1,205 research outputs found
Selbstregulierung und Fremdsteuerung in Medienkommunikation sowie subjektiver und sozialer Medienaneignung
No full textSutter T. Selbstregulierung und Fremdsteuerung in Medienkommunikation sowie subjektiver und sozialer Medienaneignung. In: Allmendinger J, ed. Entstaatlichung und soziale Sicherheit. Verhandlungen des 31. Kongresses der Deutschen Gesellschaft für Soziologie in Leipzig 2002. Verhandlungen des .. Kongresses der Deutschen Gesellschaft für Soziologie. Vol 31. Opladen: Leske + Budrich; 2003
Rheological investigation of manufacturability and injectability of highly concentrated monoclonal antibody formulations
No full textHighly concentrated protein therapeutics offer a convenient way for subcutaneous (sc) drug administration by the patient him-/herself or a healthcare professional. As the therapy e.g. with monoclonal antibodies requires quite high doses in the range of mg per kg body weight, the development of highly concentrated protein formulations is needed due to the limited injection volume, generally considered being 1 - 2 mL for sc administration. The development of highly concentrated formulations exceeding 50 - 100 mg/mL poses several challenges including chemical and physical stability (e.g. aggregation) as well as solution viscosity. Thereby, the increase in viscosity observed with higher protein concentration may cause severe limitations during product development as well as processing and drug administration. These limitations are defined by the flow rate/injection rate depending on the applied pressure which is needed during manufacture (fill-finish), in particular during filtration, and drug administration.
The focus of this work was to investigate the rheological behavior of protein solutions at high protein concentrations. The main objective was to obtain a profound understanding of two critical, hydrodynamic processes for highly concentrated protein solutions, which were drug administration and filtration, and to elucidate the role of viscosity with regard to potential limitations.
The current work provides a detailed overview on product characteristics of ten commercially available, highly concentrated protein therapeutics (Chapter 1). This technical overview summarizes formulation properties like viscosity and number of visible and sub-visible particles, physico-chemical properties like pH and osmolality as well as injection device characteristics, such as device dimensions. The analysis of marketed products revealed significant differences between the products. The current benchmark for maximum protein concentration and of viscosity was identified as a liquid formulation at a protein concentration of 200 mg/mL with a dynamic viscosity of 102 mPas (20? C). This product, which is provided in a pre-filled syringe, also exhibits the largest inner needle diameter of 25 G compared to other commercial products using 27 G needle for the injection device.
In the following (Chapter 2), advantages and limitations of different methods for viscosity determination of protein formulations are discussed. Moreover, a high-throughput method to measure viscosity was established. This method uses a capillary electrophoresis instrumentation without operation of the electrical field. The established method has the advantage of being automated offering the possibility for high-throughput by use of low sample amounts in the microliter range at the same time. (Allmendinger et al., J Pharm Biomed Anal, 99 (2014) 51-58)
Based on these studies, the present work investigated and characterized the subcutaneous drug administration process of highly concentrated protein formulations providing quantitative in vitro (Chapter 3) and in vivo data (G¨ottingen minipigs) of injection forces (Chapter 4).
Chapter 3 describes in detail the establishment of an in silico model to predict injection forces depending on syringe and needle dimensions, solution viscosity, and injection rate. Importantly, this model accounts for shear thinning behavior (non-Newtonian flow behavior) of highly concentrated protein olutions, which leads to lower effective injection forces than expected from current literature models. (Allmendinger et al., Eu J Pharm Biopharm, 87 (2014) 318-328)
To address the in vivo situation, Chapter 4 investigates and quantifies the contribution of the subcutaneous tissue backpressure and specifically reports the additional influence of body temperature on injection forces, which was found to compensate the tissue backpressure to some parts. Overall, an extended model, which addresses the injection force as a function of viscosity, volumetric flow/injection rate, needle/device dimensions, shear-thinning behavior, sc backpressure, and body temperature, was developed to predict injection forces representative for the in vivo situation. This knowledge is of key importance for the development of combination products (e.g. autoinjectors or pre-filled syringes) as a detailed understanding of injection forces depending on various parameters is required. It may be also supportive for the definition of limits during the evaluation, planning, and design phase during the development of injection devices. (Allmendinger et al., submitted to Pharm Research, 2014)
Besides drug administration, filtration was investigated as another critical hydrodynamic process for highly concentrated protein formulations, depending on formulation composition and filter material (Chapter 5). For both processes, filtration and drug administration, shear thinning behavior was found for some of the products depending on viscosity and protein concentration, shear rate, and formulation composition.
