Vertical Syndication-Proof Competitive Prices in Multilateral Markets

[eng] A multi-sided Böhm-Bawerk assignment game (Tejada, to appear) is a model for a multilateral market with a finite number of perfectly complementary indivisible commodities owned by different sellers, and inflexible demand and support functions. We show that for each such market game there is a unique vector of competitive prices for the commodities that is vertical syndication-proof, in the sense that, at those prices, syndication of sellers each owning a different commodity is neither beneficial nor detrimental for the buyers. Since, moreover, the benefits obtained by the agents at those prices correspond to the nucleolus of the market game, we provide a syndication-based foundation for the nucleolus as an appropriate solution concept for market games. For different solution concepts a syndicate can be disadvantageous and there is no escape to Aumman’s paradox (Aumann, 1973). We further show that vertical syndicationproofness and horizontal syndication-proofness – in which sellers of the same commodity collude – are incompatible requirements under some mild assumptions. Our results build on a self-interesting link between multi-sided Böhm-Bawerk assignment games and bankruptcy games (O’Neill, 1982). We identify a particular subset of Böhm-Bawerk assignment games and we show that it is isomorphic to the whole class of bankruptcy games. This isomorphism enables us to show the uniqueness of the vector of vertical syndication-proof prices for the whole class of Böhm-Bawerk assignment market using well-known results of bankruptcy problems.

Proof of concept for microarray-based detection of DNA-binding oncogenes in cell extracts.

The function of DNA-binding proteins is controlled not just by their abundance, but mainly at the level of their activity in terms of their interactions with DNA and protein targets. Moreover, the affinity of such transcription factors to their target sequences is often controlled by co-factors and/or modifications that are not easily assessed from biological samples. Here, we describe a scalable method for monitoring protein-DNA interactions on a microarray surface. This approach was designed to determine the DNA-binding activity of proteins in crude cell extracts, complementing conventional expression profiling arrays. Enzymatic labeling of DNA enables direct normalization of the protein binding to the microarray, allowing the estimation of relative binding affinities. Using DNA sequences covering a range of affinities, we show that the new microarray-based method yields binding strength estimates similar to low-throughput gel mobility-shift assays. The microarray is also of high sensitivity, as it allows the detection of a rare DNA-binding protein from breast cancer cells, the human tumor suppressor AP-2. This approach thus mediates precise and robust assessment of the activity of DNA-binding proteins and takes present DNA-binding assays to a high throughput level.

A novel in vitro metabolomics approach for neurotoxicity testing, proof of principle for methyl mercury chloride and caffeine

There is a need for more efficient methods giving insight into the complex mechanisms of neurotoxicity. Testing strategies including in vitro methods have been proposed to comply with this requirement. With the present study we aimed to develop a novel in vitro approach which mimics in vivo complexity, detects neurotoxicity comprehensively, and provides mechanistic insight. For this purpose we combined rat primary re-aggregating brain cell cultures with a mass spectrometry (MS)-based metabolomics approach. For the proof of principle we treated developing re-aggregating brain cell cultures for 48h with the neurotoxicant methyl mercury chloride (0.1-100muM) and the brain stimulant caffeine (1-100muM) and acquired cellular metabolic profiles. To detect toxicant-induced metabolic alterations the profiles were analysed using commercial software which revealed patterns in the multi-parametric dataset by principal component analyses (PCA), and recognised the most significantly altered metabolites. PCA revealed concentration-dependent cluster formations for methyl mercury chloride (0.1-1muM), and treatment-dependent cluster formations for caffeine (1-100muM) at sub-cytotoxic concentrations. Four relevant metabolites responsible for the concentration-dependent alterations following methyl mercury chloride treatment could be identified using MS-MS fragmentation analysis. These were gamma-aminobutyric acid, choline, glutamine, creatine and spermine. Their respective mass ion intensities demonstrated metabolic alterations in line with the literature and suggest that the metabolites could be biomarkers for mechanisms of neurotoxicity or neuroprotection. In addition, we evaluated whether the approach could identify neurotoxic potential by testing eight compounds which have target organ toxicity in the liver, kidney or brain at sub-cytotoxic concentrations. PCA revealed cluster formations largely dependent on target organ toxicity indicating possible potential for the development of a neurotoxicity prediction model. With such results it could be useful to perform a validation study to determine the reliability, relevance and applicability of this approach to neurotoxicity screening. Thus, for the first time we show the benefits and utility of in vitro metabolomics to comprehensively detect neurotoxicity and to discover new biomarkers.

