional fully quantitative ventilation measurement in free breathing derived by phase-resolved functional lung (PREFUL) MRI in the supine and prone positions. In addition, the influence of T2 * relaxation time on ventilation quantification is assessed. METHODS: Twelve healthy volunteers underwent functional MRI at 1.5 T using a 2D triple-echo spoiled gradient echo sequence allowing for quantitative measurement of T2 * relaxation time. Minute ventilation (ΔV) was quantified by conventional fractional ventilation (FV) and the newly introduced regional ventilation (VR), which corrects volume errors due to image registration. ΔVFV versus ΔVVR and ΔVVR versus ΔVVR with T2 * correction were compared using Bland-Altman plots and correlation analysis. The repeatability and physiological plausibility of all measurements were tested in the supine and prone positions. RESULTS: On global and regional scales a strong correlation was observed between ΔVFV versus ΔVVR and ΔVVR versus ΔVVRT2* (r > 0.93); however, regional Bland-Altman analysis showed systematic differences (p < 0.0001). Unlike ΔVVRT2* , ΔVVR and ΔVFV showed expected physiologic anterior-posterior gradients, which decreased in the supine but not in the prone position at second measurement during 3 min in the same position. For all quantification methods a moderate repeatability (coefficient of variation <20%) of ventilation was found. CONCLUSION: A fully quantified regional ventilation measurement using ΔVVR in free breathing is feasible and shows physiologically plausible results. In contrast to conventional ΔVFV, volume errors due to image registration are eliminated with the ΔVVR approach. However, correction for the T2 * effect remains challenging.

Characterization of the thrombin generation profile in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a multisystemic inflammatory autoimmune disorder. Thrombotic events occur at a higher incidence among SLE patients. The investigation of thrombin generation (TG) with calibrated automated thrombogram (CAT) test as a global hemostasis assay is applicable for the overall functional assessment of the hemostasis. The aim of this study was to characterize the hemostatic alterations observed in SLE by CAT assay. In this study, CAT parameters and basic coagulation parameters of SLE patients (n = 22) and healthy control subjects (n = 34) were compared. CAT area under the curve (i.e., endogenous thrombin potential) was lower than normal in SLE (807 vs. 1,159 nM*min, respectively), whereas other CAT parameters (peak, lag time, time to peak, and velocity index) and the basic coagulation tests were within the normal range. The presence of anti-phospholipid antibodies and the applied therapy was not associated with hemostasis parameters in SLE. We concluded that the reported high risk of thrombosis is not related to TG potential.

Comparison of two commercial kits and an in-house ELISA for the detection of equine rotavirus in foal feces.

Group A rotaviruses (RVA) are important infectious agents associated with diarrhea in the young of several animal species including foals. Currently, a variety of diagnosis methods are commercially available, like ELISA, latex agglutination and immunochromatographic assays. These commercial tests are mainly designed for the detection of human RVA; its applicability in veterinary diagnosis has been poorly studied. The aim of this study was to compare the sensitivity and specificity of two commercial diagnostic kits, Pathfinder™ Rotavirus and FASTest Rota® strip, with an in-house KERI ELISA, for the detection of equine RVA. A total of 172 stool samples from Thoroughbred foals with diarrhea were analyzed. The presence of equine RVA in samples in which only one of the three methods showed positive results was confirmed by RT-PCR. A sample was considered "true positive" when RVA was detected by at least two of the methods, and "true negative" when it tested negative by the three assays. Following these criteria, 50 samples were found positive and 122 were found negative, and were handled as reference population for the assay validation. Pathfinder™ Rotavirus assay showed 32% sensitivity and 97% specificity, FASTest Rota® strip, 92% sensitivity and 97% specificity, and KERI ELISA, 76% sensitivity and 93% specificity. Pathfinder™ Rotavirus showed 77%, FASTest Rota® strip 95%, and KERI ELISA 88% accuracy to correctly classify the samples as equine RVA positive or negative. Pathfinder failed specifically to detect equine RVA G3P12I6 genotype; such performance might be related to the specificity of the monoclonal antibody included in this kit. According to our results, differences among VP6 genotypes could influence the sensitivity to detect equine RVA in foal feces, and thus assay validation of diagnostic kits for each species is necessary. In conclusion, FASTest Rota® strip is more suitable than ELISA Pathfinder™ Rotavirus for the screening of rotavirus infection in foals. The KERI ELISA showed an acceptable performance, and could be considered a proper economic alternative for equine RVA diagnosis.

