A Sourcing Strategy for Active Pharmaceutical Ingredients (APIs)

We describe the development over the past decade of a sourcing strategy within the Roche group for active pharmaceutical ingredients and the intermediates used in their manufacture. The roles of certain production sites have been modified in the light of this strategy. Before sourcing decisions are taken, criteria including life-cycle phase of the product, whether the step under review comes early or late in the synthesis, protection of proprietary know-how, quantities needed, speed, available capacity and full production costs are systematically evaluated on a case-by-case basis. For each sourcing decision, different scenarios are compared, in particular that of in-house vs. external production. In future, we envisage intensified competition both among Contract Manufacturing Organisations (CMOs) for business from large pharma concerns and among the large pharma concerns themselves for the capacity available from the CMOs. In consequence, the large pharma concerns will have to continually adapt their sourcing strategies to the changing environment and will have to have available flexible production plants and organisations if they wish to maintain a viable in-house alternative to contract manufacture

Equivalence classes for named function networking

Named Function Networking (NFN) is a generalization of Content-Centric Networking (CCN) and Named Data Networking (NDN). Beyond mere content retrieval, NFN enables to ask for results of computations. Names are not just content identifiers but λ-expressions that allow an arbitrary composition of function calls and data accesses. λ-expressions are pure and deterministic. In other words, they do not have side effects and they always yield the same result. Both properties together are known to as referential transparency. Referentially transparent functions can be evaluated individually no matter where and in what order, e.g. geographically distributed and concurrently. This simplifies the distribution of computations in a network, an attractive feature in times of rising needs for edge computing. However, NFN is affected by a lacking awareness for referentially opaque expressions that are characterized by having changing results or side effects, i.e. expressions that depend on outer conditions or modify outer states. The fundamental motivation of this thesis is to retrofit NFN with a clearer notion of referentially opaque expressions. They are indispensable not only to many common use cases such as e-mail and database applications, but also to network technologies such as software defined networking. We observed that many protocol decisions are based on expression matching, i.e. the search for equivalent expressions. Driven by this observation, this thesis explores possibilities to adapt the determination of equivalences in dependence of crucial expression properties such as their ability for aggregation, concurrent evaluation or permanently cacheable results. This exploration results in a comprehensive set of equivalence classes that is used for explicit attribution of expressions, leading to a system that is aware of the true nature of handled expressions. Moreover, we deliver a solution to support referentially opaque expressions and mutable states in an architecture that bases upon uniquely named and immutable data packets. Altogether, the findings condense to an extended execution model. It summarizes how the attribution of expressions with equivalence classes influences specific protocol decisions in order to support referentially transparent as well as referentially opaque expressions. We believe that our approach captivates due to its generality and extensibility. Equivalence classes depend upon universal properties. Therefore, our approach is not bound to a specific elaboration like NFN. We evaluate the applicability of our approach in a few application scenarios. Overall, the proposed solutions and concepts are an important contribution towards name-based distributed computations in information-centric networks

Bauern, BLN und Landschaftsqualität : was wird in den Schweizer Vorbildlandschaften gemacht?

Die Nutzungsansprüche an die Landschaft sind genauso vielfältig wie sie selbst. So ist sie sowohl Wohn-, Arbeits-, Erholungs-, Bewegungs-, Kultur- und Wirtschaftsraum. Für die Erfüllung dieser Funktionen ist eine gute Qualität der Landschaft notwendig. Diese gerät zunehmend durch Auswirkungen des demografischen und klimatischen Wandels unter Druck. Insbesondere die natürlichen Landschaften und ihre Funktionen sind durch die abnehmende Biodiversität bedroht. Die Kulturlandschaft ihrerseits verliert durch sich verändernde Flächen- und Bodennutzungen ihre Eigenheiten. Vor diesem Hintergrund entwickelte die Schweizer Politik in den letzten Jahrzehnten eine Vielzahl an Gesetzen und Instrumenten als Gegenmassnahme. Die vorliegende Arbeit untersuchte vier dieser Instrumente: das Landschaftskonzept Schweiz als behördenverbindliches Planungsinstrument, das Bundesinventar der Landschaften und Naturdenkmäler von nationaler Bedeutung als Instrument zur Inwertsetzung und Planungsgrundlage, die Landschaftsqualitätsbeiträge gemäss Direktzahlungsverordnung als Instrument zur Förderung und die Pärke von nationaler Bedeutung als Vorbildinstrument in Erhalt und Aufwertung von Landschaften. Dabei wurden die von den Instrumenten gestützten Qualitäten und Ziele sowie deren Synergiemöglichkeiten ermittelt. Zusätzlich wurde über eine Fallstudie der Schweizer Pärke deren Massnahmen zur Aufwertung der Landschaftsqualität gesammelt. Die Erkenntnisse wurden durch die Erfahrungen des Parc Ela und der UNESCO Biosphäre Entlebuch abgeglichen. Dies geschah durch Experteninterviews mit den Verantwortlichen im Bereich Natur und Landschaft der Parkorganisationen. Schlussendlich konnten als Resultat Handlungsempfehlungen für politische Akteure zur Aufwertung der Landschaftsqualität von Regionen und Gemeinden ohne Parkperimeter verfasst werden.The demand to use the landscape is as diverse as the landscape itself. The landscape is simultaneously a living-, work-, recovery-, movement-, cultural- and economic area. For the completion of these demands, a good quality is necessary. The pressure on the landscape is raising through the effects of demographic and climatic change. Especially, the natural landscapes and their functions are threatened by declining biodiversity. The cultural landscapes are losing their characteristics as a result of land use change. As a countermeasure, the swiss politicians have developed a variety of laws and instruments. This thesis analysed four of these instruments: the Swiss Landscape Concept as an authority binding planning instrument, the Landscape Quality Contributions according to the Direct Payment Regulation as a funding instrument and the Parks of national importance as a role model instrument of developing and funding the landscapes. In doing so, the qualities and aims based on these instruments were determined as well as their possible synergies. In addition, a case study of the Swiss Parks was made to collect their measures to increase the landscape quality. The conclusions were adjusted by the experiences of the responsible persons from the UNESCO Bioshpere Entlebuch and Parc Ela. This has taken place through expert interviews with the person in charge in the section nature and landscape. Finally, recommendations for political actors to increase the landscape quality of regions and municipalities without a park perimeter were drafted