Traitements de fer: preuves de t'efficacité et bonne pratique clinique [Iron therapy: proof of efficacy and good clinical practice].

Efficacy of iron therapy, whether oral or intravenous, on biological markers of body iron stores is well recognized in medical literature, but current studies are heterogeneous, of sometimes dubious quality, and rarely address clinical outcomes. Precise practical guidelines appear available only for indications related to kidney disease. First-line intravenous use is reserved for situations comprising chronic renal failure, or patients presenting with malabsorption syndromes such as in inflammatory bowel disease. In all other situations, because of the non-negligible risk of hypersensitivity reactions, intravenous iron use is considered justified only in clinically sustained indications, for patients in whom oral administration of iron is unsatisfactory or impossible.

Proof of Concept: Examining Characteristics of Roadway Infrastructure in Various 3D Visualization Modes, 2015

Utilizing enhanced visualization in transportation planning and design gained popularity in the last decade. This work aimed at demonstrating the concept of utilizing a highly immersive, virtual reality simulation engine for creating dynamic, interactive, full-scale, three-dimensional (3D) models of highway infrastructure. For this project, the highway infrastructure element chosen was a two-way, stop-controlled intersection (TWSCI). VirtuTrace, a virtual reality simulation engine developed by the principal investigator, was used to construct the dynamic 3D model of the TWSCI. The model was implemented in C6, which is Iowa State University’s Cave Automatic Virtual Environment (CAVE). Representatives from the Institute of Transportation at Iowa State University, as well as representatives from the Iowa Department of Transportation, experienced the simulated TWSCI. The two teams identified verbally the significant potential that the approach introduces for the application of next-generation simulated environments to road design and safety evaluation.

Can resistance to trastuzumab be reversed by endocrine therapy? Combination of trastuzumab and letrozole after resistance to sequential trastuzumab and aromatase inhibitor monotherapies in patients with ER-positive, HER-2 positive, advanced breast cancer: a proof-of-concept trial (SAKK 23/03)

Introduction: Trastuzumab (T) is a cornerstone in the treatment of patients with HER2-overexpressing advanced breast cancer and development of resistance to T is a major therapeutic problem. HER-2 is part of a highly interactive signaling network that may impair efficacy of endocrine therapy. A sequential treatment design was chosen in this trial to ensure complete resistance to single agent therapy before receiving both a non-steroidal aromatase inhibitor (AI) and T. Any kind of clinical activity with combined treatment of AI and T after progression of single agent treatments could indicate restoration of sensitivity as a consequence of cross-talking and networking between both pathways. Methods: Key eligibility criteria included postmenopausal patients (pts.) with advanced, measurable, HER-2 positive (assessed by FISH, ratio (≥2)), HR positive disease and progression on prior treatment with a non-steroidal AI, e.g. letrozole or anastrozole, either in an adjuvant or advanced setting. Pts. received standard dose T monotherapy either weekly or three-weekly in step 1 and upon disease progression, continued T in combination with letrozole in step 2. The primary endpoint was clinical benefit response (CBR: CR, PR or SD for at least 24 weeks (+/- 1 week) according to RECIST) in step 2. Results: Thirteen pts. were enrolled in five centers in Switzerland. In step 1, six pts. (46%) achieved CBR. Median time to progression (TTP) was 161 days (Range: 50 - 627). Based on data collected until the end of May 2010, CBR was observed in seven out of the eleven evaluable pts. (64%) in step 2, including one pt. with partial response. Four of the seven pts. within step 2 that achieved CBR also had CBR in step 1. Seven out of eleven pts. have documented tumor progression during step 2 treatment. Median TTP for all eleven pts. was 184 days (range 61 - 471). Mean time on study treatment (TTP in step 1 plus TTP in step 2) for pts. reaching step 2 was 380 days (range 174 - 864). Adverse events were generally mild. Conclusion: Results of this proof-of-principle trial suggest that complete resistance to both AI and T can be overcome in a proportion of pts. by combined treatment of AI and T, as all pts. served as their own control. Our results appear promising for a new treatment strategy which offers a chemotherapy-free and well-tolerated option for at least a subset of the pts. with HR positive, HER-2 positive breast cancer. Further trials will need to corroborate this finding.

