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New research shows that limiting how pharmaceutical sales representatives can market their products to physicians changes their drug prescribing behaviors. A team, led by the University of California, Los Angeles' Ian Larkin and Carnegie Mellon University's George Loewenstein, examined restrictions 19 academic medical centers (AMCs) in five U.S. states placed on pharmaceutical representatives' visits to doctors' offices. Published in the May 2 issue of the Journal of the American Medical Association, the results reveal that the restrictions caused physicians to switch from prescribing drugs that were more expensive and patent-protected to generic, significantly cheaper drugs. Pharmaceutical sales representative visits to doctors, known as "detailing," is the most prominent form of pharmaceutical company marketing. Detailing often involves small gifts for physicians and their staff, such as meals. Pharmaceutical companies incur far greater expenditures on detailing visits than they do on direct-to-consumer marketing, or even on research and development of new drugs. Despite the prevalence of detailing and the numerous programs to regulate detailing, little was known about how practice-level detailing restrictions affect physician prescribing, until now. For the study, which is the largest, most comprehensive investigation into the impact of detailing restrictions, the team compared changes in the prescribing behavior of thousands of doctors before and after their AMCs introduced policies restricting detailing with the prescribing behavior of a carefully matched control group of similar physicians practicing in the same geographic regions but not subject to detailing restrictions. In total, the study included 25,000 physicians and 262 drugs in eight major drug classes from statins to sleep aids to antidepressants, representing more than $60 billion in aggregate sales in the U.S. "The study cannot definitively prove a causal link between policies that regulated detailing and changes in physician prescribing, but absent a randomized control, this evidence is as definitive as possible," said Larkin, assistant professor of strategy at UCLA's Anderson School of Management. "We investigated 19 different policy implementations that happened over a six-year period, included a control group of highly similar physicians not subject to detailing restrictions and looked at effects in eight large drug classes. The results were remarkable robust -- after the introduction of policies, about five to 10 percent of physician prescribing behavior changed." Specifically, the researchers found that detailing policies were associated with an 8.7 percent decrease in the market share of the average detailed drug. Before policy implementation, the average drug had a 19.3 percent market share. The findings also suggest that detailing may influence physicians in indirect ways. "No medical center completely barred salesperson visits; salespeople could and did continue to visit physicians at all medical centers in the study," Larkin said. "The most common restriction put in place was a ban on meals and other small gifts. The fact that regulating gifts while still allowing sales calls still led to a switch to cheaper, generic drugs may suggest that gifts such as meals play an important role in influencing physicians. The correlation between meals and prescribing has been well established in the literature, but our study suggests this relationship may be causal in nature." In light of these findings, the study indicates that physician practices and other governing bodies may need to take an active role in regulating conflicts of interest, rather than relying on individual physicians to monitor and regulate. "Social science has long demonstrated that professionals, even well-meaning ones, are powerfully influenced by conflicts of interest," said Loewenstein, the Herbert A. Simon University Professor of Economics and Psychology at CMU. "A large body of research also shows that simply disclosing conflicts of interests is insufficient to reduce their influence, and may even exacerbate it. The results from this study underline the effectiveness of, and need for, centralized rules and regulations. We should not put the onus of dealing with conflicts on patients; the best policies are those that eliminate conflicts." Larkin and Loewenstein also have a Viewpoint article in the same JAMA issue that calls for physicians to be compensated on a salary basis, instead of fee-for-service, to eliminate additional conflicts of interest. In addition to Larkin and Loewenstein, the research team included University of California, San Diego's Desmond Ang; Austrian Institute of Technology's Jonathan Steinhart; Williams College's Matthew Chao; Carnegie Mellon's Mark Patterson; Cornell University's Sunita Sah; New York University's Tina Wu; National Institute of Mental Health's Michael Schoenbaum; David Hutchins and Troyen Brennan from CVS Caremark. The National Institute of Mental Health provided funding, and CVS Caremark provided data, for the study.


