Measurement-Based Modal Beamforming Using Planar Circular Microphone Arrays

This paper describes how to use a planar circular pressure-zone table-top microphone array for modal beamforming. Its goals are similar as for spherical arrays: higher-order resolution and a more-or-less steering-invariant beampattern design in the three-dimensional half space. As conventional circular arrays lack control of the beampattern in the vertical array plane, the proposed arrangement tries to fix this shortcoming to allow both horizontal and vertical control of beamforming. To provide a fully calibrated decomposition into the directional modes, the proposed beamforming approach is based on measurement data. From a MIMO (multiple-input-multiple-output) system description of the measurement data in the spherical harmonics domain, an inverse MIMO system of filters is designed for decomposing the microphone array signals into those spherical components eligible for modal beamforming. For an efficient measurement and robust set of decomposition filters, a reduced set of measurement positions and a regularisation strategy is suggested

Ambisonics

This open access book provides a concise explanation of the fundamentals and background of the surround sound recording and playback technology Ambisonics. It equips readers with the psychoacoustical, signal processing, acoustical, and mathematical knowledge needed to understand the inner workings of modern processing utilities, special equipment for recording, manipulation, and reproduction in the higher-order Ambisonic format. The book comes with various practical examples based on free software tools and open scientific data for reproducible research. The book’s introductory section offers a perspective on Ambisonics spanning from the origins of coincident recordings in the 1930s to the Ambisonic concepts of the 1970s, as well as classical ways of applying Ambisonics in first-order coincident sound scene recording and reproduction that have been practiced since the 1980s. As, from time to time, the underlying mathematics become quite involved, but should be comprehensive without sacrificing readability, the book includes an extensive mathematical appendix. The book offers readers a deeper understanding of Ambisonic technologies, and will especially benefit scientists, audio-system and audio-recording engineers. In the advanced sections of the book, fundamentals and modern techniques as higher-order Ambisonic decoding, 3D audio effects, and higher-order recording are explained. Those techniques are shown to be suitable to supply audience areas ranging from studio-sized to hundreds of listeners, or headphone-based playback, regardless whether it is live, interactive, or studio-produced 3D audio material

Efficient Phantom Source Widening and Diffuseness in Ambisonics

Object-based spatial audio considers virtual sound sources having a width/diffuseness parameter. This parameter aims at controlling the perceived width or diffuseness of the auditory object, or phantom source, created by the renderer. Width/diffuseness provides an important salience parameter that is independent of perceived direction and timbre. A highly efficient sparse filter structure for two-channel stereophony was described and tested recently, but it becomes ineffective for most parts of a large audience. This paper presents phantom source width/diffuseness control for Ambisonics. The new approach is a remarkably elegant application of the previously described stereo phantom source widening on Ambisonics. Compared with former experimental data, our experiments show a greater freedom of increasing the width and widening that works for a larger listening area

Sweet area size for the envelopment of a recursive and a non-recursive diffuseness rendering approach

We compare the extent of the usable audience area of two algorithms that produce diffusely enveloping, multi-channel surround playback from a single-channel input. The FIR approach designs a set of random group-delay allpass filters to generate a set of minimally correlated playback signals. Canfield-Dafilou presented a frequency-dependent maximum group delay value as a constraint to keep audible artifacts small, in studio environments. To enlarge the audience area in which an enveloping and diffuse listening experience is achieved, we relax this constraint while having to accept an unavoidable impression of spaciousness and reverberation. Consequently, the FIR approach naturally competes with IIR feedback-delay network as alternative approach. We conduct listening experiments to reveal quality and effectiveness of both methods, in particular regarding sweet area size and sound quality

Accelerator Physics Code Web Repository

In the framework of the CARE HHH European Network, we have developed a web-based dynamic acceleratorphysics code repository. We describe the design, structure and contents of this repository, illustrate its usage, and discuss our future plans, with emphasis on code benchmarking

The international WAO/EAACI guideline for the management of hereditary angioedema – the 2017 revision and update

Abstract Hereditary Angioedema (HAE) is a rare and disabling disease. Early diagnosis and appropriate therapy are essential. This update and revision of the global guideline for HAE provides up-to-date consensus recommendations for the management of HAE. In the development of this update and revision of the guideline, an international expert panel reviewed the existing evidence and developed 20 recommendations that were discussed, finalized and consented during the guideline consensus conference in June 2016 in Vienna. The final version of this update and revision of the guideline incorporates the contributions of a board of expert reviewers and the endorsing societies. The goal of this guideline update and revision is to provide clinicians and their patients with guidance that will assist them in making rational decisions in the management of HAE with deficient C1-inhibitor (type 1) and HAE with dysfunctional C1-inhibitor (type 2). The key clinical questions covered by these recommendations are: 1) How should HAE-1/2 be defined and classified?, 2) How should HAE-1/2 be diagnosed?, 3) Should HAE-1/2 patients receive prophylactic and/or on-demand treatment and what treatment options should be used?, 4) Should HAE-1/2 management be different for special HAE-1/2 patient groups such as pregnant/lactating women or children?, and 5) Should HAE-1/2 management incorporate self-administration of therapies and patient support measures? This article is co-published with permission in Allergy and the World Allergy Organization Journal

LICC: L-BLP25 in patients with colorectal carcinoma after curative resection of hepatic metastases--a randomized, placebo-controlled, multicenter, multinational, double-blinded phase II trial