Frequency of primary cutaneous lymphoma variants in Austria: retrospective data from a dermatology referral centre between 2006 and 2013.

BACKGROUND: Primary cutaneous lymphomas (PCL) are a heterogenous group of rare lymphoid neoplasms with incomplete information on global and regional prevalence. The recently introduced lymphoma classifications define distinctive clinicopathological disease entities that should allow for more accurate epidemiological assessment. OBJECTIVE: The aim of this study was to evaluate the prevalence and clinical spectrum of PCL diagnosed and treated at the Department of Dermatology and Venereology in St. Pölten, Lower Austria, a dermatology referral centre providing secondary and tertiary care for a population of about 600 000. METHODS: In this retrospective study pathology reports, electronically archived between 2006 and 2013, were screened for the terms lymphoma, mycosis fungoides (MF) and lymphomatoid papulosis (LyP). Patients were diagnosed according to the current WHO-EORTC classification for cutaneous lymphomas and results were compared with data from European, US and Asian centres. RESULTS: Among 86 patients with PCL (age 58.3 ± 17.35 years, mean ± SD; women 38%, n = 33; men 62%, n = 53) 83% (n = 71) were classified as cutaneous T-cell lymphomas (CTCL) and 17% (n = 15) as cutaneous B-cell lymphomas (CBCL). Nine patients with CTCL showed associated haematological disorders and malignomas. Among 47 MF patients following variants were observed: pilotropic MF (n = 2), follicular mucinosis (n = 1), unilesional MF (n = 1), large-cell transformation (n = 3), erythrodermic MF (n = 1), poikilodermatous MF (n = 2) and posttransplant lymphoproliferative disorder (CD8(+) MF with gamma/delta phenotype after renal transplantation) (n = 1). One patient had MF concurrent with lymphomatoid papulosis. The group of CBCL comprised six cases (40%) of PCMZL and PCFCL each, 20% (n = 3) were classified as PCLBCL, LT. CONCLUSION: This study for the first time provides data on the distribution of PCL clinicopathologic variants and stages according to the latest classification and staging systems in an Austrian referral centre.

Elevated tibiofemoral articular contact stress predicts risk for bone marrow lesions and cartilage damage at 30 months.

OBJECTIVE: As cartilage loss and bone marrow lesions (BMLs) are associated with knee joint pain and structural worsening, this study assessed whether non-invasive estimates of articular contact stress may longitudinally predict risk for worsening of knee cartilage morphology and BMLs. DESIGN: This was a longitudinal cohort study of adults aged 50-79 years with risk factors for knee osteoarthritis. Baseline and follow-up measures included whole-organ magnetic resonance imaging score (WORMS) classification of knee cartilage morphology and BMLs. Tibiofemoral geometry was manually segmented on baseline magnetic resonance imaging (MRI), and three-dimensional (3D) tibiofemoral point clouds were registered into subject-specific loaded apposition using fixed-flexion knee radiographs. Discrete element analysis (DEA) was used to estimate mean and peak contact stresses for the medial and lateral compartments. The association of baseline contact stress with worsening cartilage and BMLs in the same subregion over 30 months was assessed using conditional logistic regression. RESULTS: Subjects (N = 38, 60.5% female) had a mean ± standard deviation (SD) age and body mass index (BMI) of 63.5 ± 8.4 years and 30.5 ± 3.7 kg/m2 respectively. Elevated mean articular contact stress at baseline was associated with worsening cartilage morphology and worsening BMLs by 30 months, with odds ratio (OR) [95% confidence interval (CI)] of 4.0 (2.5, 6.4) and 6.6 (2.7, 16.5) respectively. Peak contact stress also was significantly associated with worsening cartilage morphology and BMLs {1.9 (1.5, 2.3) and 2.3 (1.5, 3.6)}(all P < 0.0001). CONCLUSIONS: Detection of higher contact stress 30 months prior to structural worsening suggests an etiological role for mechanical loading. Estimation of articular contact stress with DEA is an efficient and accurate means of predicting subregion-specific knee joint worsening and may be useful in guiding prognosis and treatment.

Strong evidence for the influence of solar cycles on a Late Miocene lake system revealed by biotic and abiotic proxies.