Perez-Mitta G.,National University of La Plata | Tuninetti J.S.,National University of La Plata | Knoll W.,Austrian Institute of Technology GmbH | Trautmann C.,Helmholtz Center for Heavy Ion Research | And 2 more authors.
Journal of the American Chemical Society | Year: 2015

The ability to modulate the surface chemical characteristics of solid-state nanopores is of great interest as it provides the means to control the macroscopic response of nanofluidic devices. For instance, controlling surface charge and polarity of the pore walls is one of the most important applications of surface modification that is very relevant to attain accurate control over the transport of ions through the nanofluidic architecture. In this work, we describe a new integrative chemical approach to fabricate nanofluidic diodes based on the self-polymerization of dopamine (PDOPA) on asymmetric track-etched nanopores. Our results demonstrate that PDOPA coating is not only a simple and effective method to modify the inner surface of polymer nanopores fully compatible with the fabrication of nanofluidic devices but also a versatile platform for further integration of more complex molecules through different covalent chemistries and self-assembly processes. We adjusted the chemical modification strategy to obtain various configurations of the pore surface: (i) PDOPA layer was used as primer, precursor, or even responsive functional coating; (ii) PDOPA layer was used as a platform for anchoring chemical functions via the Michael addition reaction; and (iii) PDOPA was used as a reactive layer inducing the metallization of the pore walls through the in situ reduction of metallic precursors present in solution. We believe that the transversal concept of integrative surface chemistry offered by polydopamine in combination with the remarkable physical characteristics of asymmetric nanopores constitutes a new framework to design multifunctional nanofluidic devices employing soft chemistry-based nanofunctionalization techniques. (Graph Presented). © 2015 American Chemical Society.


News Article | November 16, 2016
Site: www.sciencedaily.com

The usual method of recording periodic leg movements in sleep for people with sleep disorders is to use electromyography (EMG), an electrophysiological method used in neurological diagnosis that measures muscle activity. However, the cables that this method requires can interfere with the patient's sleep and electrodes can become detached, thereby compromising the quality of the data. In a study led by MedUni Vienna's Department of Neurology, Austrian scientists have now demonstrated that superior data can be obtained using supplementary 3D scene analysis of movements, which is now being used for the first time. Under the direction of sleep researcher, Stefan Seidel, in collaboration with the Austrian Institute of Technology (AIT/project leader Heinrich Garn) MedUni Vienna experts have developed intelligent software that can record and analyse even more leg movements than conventional EMG, as well as being completely contactless. In this method, the 3D camera is installed directly above the bed. Other partners involved in the study were the Barmherzige Brüder Hospital in Vienna and Linz General Hospital. "This opens up new possibilities for us in the future, and not only for diagnosing and analysing sleep disorders," says Seidel. In future, 3D scene analysis could also be used to supplement the usual methods (EEG, ECG, EMG, nasal cannula) for monitoring epilepsy, sleep apnoea and sleep-walking, thereby enabling the causes to be analysed much more quickly than before. This opens up completely new options for home screening of patients, especially older people or young children. "On top of that, this form of analysis saves sleep researchers a great deal of time," explains Seidel. Periodic leg movements in sleep disrupt the night-time sleep of those affected, so that it is no longer restorative and they feel increasingly tired during the day. This is frequently due to Restless Legs Syndrome. Symptoms are treated by drugs such as dopamine antagonists, antiepileptic drugs or -- increasingly -- opiates.


Tajmar M.,Institute of Space Technology | Tajmar M.,KAIST | Vasiljevich I.,Institute of Space Technology | Grienauer W.,Austrian Institute of Technology GmbH
Ultramicroscopy | Year: 2010

We recently developed an indium Liquid-Metal-Ion-Source that can emit currents from sub-γA up to several mA. It is based on a porous tungsten crown structure with 28 individual emitters, which is manufactured using Micro-Powder Injection Molding (γPIM) and electrochemical etching. The emitter combines the advantages of internal capillary feeding with excellent emission properties due to micron-size tips. Significant progress was made on the homogeneity of the emission over its current-voltage characteristic as well as on investigating its long-term stability. This LMIS seems very suitable for space propulsion as well as for micro/nano manufacturing applications with greatly increased milling/drilling speeds. This paper summarizes the latest developments on our porous multiemitters with respect to manufacturing, emission properties and long-term testing. © 2010 Elsevier B.V.