Background: 15-20% of all patients initially diagnosed with colorectal cancer develop metastatic disease and surgical resection remains the only potentially curative treatment available. Current 5-year survival following R0-resection of liver metastases is 28-39%, but recurrence eventually occurs in up to 70%. To date, adjuvant chemotherapy has not improved clinical outcomes significantly. The primary objective of the ongoing LICC trial (L-BLP25 In Colorectal Cancer) is to determine whether L-BLP25, an active cancer immunotherapy, extends recurrence-free survival (RFS) time over placebo in colorectal cancer patients following R0/R1 resection of hepatic metastases. L-BLP25 targets MUC1 glycoprotein, which is highly expressed in hepatic metastases from colorectal cancer. In a phase IIB trial, L-BLP25 has shown acceptable tolerability and a trend towards longer survival in patients with stage IIIB locoregional NSCLC. Methods: This is a multinational, phase II, multicenter, randomized, double-blind, placebo-controlled trial with a sample size of 159 patients from 20 centers in 3 countries. Patients with stage IV colorectal adenocarcinoma limited to liver metastases are included. Following curative-intent complete resection of the primary tumor and of all synchronous/metachronous metastases, eligible patients are randomized 2:1 to receive either L-BLP25 or placebo. Those allocated to L-BLP25 receive a single dose of 300 mg/m2 cyclophosphamide (CP) 3 days before first L-BLP25 dose, then primary treatment with s.c. L-BLP25 930 mug once weekly for 8 weeks, followed by s.c. L-BLP25 930 mug maintenance doses at 6-week (years 1&2) and 12-week (year 3) intervals unless recurrence occurs. In the control arm, CP is replaced by saline solution and L-BLP25 by placebo. Primary endpoint is the comparison of recurrence-free survival (RFS) time between groups. Secondary endpoints are overall survival (OS) time, safety, tolerability, RFS/OS in MUC-1 positive cancers. Exploratory immune response analyses are planned. The primary endpoint will be assessed in Q3 2016. Follow-up will end Q3 2017. Interim analyses are not planned. Discussion: The design and implementation of such a vaccination study in colorectal cancer is feasible. The study will provide recurrence-free and overall survival rates of groups in an unbiased fashion. Trial Registration EudraCT Number 2011-000218-2

Frequency of the virilising effects of attenuated androgens reported by women with hereditary angioedema.

BACKGROUND: Danazol, a drug extensively used in the management of hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE), has various side effects. This study investigated the virilizing actions of this drug in 31 danazol-treated female patients with HAE-C1-INH. We compared our findings with those of healthy controls and with literature data. METHODS: The patients were interviewed individually about the type and severity of the virilizing effects, as well as about their satisfaction with danazol therapy. RESULTS: The average duration of danazol treatment was 10.31 years [2 to 23] and its mean daily dose was 131.7 mg [33 to 200]. The most common adverse effects were hirsutism (n = 14), weight gain (n = 13), and menstrual disturbances (n = 8). The severity of danazol adverse effects did not differ by duration of treatment or by daily drug dose. The mean level of patient satisfaction with the treatment was high. The comparison of age-matched healthy controls and of HAE-C1-INH patients receiving danazol did not demonstrate a statistically higher incidence of any of the monitored symptoms in the danazol group. CONCLUSIONS: Our findings indicate that long-term danazol treatment – using the lowest effective dose – has only a mild virilizing effect

Rise and Fall of an Anti-MUC1 Specific Antibody

So far, human antibodies with good affinity and specificity for MUC1, a transmembrane protein overexpressed on breast cancers and ovarian carcinomas, and thus a promising target for therapy, were very difficult to generate.A human scFv antibody was isolated from an immune library derived from breast cancer patients immunised with MUC1. The anti-MUC1 scFv reacted with tumour cells in more than 80% of 228 tissue sections of mamma carcinoma samples, while showing very low reactivity with a large panel of non-tumour tissues. By mutagenesis and phage display, affinity of scFvs was increased up to 500fold to 5,7×10(-10) M. Half-life in serum was improved from below 1 day to more than 4 weeks and was correlated with the dimerisation tendency of the individual scFvs. The scFv bound to T47D and MCF-7 mammalian cancer cell lines were recloned into the scFv-Fc and IgG format resulting in decrease of affinity of one binder. The IgG variants with the highest affinity were tested in mouse xenograft models using MCF-7 and OVCAR tumour cells. However, the experiments showed no significant decrease in tumour growth or increase in the survival rates. To study the reasons for the failure of the xenograft experiments, ADCC was analysed in vitro using MCF-7 and OVCAR3 target cells, revealing a low ADCC, possibly due to internalisation, as detected for MCF-7 cells.Antibody phage display starting with immune libraries and followed by affinity maturation is a powerful strategy to generate high affinity human antibodies to difficult targets, in this case shown by the creation of a highly specific antibody with subnanomolar affinity to a very small epitope consisting of four amino acids. Despite these "best in class" binding parameters, the therapeutic success of this antibody was prevented by the target biology

Efficient Phantom Source Widening

We present a highly efficient filter structure to create power-complementary filter pairs for phantom source widening. It either introduces frequency-dependent phase or amplitude differences in a pair of loudspeaker signals. We evaluate how the perceptual effect is influenced by off-center listening positions in a standard ±30o loudspeaker setup. The evaluation of the phantom source widening effect is based on measurements of the inter-aural cross-correlation coefficient (IACC), which is justified by its pronounced correlation to the perceived phantom source width in prior listening test results