[Verification of normative values for the Swiss version of the Freiburg speech intelligibility test.]

BACKGROUND AND OBJECTIVE: In the Swiss version of the Freiburg speech intelligibility test five test words from the original German recording which are rarely used in Switzerland have been exchanged. Furthermore, differences in the transfer functions between headphone and loudspeaker presentation are not taken into account during calibration. New settings for the levels of the individual test words in the recommended recording and small changes in calibration procedures led us to make a verification of the currently used normative values.PATIENTS AND METHODS: Speech intelligibility was measured in 20 subjects with normal hearing using monosyllabic words and numbers via headphones and loudspeakers.RESULTS: On average, 50% speech intelligibility was reached at levels which were 7.5 dB lower under free-field conditions than for headphone presentation. The average difference between numbers and monosyllabic words was found to be 9.6 dB, which is considerably lower than the 14 dB of the current normative curves.CONCLUSIONS: There is a good agreement between our measurements and the normative values for tests using monosyllabic words and headphones, but not for numbers or free-field measurements.

Squared Extrapolation Methods (SQUAREM): A New Class of Simple and Efficient Numerical Schemes for Accelerating the Convergence of the EM Algorithm

We derive a new class of iterative schemes for accelerating the convergence of the EM algorithm, by exploiting the connection between fixed point iterations and extrapolation methods. First, we present a general formulation of one-step iterative schemes, which are obtained by cycling with the extrapolation methods. We, then square the one-step schemes to obtain the new class of methods, which we call SQUAREM. Squaring a one-step iterative scheme is simply applying it twice within each cycle of the extrapolation method. Here we focus on the first order or rank-one extrapolation methods for two reasons, (1) simplicity, and (2) computational efficiency. In particular, we study two first order extrapolation methods, the reduced rank extrapolation (RRE1) and minimal polynomial extrapolation (MPE1). The convergence of the new schemes, both one-step and squared, is non-monotonic with respect to the residual norm. The first order one-step and SQUAREM schemes are linearly convergent, like the EM algorithm but they have a faster rate of convergence. We demonstrate, through five different examples, the effectiveness of the first order SQUAREM schemes, SqRRE1 and SqMPE1, in accelerating the EM algorithm. The SQUAREM schemes are also shown to be vastly superior to their one-step counterparts, RRE1 and MPE1, in terms of computational efficiency. The proposed extrapolation schemes can fail due to the numerical problems of stagnation and near breakdown. We have developed a new hybrid iterative scheme that combines the RRE1 and MPE1 schemes in such a manner that it overcomes both stagnation and near breakdown. The squared first order hybrid scheme, SqHyb1, emerges as the iterative scheme of choice based on our numerical experiments. It combines the fast convergence of the SqMPE1, while avoiding near breakdowns, with the stability of SqRRE1, while avoiding stagnations. The SQUAREM methods can be incorporated very easily into an existing EM algorithm. They only require the basic EM step for their implementation and do not require any other auxiliary quantities such as the complete data log likelihood, and its gradient or hessian. They are an attractive option in problems with a very large number of parameters, and in problems where the statistical model is complex, the EM algorithm is slow and each EM step is computationally demanding.

A Faster Circular Binary Segmentation Algorithm for the Analysis of Array CGH Data

Motivation: Array CGH technologies enable the simultaneous measurement of DNA copy number for thousands of sites on a genome. We developed the circular binary segmentation (CBS) algorithm to divide the genome into regions of equal copy number (Olshen {\it et~al}, 2004). The algorithm tests for change-points using a maximal $t$-statistic with a permutation reference distribution to obtain the corresponding $p$-value. The number of computations required for the maximal test statistic is $O(N^2),$ where $N$ is the number of markers. This makes the full permutation approach computationally prohibitive for the newer arrays that contain tens of thousands markers and highlights the need for a faster. algorithm. Results: We present a hybrid approach to obtain the $p$-value of the test statistic in linear time. We also introduce a rule for stopping early when there is strong evidence for the presence of a change. We show through simulations that the hybrid approach provides a substantial gain in speed with only a negligible loss in accuracy and that the stopping rule further increases speed. We also present the analysis of array CGH data from a breast cancer cell line to show the impact of the new approaches on the analysis of real data. Availability: An R (R Development Core Team, 2006) version of the CBS algorithm has been implemented in the ``DNAcopy'' package of the Bioconductor project (Gentleman {\it et~al}, 2004). The proposed hybrid method for the $p$-value is available in version 1.2.1 or higher and the stopping rule for declaring a change early is available in version 1.5.1 or higher.

Model-based control of neuromuscular block using mivacurium: design and clinical verification

BACKGROUND: Short-acting agents for neuromuscular block (NMB) require frequent dosing adjustments for individual patient's needs. In this study, we verified a new closed-loop controller for mivacurium dosing in clinical trials. METHODS: Fifteen patients were studied. T1% measured with electromyography was used as input signal for the model-based controller. After induction of propofol/opiate anaesthesia, stabilization of baseline electromyography signal was awaited and a bolus of 0.3 mg kg-1 mivacurium was then administered to facilitate endotracheal intubation. Closed-loop infusion was started thereafter, targeting a neuromuscular block of 90%. Setpoint deviation, the number of manual interventions and surgeon's complaints were recorded. Drug use and its variability between and within patients were evaluated. RESULTS: Median time of closed-loop control for the 11 patients included in the data processing was 135 [89-336] min (median [range]). Four patients had to be excluded because of sensor problems. Mean absolute deviation from setpoint was 1.8 +/- 0.9 T1%. Neither manual interventions nor complaints from the surgeons were recorded. Mean necessary mivacurium infusion rate was 7.0 +/- 2.2 microg kg-1 min-1. Intrapatient variability of mean infusion rates over 30-min interval showed high differences up to a factor of 1.8 between highest and lowest requirement in the same patient. CONCLUSIONS: Neuromuscular block can precisely be controlled with mivacurium using our model-based controller. The amount of mivacurium needed to maintain T1% at defined constant levels differed largely between and within patients. Closed-loop control seems therefore advantageous to automatically maintain neuromuscular block at constant levels.