Lobbying in der Kommission für Wirtschaft und Abgaben des Nationalrats : die Interessenbindungen der Kommissionsmitglieder und deren Einfluss auf den Gesetzgebungsprozess von 2003 bis 2017

Der Gesetzgebungsprozess der Schweiz sieht in allen politischen Phasen die Anhörung von Interessengruppen vor. Dies schafft ein Fundament für breit abgestützte Kompromisse und sichert die Mehrheitsfähigkeit wichtiger Reformen. Lobbyarbeit wird jedoch auch zur Durchsetzung von Partikularinteressen eingesetzt. Die dabei herrschende Intransparenz des externen Einflusses ist häufig Gegenstand von Kritik. Diese Arbeit geht der Frage nach, ob sich die Lobbyaktivität bei Themen der Wirtschaftskommission des Nationalrats in den letzten 15 Jahren verändert hat. Hierzu werden die einflussreichsten Interessengruppen identifiziert. Wie wirksam diese den politischen Prozess beeinflussen, wird anhand des Bundesbeschlusses über die landwirtschaftlichen Zahlungsrahmen illustriert. Zusätzlich erfolgt eine Evaluation darüber, wie vollständig Wirtschaftspolitikerinnen und -politiker ihre externen Mandate deklarieren. Abgestützt auf die Erkenntnisse nimmt die Arbeit eine Lagebeurteilung der heute geltenden gesetzlichen Bedingungen des Lobbyings vor

Serologic Evidence of Human and Swine Influenza in Mayan Persons

Antibodies against influenza viruses were detected in 115 serum samples from indigenous Mayan persons from Kochol, Yucatán. Seropositivity rates were 26.9% to A/Bayern/7/95, 40.8% to A/Sydney/5/97, 1.7% to A/Swine/Wisconsin/238/97, and 79.1% to A/Swine/Minnesota/593/99. This report is the first in Mexico of the prevalence of antibodies to swine influenza virus in humans

Late Quaternary palaeoenvironment of northern Guatemala: evidence from deep drill cores and seismic stratigraphy of Lake Petén Itzá

Long sediment cores were collected in spring 2006 from Lake Petén Itzá, northern Guatemala, in water depths ranging from 30 to 150 m, as part of an International Continental Scientific Drilling Program project. The sediment records from deep water consist mainly of alternating clay, gypsum and carbonate units and, in at least two drill sites, extend back >200 kyr. Most of the lithostratigraphic units are traceable throughout the basin along seismic reflections that serve as seismic stratigraphic boundaries and suggest that the lithostratigraphy can be used to infer regional palaeoenvironmental changes. A revised seismic stratigraphy was established on the basis of integrated lithological and seismic reflection data from the basin. From ca 200 to ca 85 ka, sediments are dominated by carbonate-clay silt, often interbedded with sandy turbidites, indicating a sediment regime dominated by detrital sedimentation in a relatively humid climate. At ca 85 ka, an exposure horizon consisting of gravels, coarse sand and terrestrial gastropods marks a lake lowstand or partial basin desiccation, indicating dry climate conditions. From ca 85 to ca 48 ka, transgressive carbonate-clay sediments, overlain by deep-water clays, suggest a lake level rise and subsequent stabilization at high stage. From ca 48 ka to present, the lithology is characterized by alternating clay and gypsum units. Gypsum deposition correlates with Heinrich Events (i.e. dry climate), whereas clay units coincide with more humid interstadials

Potential and Actual Terrestrial Rabies Exposures in People and Domestic Animals, Upstate South Carolina, 1994–2004: A Surveillance Study

<p>Abstract</p> <p>Background</p> <p>Although there has been a reduction of rabies in pets and domestic animals during recent decades in the United States, rabies remains enzootic among bats and several species of terrestrial wildlife. Spillover transmission of wildlife rabies to domestic animals therefore remains a public health threat</p> <p>Methods</p> <p>Retrospective analysis of surveillance data of reported animal incidents (bites, scratches, mucous membrane contacts) from South Carolina, 1995 to 2003, was performed to assess risk factors of potential rabies exposures among human and animal victims.</p> <p>Results</p> <p>Dogs and cats contributed the majority (66.7% and 26.4%, respectively) of all reported incidents, with stray dogs and cats contributing 9.0% and 15.1 respectively. Current rabies vaccination status of dogs and cats (40.2% and 13.8%, respectively) were below World Health Organization recommended levels. Owned cats were half as likely to be vaccinated for rabies as dogs (OR 0.53, 95% CI 0.48, 0.58). Animal victims were primarily exposed to wildlife (83.0%), of which 27.5% were rabid. Almost 90% of confirmed rabies exposures were due to wildlife. Skunks had the highest prevalence of rabies among species of exposure animals (63.2%). Among rabid domestic animals, stray cats were the most commonly reported (47.4%).</p> <p>Conclusion</p> <p>While the majority of reported potential rabies exposures are associated with dog and cat incidents, most rabies exposures derive from rabid wildlife. Stray cats were most frequently rabid among domestic animals. Our results underscore the need for improvement of wildlife rabies control and the reduction of interactions of domestic animals, including cats, with wildlife.</p