The Late Miocene paleogeography of central Europe and its climatic history are well studied with a resolution of c. 106 years. Small-scale climatic variations are yet unresolved. Observing past climatic change of short periods, however, would encourage the understanding of the modern climatic system. Therefore, past climate archives require a resolution on a decadal to millennial scale. To detect such a short-term evolution, a continuous 6-m-core of the Paleo-Lake Pannon was analyzed in 1-cm-sample distance to provide information as precise and regular as possible. Measurements of the natural gamma radiation and magnetic susceptibility combined with the total abundance of ostracod shells were used as proxies to estimate millennial- to centennial scale environmental changes during the mid-Tortonian warm period. Patterns emerged, but no indisputable age model can be provided for the core, due to the lack of paleomagnetic reversals and the lack of minerals suitable for absolute dating. Therefore, herein we propose another method to determine a hypothetic time frame for these deposits. Based on statistical processes, including Lomb-Scargle and REDFIT periodograms along with Wavelet spectra, several distinct cyclicities could be detected. Calculations considering established off-shore sedimentation rates of the Tortonian Vienna Basin revealed patterns resembling Holocene solar-cycle-records well. The comparison of filtered data of Miocene and Holocene records displays highly similar patterns and comparable modulations. A best-fit adjustment of sedimentation rate results in signals which fit to the lower and upper Gleissberg cycle, the de Vries cycle, the unnamed 500-year- and 1000-year-cycles, as well as the Hallstatt cycle. Each of these cycles has a distinct and unique expression in the investigated environmental proxies, reflecting a complex forcing-system. Hence, a single-proxy-analysis, as often performed on Holocene records, should be considered cautiously as it might fail to capture the full range of solar cycles.

Stereology of the neocortex in Odontocetes: qualitative, quantitative, and functional implications.

We investigated the quantitative morphology of the neocortex (gray matter) in 2 toothed whale (odontocete) species (harbor porpoise, Phocoena phocoena; bottlenose dolphin, Tursiops truncatus) with stereological methods. The 4 primary projection areas (motor, somatosensory, auditory, and visual fields) are analyzed for their cell densities in layers III and V with standard design-based stereology methods. Along cortical areas M1, S1, A1, and V1 in Tursiops, neuron density is always higher in layer III than in layer V, whereas the data in Phocoena are variable. Moreover, neuron density in layer III is generally around 1.5 times higher in Tursiops than in Phocoena. Maximal density values are seen in layer III of A1 and V1 in Tursiops and the ratio of layer III/layer V density is maximal in A1 of this species. Thus, layer III could have a higher capacity in the bottlenose dolphin with regard to intrinsic connectivity. Extant knowledge on toothed whale neurobiology and behavior suggests that quantitative/stereological differences between the 2 odontocete species regarding the neuron density of standard cortical units may be correlated with specific adaptations to their respective habitats. In contrast to layers V and VI which mainly serve as an executive system, layer III could represent an intermediate level in sensory and premotor processing which works more tangentially in the cortices via horizontal connections with other cortical areas, respectively. The generally higher density of cortical layer III in Tursiops suggests a higher connectivity of this layer in view of the more agile and complicated behavior of these gregarious animals including versatile phonation by complex sound and ultrasound signals.

Combined antenna and localized plasmon resonance in Raman scattering from random arrays of silver-coated, vertically aligned multiwalled carbon nanotubes.

The electric field enhancement associated with detailed structure within novel optical antenna nanostructures is modeled using the surface integral equation technique in the context of surface-enhanced Raman scattering (SERS). The antennae comprise random arrays of vertically aligned, multiwalled carbon nanotubes dressed with highly granular Ag. Different types of "hot-spot" underpinning the SERS are identified, but contrasting characteristics are revealed. Those at the outer edges of the Ag grains are antenna driven with field enhancement amplified in antenna antinodes while intergrain hotspots are largely independent of antenna activity. Hot-spots between the tops of antennae leaning towards each other also appear to benefit from antenna amplification.

Infectious agents and B cell tolerance breakdown.