Kral C.,Austrian Institute of Technology GmbH | Haumer A.,Technical Consulting and Electrical Engineering | Lee S.B.,Korea University
IEEE Transactions on Power Electronics | Year: 2014

A thermal model for the determination of the temperatures of interior permanent magnets and stator windings is presented in this paper. The innovation of the model relies on one temperature sensor being located in the stator core of the machine. Such sensor is simple to implement in many applications such as traction or EV, where reliability is critical. The estimated stator winding and permanent magnet temperatures are determined by a simplified thermal lumped element network model with only two time constants. It is shown that the proposed thermal model is very robust due to the structure of the model and the measured stator core temperature. The distortion of the temperature estimates caused by the cooling circuit is inherently accounted for such that the model can be used for robust online prediction of temperatures. Experimental results based on a forced water-cooled interior permanent magnet synchronous machine setup are presented to validate the effectiveness of the presented model. © 1986-2012 IEEE.


Hardoim P.R.,University of Algarve | Hardoim P.R.,Federal University of Rio de Janeiro | Van Overbeek L.S.,Plant Research International | Berg G.,University of Graz | And 5 more authors.
Microbiology and Molecular Biology Reviews | Year: 2015

All plants are inhabited internally by diverse microbial communities comprising bacterial, archaeal, fungal, and protistic taxa. These microorganisms showing endophytic lifestyles play crucial roles in plant development, growth, fitness, and diversification. The increasing awareness of and information on endophytes provide insight into the complexity of the plant microbiome. The nature of plant-endophyte interactions ranges from mutualism to pathogenicity. This depends on a set of abiotic and biotic factors, including the genotypes of plants and microbes, environmental conditions, and the dynamic network of interactions within the plant biome. In this review, we address the concept of endophytism, considering the latest insights into evolution, plant ecosystem functioning, and multipartite interactions. Copyright © 2015, American Society for Microbiology. All Rights Reserved.


Li J.,University of Helsinki | Brader G.,University of Helsinki | Helenius E.,University of Helsinki | Helenius E.,Austrian Institute of Technology GmbH | And 2 more authors.
Plant Journal | Year: 2012

In addition to its essential metabolic functions, biotin has been suggested to play a critical role in regulating gene expression. The first committed enzyme in biotin biosynthesis in Arabidopsis, 7-keto-8-aminopelargonic acid synthase, is encoded by At5g04620 (BIO4). We isolated a T-DNA insertion mutant of BIO4 (bio4-1) with a spontaneous cell death phenotype, which was rescued both by exogenous biotin and genetic complementation. The bio4-1 plants exhibited massive accumulation of hydrogen peroxide and constitutive up-regulation of a number of genes that are diagnostic for defense and reactive oxygen species signaling. The cell-death phenotype was independent of salicylic acid and jasmonate signaling. Interestingly, the observed increase in defense gene expression was not accompanied by enhanced resistance to bacterial pathogens, which may be explained by uncoupling of defense gene transcription from accumulation of the corresponding protein. Characterization of biotinylated protein profiles showed a substantial reduction of both chloroplastic biotinylated proteins and a nuclear biotinylated polypeptide in the mutant. Our results suggest that biotin deficiency results in light-dependent spontaneous cell death and modulates defense gene expression. The isolation and molecular characterization of the bio4-1 mutant provides a valuable tool for elucidating new functions of biotin. © 2011 Blackwell Publishing Ltd.


