Representation of echo roughness and its relationship to amplitude-modulation processing in the bat auditory midbrain

Bats use natural landmarks such as trees for orientation. Echoes reflected by a tree are stochastic and complex. The degree of irregular loudness fluctuations of perceived echoes, i.e. the echo roughness, may be used to classify natural objects reliably. Bats are able to discriminate and classify echoes of different roughness. A neural correlate of the psychophysical roughness sensitivity has been described in the auditory cortex of the bat Phyllostomus discolor . Here, the role of the inferior colliculus of P.    discolor is explored in the neural representation of echo roughness. Using extracellular recording techniques, responses were obtained to simulated stochastic echoes of different roughness. The representation of these irregular loudness fluctuations in echoes is compared to the representation of periodic loudness fluctuations elicited by sinusoidal amplitude modulation (SAM) and to the shape of the peri-stimulus time histogram in response to pure tones. About half the recorded units responded significantly differently to echoes with different roughness. Roughness sensitivity was related to the units' sensitivity to the depth of an SAM: units that responded best to strong SAMs also responded best to echoes of high roughness. In response to pure tones, these units were typically characterized as Onset units. In contrast to the auditory cortex experiments, the responses of many units in the inferior colliculus decreased with increasing echo roughness. These units typically preferred weak SAMs and showed a sustained response to pure tones. The data show that auditory midbrain sensitivity to SAM is an important prerequisite for the neural representation of echo roughness as an ecologically important echo-acoustic parameter.     

Computer-assisted colonoscopy (the NeoGuide Endoscopy System): results of the first human clinical trial ("PACE study")

OBJECTIVES: Unsedated colonoscopy is an uncomfortable procedure for most patients. Discomfort during colonoscopy is largely related to looping of the colonoscope, which displaces the colon from its native configuration and stretches attachments to the mesentery. A novel computer-assisted colonoscope utilizes a fully articulated, computer-controlled insertion tube. On manual insertion of the colonoscope, the position and angle of the scope's tip are encoded into a computer algorithm. As the colonoscope is advanced, the computer directs each successive segment to take the same shape that the tip had at a given insertion depth. The insertion tube thus changes its shape at different insertion depths in a "follow-the-leader" manner. METHODS: This initial clinical trial with this novel colonoscopy system was designed as a prospective, nonrandomized, unblinded, feasibility study. Three physicians of varying levels of experience participated in the study. RESULTS: Eleven consecutive patients (seven men, four women, age range 19-80) meeting inclusion criteria for screening or diagnostic colonoscopy were enrolled in the study. The cecum was reached in 10 consecutive patients (100%). Findings included diverticular disease in two cases and multiple colonic polyps in two cases. Postprocedure assessment at discharge, 48 h, and 30 days revealed no complications or adverse effects. Physician satisfaction and patient acceptance of this new technique were high. CONCLUSIONS: In this limited, first of its kind feasibility study, the computer-assisted colonoscope was shown to perform colonoscopy safely and effectively. The colonoscope's unique design limited loop formation during colonoscopy. Large-scale clinical trials are indicated.     

Cevimeline for the treatment of postirradiation xerostomia in patients with head and neck cancer

PURPOSE: To study the efficacy and safety of cevimeline in two double-blind trials (Studies 003 and 004) enrolling patients with head and neck cancer in whom xerostomia developed after radiotherapy. METHODS AND MATERIALS: Subjects were randomly assigned to receive cevimeline, 30 mg three times daily, or placebo for 12 weeks, with the possibility of dose escalation to 45 mg three times daily at 6 weeks. The primary efficacy endpoint was the patient's final global evaluation of oral dryness; change in unstimulated salivary flow was a secondary endpoint. RESULTS: Five hundred seventy subjects (284 in Study 003 and 286 in Study 004) were randomized. Significantly more cevimeline-treated subjects than placebo recipients (47.4% vs. 33.3%, p = 0.0162) in Study 003 reported improvement in dry mouth in the final global evaluation of oral dryness. No significant difference between groups in the final global evaluation was seen in Study 004, in which a high placebo response rate of 47.6% was observed. In both studies, cevimeline-treated subjects had significantly greater increases in the objective measure of unstimulated salivary flow than placebo recipients (p = 0.0093 [Study 003] and p = 0.0215 [Study 004]), whereas no significant differences in stimulated salivary flow were observed. The most frequent adverse event was increased sweating. CONCLUSION: Cevimeline was well tolerated by patients with xerostomia after radiotherapy for head and neck cancer, and oral administration of 30-45 mg of cevimeline three times daily increased unstimulated salivary flow.     

The impact of dose escalation on secondary cancer risk after radiotherapy of prostate cancer

PURPOSE: To estimate secondary cancer risk due to dose escalation in patients treated for prostatic carcinoma with three-dimensional conformal radiotherapy (3D-CRT), intensity-modulated RT (IMRT), and spot-scanned proton RT. METHODS AND MATERIALS: The organ equivalent dose (OED) concept with a linear-exponential, a plateau, and a linear dose-response curve was applied to dose distributions of 23 patients who received RT of prostate cancer. Conformal RT was used in 7 patients, 8 patients received IMRT with 6- and 15-MV photons, and 8 patients were treated with spot-scanned protons. We applied target doses ranging from 70 Gy to 100 Gy. Cancer risk was estimated as a function of target dose and tumor control probability. RESULTS: At a 100-Gy target dose the secondary cancer risk relative to the 3D treatment plan at 70 Gy was +18.4% (15.0% for a plateau model, 22.3% for a linear model) for the 6-MV IMRT plan, +25.3% (17.0%, 14.1%) for the 15-MV IMRT plan, and -40.7% (-41.3%, -40.0%) for the spot-scanned protons. The increasing risk of developing a radiation-associated malignancy after RT with increasing dose was balanced by the enhanced cure rates at a larger dose. CONCLUSIONS: Cancer risk after dose escalation for prostate RT is expected to be equal to or lower than for conventional 3D treatment at 70 Gy, independent of treatment modality or dose-response model. Spot-scanned protons are the treatment of choice for dose escalation because this therapy can halve the risk of secondary cancers.