Within the present work it was shown, that the two investigated hydrodynamic processes, filtration and drug administration by injection, are two highly complex processes which are influenced by various factors. Thereby, the final limiting parameter for the injection process is given by the user capability of the patient population. However, the needle inner diameter was shown to have major influence on injection forces. It is related to injection forces by the power of four compared to other parameters like viscosity, injection rate, and contribution of sc backpressure being directly proportional. For the filtration process, the final limiting parameter may be discussed controversially. The study showed that the filtration pressure is mainly defined by the pore size distribution of the filter material, which was furthermore found to trigger the rheological behavior at high protein concentrations dependent on filtration rate. Moreover, literature data reported that the influence of filtration pressure on product quality might not be the limiting parameter during filtration. For the formulations previously tested, the shear stress exposure during manufacture was not considered important for final product quality, however only tested up to a protein concentration of 100 mg/mL. More important causes of aggregation were suggested to be the presence of air-bubbles, adsorption to solid surfaces, or contamination by particulates. Nevertheless, the stability of formulations showing pronounced shear-thinning behavior at high shear rates, which is most likely only the case for higher protein concentrations than previously tested, needs further experiments and has to be evaluated on a case-by-case basis dependent on product and process characteristics. (Allmendinger et al., submitted to J Pharm Sci, 2014)
With respect to viscosity, the current work has demonstrated for both processes, drug administration and filtration, that the potential limitation defined by the proportional increase in pressure based on Newtonian flow behavior was overestimated due to the presence of shear-thinning behavior which was shown for highly concentrated protein formulations
Change, Rigidity & Delay in the UK System of Land-use Development Control
No full textThe British system of development control is time-consuming and uncertain in outcome. Moreover, it is becoming increasingly overloaded as it has gradually switched away from being centred on a traditional ‘is it an appropriate land-use?’ type approach to one based on multi-faceted inspections of projects and negotiations over the distribution of the potential financial gains arising from them. Recent policy developments have centred on improving the operation of development control. This paper argues that more fundamental issues may be a stake as well. Important market changes have increased workloads. Furthermore, the UK planning system's institutional framework encourages change to move in specific directions, which is not always helpful. If expectations of increased long-term housing supply are to be met more substantial changes to development control may be essential but hard to achieve.
Contact-Heat Evoked Potentials: Insights into Pain Processing in CRPS Type I
No full textFlorin Allmendinger,1 Paulina Simonne Scheuren,1– 4 Iara De Schoenmacker,1 Florian Brunner,5 Jan Rosner,1,2,6 Armin Curt,1 Michèle Hubli1 1Spinal Cord Injury Center, Balgrist University Hospital, University of Zurich, Zurich, Switzerland; 2Department of Neurology, University Hospital Bern, Inselspital, University of Bern, Bern, Switzerland; 3International Collaboration on Repair Discoveries, Vancouver, BC, Canada; 4Department of Anesthesiology, Pharmacology & Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada; 5Department of Physical Medicine and Rheumatology, Balgrist University Hospital, University of Zurich, Zurich, Switzerland; 6Danish Pain Research Center, Department of Clinical Medicine, Aarhus University, Aarhus, DenmarkCorrespondence: Florin Allmendinger, Spinal Cord Injury Center, Balgrist University Hospital, University of Zurich, Forchstrasse 340, Zurich, CH-8008, Switzerland, Tel +41 44 510 72 11, Email [email protected]: The pathophysiological mechanisms underlying the development of chronic pain in complex regional pain syndrome (CRPS) are diverse and involve both peripheral and central changes in pain processing, such as sensitization of the nociceptive system. The aim of this study was to objectively distinguish the specific changes occurring at both peripheral and central levels in nociceptive processing in individuals with chronic CRPS type I.Patients and Methods: Nineteen individuals with chronic CRPS type I and 16 age- and sex-matched healthy controls (HC) were recruited. All individuals underwent a clinical examination and pain assessment in the most painful limb, the contralateral limb, and a pain-free control area to distinguish between peripheral and central mechanisms. Contact-heat evoked potentials (CHEPs) were recorded after heat stimulation of the three different areas and amplitudes and latencies were analyzed. Additionally, quantitative sensory testing (QST) was performed in all three areas.Results: Compared to HC, CHEP amplitudes in CRPS were only increased after stimulation of the painful area (p=0.025), while no increases were observed for the pain-free control area (p=0.14). None of the CHEP latencies were different between the two cohorts (all p> 0.23). Furthermore, individuals with CRPS showed higher pain ratings after stimulation of the painful limb compared to their contralateral limb (p=0.013). Lastly, compared to HC, mechanical (p=0.012) and thermal (p=0.046) sensitivity was higher in the painful area of the CRPS cohort.Conclusion: This study provides neurophysiological evidence supporting an intact thermo-nociceptive pathway with signs of peripheral sensitization, such as hyperexcitable primary afferent nociceptors, in individuals with CRPS type I. This is further supported by the observation of mechanical and thermal gain of sensation only in the painful limb. Additionally, the increased CHEP amplitudes might be related to fear-induced alterations of nociceptive processing.Keywords: sensitization, thermo-nociceptive processing, pain mechanism, pain hypersensitivity, complex regional pain syndrome, contact-heat evoked potential
The UK’s first professional symphony orchestra cooperative: social enterprise?
No full textThis conference paper reports the results of the first phase of a three phase longitudinal research study designed to examine the initiation and development of the UK‟s first professional symphony orchestra cooperative. Semi-structured interviews were conducted with thirty six professional musicians from a "pool" of forty plus musicians. This "pool" of musicians provides the cooperative with a resource that can be drawn on to form an orchestra to rehearse for and perform concerts and recordings. Preliminary results reveal four themes that emerged from the semi-structured interview data. These themes were interpreted by the researchers as: "commitment", "democracy", "social mission" and "aesthetic aspirations". The themes are presented along with supporting quotations from the interview data that illustrate the characteristics of these four emergent themes. The implications of the themes are then discussed within the context of the prior literature reviewe
1981 Challenges BJC--Page 80
No full textPhotographs of BJC studentsJeff Bullis
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We Can Only Say What a Basque Is Not
No full textWhat does it mean to be Basque, and why has this question become more complicated in the twenty-first century? An examination of several artists and their work provide possible answers to this question. American avant-garde artist Man Ray produced an experimental silent film in 1926 entitled Emak Bakia. Why he used this Basque phrase—which roughly translates as “Leave me alone”— is a mystery that has never been solved. In 2012, Basque filmmaker Oskar Alegria decided to track down the source of Ray’s inspiration in his documentary, The Search for Emak Bakia, 2012. By a strange twist of circumstance, searching for Alegria’s film turns out to be as difficult as solving the mystery of Emak Bakia. The film has never been shown in the United States, though a private copy was made available to the author of this article with the director’s permission. A Maurice Ravel musical composition and Eduardo Chillida’s sculpture in the Basque Country also help to explore this question. Together, the nuances of these collective artistic endeavors and their focus on “what is not” can suggest an alternative way to think about “what is.
Bibliographie
No full textAllmendinger J., (1989), « Educational Systems and Labour Market Outcomes », European Sociological Review, vol 5, n ° 3, p. 231-250. Auffray A. -F., (1929), Un grand éducateur, bienheureux Don Bosco (1815-1888), Lyon, Librairie Catholique Emmanuel Vitte. Arnaud L., Le bart C. & Pasquier R. (éd.), (2006), Idéologies et action publique territoriale, la politique change-t-elle encore le politique ?, Rennes, Presses Universitaires de Rennes. Audouin-Rouzeau S., (1989), 1870, la France en guerre, ..
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