Simko M.,Austrian Academy of Sciences | Simko M.,Austrian Institute of Technology GmbH | Nosske D.,Federal office for Radiation Protection | Kreyling W.G.,Helmholtz Center for Environmental Research
International Journal of Environmental Research and Public Health | Year: 2014

In order to calculate the dose for nanoparticles (NP), (i) relevant information about the dose metrics and (ii) a proper dose concept are crucial. Since the appropriate metrics for NP toxicity are yet to be elaborated, a general dose calculation model for nanomaterials is not available. Here we propose how to develop a dose assessment model for NP in analogy to the radiation protection dose calculation, introducing the so-called "deposited and the equivalent dose". As a dose metric we propose the total deposited NP surface area (SA), which has been shown frequently to determine toxicological responses e.g. of lung tissue. The deposited NP dose is proportional to the total surface area of deposited NP per tissue mass, and takes into account primary and agglomerated NP. By using several weighting factors the equivalent dose additionally takes into account various physico-chemical properties of the NP which are influencing the biological responses. These weighting factors consider the specific surface area, the surface textures, the zeta-potential as a measure for surface charge, the particle morphology such as the shape and the length-to-diameter ratio (aspect ratio), the band gap energy levels of metal and metal oxide NP, and the particle dissolution rate. Furthermore, we discuss how these weighting factors influence the equivalent dose of the deposited NP. © 2014 by the authors; licensee MDPI, Basel, Switzerland.


Reitinger S.,Austrian Academy of Sciences | Wissenwasser J.,Austrian Institute of Technology GmbH | Kapferer W.,Austrian Academy of Sciences | Heer R.,Austrian Institute of Technology GmbH | Lepperdinger G.,Austrian Academy of Sciences
Biosensors and Bioelectronics | Year: 2012

Biosensor systems which enable impedance measurements on adherent cell layers under label-free conditions are considered powerful tools for monitoring specific biological characteristics. A radio frequency identification-based sensor platform was adopted to characterize cultivation and differentiation of human bone marrow-derived multipotent stem cells (bmMSC) over periods of up to several days and weeks. Electric cell-substrate impedance sensing was achieved through fabrication of sensitive elements onto glass substrates which comprised two comb-shaped interdigitated gold electrodes covering an area of 1.8 mm × 2. mm. The sensing systems were placed into the wells of a 6-well tissue culture plate, stacked onto a reader unit and could thus be handled and operated under sterile conditions. Continuous measurements were carried out with a sinusoidal voltage of 35. mV at a frequency of 10 kHz. After seeding of human bmMSC, this sensor was able to trace significant impedance changes contingent upon cell spreading and adhesion. The re-usable system was further proven suitable for live examination of cell-substrate attachment or continuous cell monitoring up to several weeks. Induction of either osteogenic or adipogenic differentiation could be validated in bmMSC cultures within a few days, in contrast to state-of-the-art protocols, which require several weeks of cultivation time. In the context of medical cell production in a GMP-compliant process, the here presented interdigitated electric microsensor technology allows the documentation of MSC quality in a fast, efficient and reliable fashion. © 2012 Elsevier B.V.


Sauer U.,Austrian Institute of Technology GmbH | Pultar J.,Austrian Institute of Technology GmbH | Preininger C.,Austrian Institute of Technology GmbH
Journal of Immunological Methods | Year: 2012

Both highly specific antibodies and appropriate assay buffers are key elements in the development of sensitive multi-analyte diagnostic tests and essential assay components to minimize interferences from the sample matrix.Herein, we investigate the influence of 0.1M Tris (pH 7.4)/0.1M NaCl/10mM CaCl 2/0.1% Tween-20 used as assay buffer and diluent for serum, plasma and saliva samples in a protein biomarker chip for the diagnosis of sepsis. In detail, on-chip sandwich assays for detection of IL-6 and PCT are established using pure assay buffer and serum, plasma, and saliva, each diluted by a factor of 10 and 100 with assay buffer. The dilution linearity as well as the cross-reactivity to immobilized IL-8, IL-10 and TNF-α antibodies (<1.8% in plasma and serum) is investigated; furthermore the influence of immunoglobulin G, fibrinogen and lysozyme, highly abundant proteins in serum, plasma and saliva. This effect is two times more pronounced in serum than in plasma and saliva and strongly decreases with increasing analyte concentration. Though the matrix proteins bind unspecifically to the immobilized receptors, they do not prevent the analyte binding; on the contrary, the analyte is reliably detected with high sensitivity, featuring limits of detection of 16ng/L and 0.31μg/L, and coefficients of variation of 18% and 29% for IL-6 and PCT in 10% serum. © 2012 Elsevier B.V.

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