Single acquisition electrical property mapping based on relative coil sensitivities: A proof-of-concept demonstration.

PURPOSE: All methods presented to date to map both conductivity and permittivity rely on multiple acquisitions to compute quantitatively the magnitude of radiofrequency transmit fields, B1+. In this work, we propose a method to compute both conductivity and permittivity based solely on relative receive coil sensitivities ( B1-) that can be obtained in one single measurement without the need to neither explicitly perform transmit/receive phase separation nor make assumptions regarding those phases. THEORY AND METHODS: To demonstrate the validity and the noise sensitivity of our method we used electromagnetic finite differences simulations of a 16-channel transceiver array. To experimentally validate our methodology at 7 Tesla, multi compartment phantom data was acquired using a standard 32-channel receive coil system and two-dimensional (2D) and 3D gradient echo acquisition. The reconstructed electric properties were correlated to those measured using dielectric probes. RESULTS: The method was demonstrated both in simulations and in phantom data with correlations to both the modeled and bench measurements being close to identity. The noise properties were modeled and understood. CONCLUSION: The proposed methodology allows to quantitatively determine the electrical properties of a sample using any MR contrast, with the only constraint being the need to have 4 or more receive coils and high SNR. Magn Reson Med, 2014. © 2014 Wiley Periodicals, Inc.

Traumatic injuries after mechanical cardiopulmonary resuscitation (LUCAS?2): a forensic autopsy study.

AIM: The aim of our study was to compare traumatic injuries observed after cardiopulmonary resuscitation (CPR) by means of standard (manual) or assisted (mechanical) chest compression by Lund University Cardiopulmonary Assist System, 2nd generation (LUCAS?2) device. METHODS: A retrospective study was conducted including cases from 2011 to 2013, analysing consecutive autopsy reports in two groups of patients who underwent medicolegal autopsy after unsuccessful CPR. We focused on traumatic injuries from dermal to internal trauma, collecting data according to a standardised protocol. RESULTS: The study group was comprised of 26 cases, while 32 cases were included in the control group. Cardiopulmonary resuscitation performed by LUCAS?2 was longer than manual CPR performed in control cases (study group: mean duration 51.5 min; controls 29.4 min; p = 0.004). Anterior chest lesions (from bruises to abrasions) were described in 18/26 patients in the LUCAS?2 group and in 6/32 of the control group. A mean of 6.6 rib fractures per case was observed in the LUCAS?2 group, but this was only 3.1 in the control group (p = 0.007). Rib fractures were less frequently observed in younger patients. The frequency of sternal factures was similar in both groups. A few trauma injuries to internal organs (mainly cardiac, pulmonary and hepatic bruises), and some petechiae (study 46 %; control 41 %; p = 0.79) were recorded in both groups. CONCLUSION: LUCAS?2-CPR is associated with more rib fractures than standard CPR. Typical round concentric skin lesions were observed in cases of mechanical reanimation. No life-threatening injuries were reported. Petechiae were common findings.