[Acute lower gastrointestinal bleeding--an evidence-based algorithm for diagnosis and treatment]

Novel means to locate and treat lower gastrointestinal bleeding (lGB) allow to reduce the rate of required surgical interventions and help to limit the extend of resection. The risk stratification of patients with lGB is the primary step of our recommended treatment algorithm. Accordingly, risk stratifying instruments, which are only partly validated up to now, are gaining significance in lGB. Whereas, gastro-duodenoscopy and colonoscopy prior to angiography or scintigraphy are established diagnostic tools, capsule enteroscopy offers a novel approach to hemodynamic stable patients with lGB that are difficult to localize. With its every increasing sensitivity, Angio-Computer Tomography is likely to replace scintigraphy and diagnostic angiography in the very near future. In addition, recent advances in superselective microembolisation have been shown to have the potential rendering surgical interventions in a majority of patients with acute lGB unnecessary. The extend of required surgical resection is largely dependent on the success to localize the bleeding source of prior diagnostics. Only if the source is identified, a limited segmental resection should be performed. Should surgery be required, we suggest to maintain the effort to localize the bleeding, either by prior laparoscopy and/or by intraoperative entero-colonoscopy. Eventually, if the source of bleeding remains unclear total colectomy with ileorectal anastomosis represents the procedure of choice in patients with acute lGB.

Collapsed cone convolution and analytical anisotropic algorithm dose calculations compared to VMC++ Monte Carlo simulations in clinical cases

The purpose of this work was to study and quantify the differences in dose distributions computed with some of the newest dose calculation algorithms available in commercial planning systems. The study was done for clinical cases originally calculated with pencil beam convolution (PBC) where large density inhomogeneities were present. Three other dose algorithms were used: a pencil beam like algorithm, the anisotropic analytic algorithm (AAA), a convolution superposition algorithm, collapsed cone convolution (CCC), and a Monte Carlo program, voxel Monte Carlo (VMC++). The dose calculation algorithms were compared under static field irradiations at 6 MV and 15 MV using multileaf collimators and hard wedges where necessary. Five clinical cases were studied: three lung and two breast cases. We found that, in terms of accuracy, the CCC algorithm performed better overall than AAA compared to VMC++, but AAA remains an attractive option for routine use in the clinic due to its short computation times. Dose differences between the different algorithms and VMC++ for the median value of the planning target volume (PTV) were typically 0.4% (range: 0.0 to 1.4%) in the lung and -1.3% (range: -2.1 to -0.6%) in the breast for the few cases we analysed. As expected, PTV coverage and dose homogeneity turned out to be more critical in the lung than in the breast cases with respect to the accuracy of the dose calculation. This was observed in the dose volume histograms obtained from the Monte Carlo simulations.

Introduction of a novel dose saving acquisition mode for the PortalVision aS500 EPID to facilitate on-line patient setup verification

In external beam radiotherapy, electronic portal imaging becomes more and more an indispensable tool for the verification of the patient setup. For the safe clinical introduction of high dose conformal radiotherapy like intensity modulated radiation therapy, on-line patient setup verification is a prerequisite to ensure that the planned dosimetric coverage of the tumor volume is actually realized in the patient. Since the direction of setup fields often deviates from the direction of the treatment beams, extra dose is delivered to the patient during the acquisition of these portal images which may reach clinical relevance. The aim of this work was to develop a new acquisition mode for the PortalVision aS500 electronic portal imaging device from Varian Medical Systems that allows one to take portal images with reduced dose while keeping good image quality. The new acquisition mode, called RadMode, selectively enables and disables beam pulses during image acquisition allowing one to stop wasting valuable dose during the initial acquisition of "reset frames." Images of excellent quality can be taken with 1 MU only. This low dose per image facilitates daily setup verification with considerably reduced extra dose.

Application and assessment of a robust elastic motion correction algorithm to dynamic MRI

The purpose of this study was to assess the performance of a new motion correction algorithm. Twenty-five dynamic MR mammography (MRM) data sets and 25 contrast-enhanced three-dimensional peripheral MR angiographic (MRA) data sets which were affected by patient motion of varying severeness were selected retrospectively from routine examinations. Anonymized data were registered by a new experimental elastic motion correction algorithm. The algorithm works by computing a similarity measure for the two volumes that takes into account expected signal changes due to the presence of a contrast agent while penalizing other signal changes caused by patient motion. A conjugate gradient method is used to find the best possible set of motion parameters that maximizes the similarity measures across the entire volume. Images before and after correction were visually evaluated and scored by experienced radiologists with respect to reduction of motion, improvement of image quality, disappearance of existing lesions or creation of artifactual lesions. It was found that the correction improves image quality (76% for MRM and 96% for MRA) and diagnosability (60% for MRM and 96% for MRA).