The role of infectious agents in autoimmune diseases genesis is still a matter of debate. Several observations have suggested that autoimmune diseases may be initiated or worsened by infections (review by Kivity et al., 2009). However, there is no clear understanding of the underlying mechanisms. In particular, autoantibody production during infections could be the result of the non specific activation of "natural" autoreactive B cells that produce only low-affinity antibodies (Lacroix-Desmazes et al., 1998). A relevant hypothesis making the link between infections and autoimmune diseases could be the progressive genesis of more affine autoreactive B cells that could be involved in different pathogenic conditions. The major purpose of our work is therefore to study the breakdown of B cell tolerance and the ability for autoreactive B cells,especially low reactive B cells, to engage in an affinity maturation process during infections.We have created a new autoreactive B cell model allowing a relevant study of affinity maturation process. In this intermediate affinity SWHEL X HEL2x autoreactive model, knock-in B cells (Taki etal., 1993) express a B cell receptor highly specific for Hen-Egg Lysozyme (HEL) that recognizes HEL2x mutated auto-antigen with intermediate affinity (Phan et al., 2003; SWHEL model).Phenotypic analysis revealed that these autoreactive B cells are in a state of partial tolerance compared to the high affinity model (Phan et al., 2003; SWHEL X ML5 model) characterized by a strong anergy of HEL positive B cells.Experimental infections were performed with Borrelia burgdorferi, a Gram-negative spirochete,leading to sustained lymph nodes polyclonal B cell activation and hypergammaglobulinemia (Soulas et al., 2005). In SWHEL X HEL2x infected mice, in the presence of their auto-antigen,intermediate affinity autoreactive B cells are able to proliferate, to be activated, to enter into lymph nodes germinal centers and to produce IgM and IgG autoantibodies, although in low amounts.Moreover, IgG auto-antibodies in infected mice appear somatically mutated in the auto-antigen recognizing area. These data are consistent with a partial tolerance breakdown and the next experimental step will consist in checking the long-term survival of such activated autoreactive B cells and the impact of the observed mutations

The central vestibular complex in dolphins and humans: functional implications of Deiters' nucleus.

Toothed whales (Odontocetes; e.g., dolphins) are well-known for efficient underwater locomotion and for their acrobatic capabilities. Nevertheless, in relation to other mammals including the human and with respect to body size, their vestibular apparatus is reduced, particularly the semicircular canals. Concomitantly, the vestibular nerve and most of the vestibular nuclei are thin and small, respectively, in comparison with those in terrestrial mammals. In contrast, the lateral (Deiters') vestibular nucleus is comparatively well developed in both coastal and pelagic dolphins. In the La Plata dolphin (Pontoporia blainvillei) and the Common dolphin (Delphinus delphis), all of the vestibular nuclei are present and their topographic relations are similar to those in humans. Quantitative analysis, however, revealed that in the dolphin most of the nuclei (superior, medial, descending nucleus) are minute both in absolute and relative terms. Here, the only exception is the lateral vestibular nucleus, which is of comparable size in humans and Pontoporia and decidedly more voluminous in Delphinus. While the small size of the majority of the dolphin's vestibular nuclei correlates well with miniaturization of the semicircular canals, the size of Deiters' nucleus seems to support its relative independence from the vestibular system and a close functional relationship with the cerebellum. In comparison with findings in humans and other terrestrial mammals, both of these aspects seem to be related to the physical conditions of aquatic life and locomotion in three dimensions.

Biophysical parameters modification could overcome essential hearing gaps.

A majority of hearing defects are due to malfunction of the outer hair cells (OHCs), those cells within the mammalian hearing sensor (the cochlea) that provide an active amplification of the incoming signal. Malformation of the hearing sensor, ototoxic drugs, acoustical trauma, infections, or the effect of aging affect often a whole frequency interval, which leads to a substantial loss of speech intelligibility. Using an energy-based biophysical model of the passive cochlea, we obtain an explicit description of the dependence of the tonotopic map on the biophysical parameters of the cochlea. Our findings indicate the possibility that by suitable local modifications of the biophysical parameters by microsurgery, even very salient gaps of the tonotopic map could be bridged.

A generalization of the van-der-Pol oscillator underlies active signal amplification in Drosophila hearing.

The antennal hearing organs of the fruit fly Drosophila melanogaster boost their sensitivity by an active mechanical process that, analogous to the cochlear amplifier of vertebrates, resides in the motility of mechanosensory cells. This process nonlinearly improves the sensitivity of hearing and occasionally gives rise to self-sustained oscillations in the absence of sound. Time series analysis of self-sustained oscillations now unveils that the underlying dynamical system is well described by a generalization of the van-der-Pol oscillator. From the dynamic equations, the underlying amplification dynamics can explicitly be derived. According to the model, oscillations emerge from a combination of negative damping, which reflects active amplification, and a nonlinear restoring force that dictates the amplitude of the oscillations. Hence, active amplification in fly hearing seems to rely on the negative damping mechanism initially proposed for the cochlear amplifier of vertebrates.

[Second reading of breast imaging at the hospital department of radiology: reasonable or waste of money?]. / Mammadiagnostische Zweitbefundung in der Radiologischen Klinik: sinnvoller Mehraufwand oder Ressourcenverschwendung?

PURPOSE: To assess the effect of a second diagnostic reading of breast imaging at a university department of radiology. MATERIAL AND METHODS: The diagnostic reports of first readers from different private radiology practices and the reports of second readers from the university department of radiology were compared with the histological results (n = 214) and outcome of follow-ups for 4 years (n = 74) in 236 patients (mean age 55 years). BI-RADS categories were used for this purpose. The initial examinations had been performed because of symptoms (n = 117), early detection outside an organized screening program (n = 102), evaluations following breast cancer therapy (n = 13) and unknown primary tumors (n = 4). In addition, the number of complementary examinations and the influence of a second reading on patient management were evaluated. RESULTS: A total of 140 lesions were malignant and 148 were benign. Of the 288 lesions, 49 % were classified identically in the second reading; 36 % (79/217) of the lesions initially classified as BI-RADS 4 and 5 were downgraded to benign; and 41 % (29/71) of the lesions classified as BI-RADS 1 to 3 were upgraded as suspected of being malignant. The kappa value between the first and second readers was 0.34 with respect to each BI-RADS category separately and 0.18 with respect to categories 1 to 3 (benign) versus 4 and 5 (malignant). A second reading increased the sensitivity from 81 % (114/140) to 96 % (135/140) and the specificity from 30 % (45/148) to 78 % (116/148). Second readers detected 23 additional malignant lesions, changed two lesions correctly classified as malignant to benign categories and caused 6 additional false-positive findings. In all, 38 surgical biopsies could be prevented, one biopsy was erroneously delayed and three unnecessary excisional biopsies were initiated. In the study group, 49 MRI examinations revealed 5 additional malignant lesions and positively influenced surgical planning in 28 patients. In addition to these MRI examinations, 221 patients were examined using ultrasonography, 62 patients using complementary mammography, and 7 using galactography. CONCLUSION: The benefit of a second reading outweighs the expenditure.

Fast spike pattern detection using the correlation integral.

Conventional approaches to detect patterns in neuronal firing are template based. As the pattern length increases, the number of trial patterns to be tested leads to strongly divergent computational costs. To remedy this problem, we propose a different statistical approach, based on the correlation integral. Applications of our method to model and neuronal data demonstrate its reliability, even in the presence of noise. Additionally, our investigation provides interesting insights into the nature of correlation-integral anomalies.

Limit cycles, noise, and chaos in hearing.

Based on insight obtained from a newly developed cochlea model, we argue that noise-driven limit cycles are the basic ingredient in the mammalian cochlea hearing process. For insect audition, we provide evidence in favor of the persistence of this principle. We emphasize the role of bifurcations for the emergence of broad-range sound perception, both in the frequency and amplitude domain, and indicate that this crucially depends on the correct coupling between limit cycles. We review the limit-cycle coupling universality, and outline how it can be used to encode information. Cortical noise is the microscopic basis for this encoding, whereas chaos emerges as the macroscopic expression of computation being done in the network. Large neuron firing variability is one possible consequence of the proposed mechanism that may apply to both vertebrate and insect hearing.

Essential auditory contrast-sharpening is preneuronal.

Contrast-sharpening is a fundamental feature of mammalian sensory perception. Whereas visual contrast-sharpening has been fully understood in terms of the retinal neuronal wiring [DeVries, S. H. & Baylor, D. A. (1993) Cell 72, Suppl., 139-149], a corresponding explanation of auditory contrast-sharpening is still lacking. Here, we show that the essentials of auditory contrast-sharpening can be explained by using cochlear biophysics. This finding indicates that the phenomenon is basically of preneuronal origin.

Two-tone suppression and combination tone generation as computations performed by the Hopf cochlea.

Recent evidence suggests that the compressive nonlinearity responsible for the extreme dynamic range of the mammalian cochlea is implemented in the form of Hopf amplifiers. Whereas Helmholtz's original concept of the cochlea was that of a frequency analyzer, Hopf amplifiers can be stimulated not only by one, but also by neighboring frequencies. To reduce the resulting computational overhead, the mammalian cochlea is aided by two-tone suppression. We show that the laws governing two-tone suppression and the generation of combination tones naturally emerge from the Hopf-cochlea concept. Thus the Hopf concept of the cochlea reproduces not only local properties like the correct frequency response, but additionally accounts for more complex hearing phenomena that may be related to auditory signal computation.