Long-term renal safety profile of ibandronate 6 mg infused over 15 minutes

In an earlier study, intravenous (i.v.) ibandronate 6 mg administered every 3-4 weeks had a similarly good renal safety profile whether infused over 15 or 60 min in women with breast cancer and bone metastases. This current study focuses on the renal safety of the extended use of ibandronate

Embracing open innovation to acquire external ideas and technologies and to transfer internal ideas and technologies outside

The objective of this dissertation is to increase understanding of how organizations can embrace open innovation in order to acquire external ideas and technologies from outside the organization, and to transfer internal ideas and technologies to outside the organization. The objective encompasses six sub-objectives, each addressed in one or more substudies. Altogether, the dissertation consists of nine substudies and a compendium summarizing the substudies. An extensive literature review was conducted on open innovation and crowdsourcing literature (substudies 1–4). In the subsequent empirical substudies, both qualitative research methods (substudies 5–7) and quantitative research methods (substudies 8–9) were applied. The four literature review substudies provided insights on the body of knowledge on open innovation and crowdsourcing. These substudies unveiled most of the influential articles, authors, and journals of open innovation and crowdsourcing disciplines. Moreover, they identified research gaps in the current literature. The empirical substudies offer several insightful findings. Substudy 5 shows how non-core ideas and technologies of a large firm can become valuable, especially for small firms. Intermediary platforms can find solutions to many pressing problems of large organizations by engaging renowned scientists from all over world (substudy 6). Intermediary platforms can also bring breakthrough innovations with novel mechanisms (substudy 7). Large firms are not only able to garner ideas by engaging their customers through crowdsourcing but they can also build long-lasting relations with their customers (substudies 8 and 9). Embracing open innovation brings challenges for firms too. Firms need to change their organizational structures in order to be able to fully benefit from open innovation. When crowdsourcing is successful, it produces a very large number of new ideas. This has the consequence that firms need to allocate a significant amount of resources in order to identify the most promising ideas. In an idea contest, customarily, only one or a few best ideas are rewarded (substudy 7). Sometimes, no reward is provided for the selected idea (substudies 8 and 9). Most of the ideas that are received are not implemented in practice

Analyse von Anästhesiezwischenfällen von 1995 bis 2004 an der Pferdeklinik der Vetsuisse-Fakultät der Universität Zürich

Grund der Studie: Es soll evaluiert werden, wie hoch die Mortalität bei Pferdeanästhesien an der Universitätsklinik Zürich in den letzten 10 Jahren war. Risikofaktoren sollen ermittelt werden. Hypothese: An der Universitätsklinik Zürich ist die Rate der Anästhesiezwischenfälle im Vergleich zu anderen Kliniken geringer. Methoden: Es wurden alle Anästhesieprotokolle der letzten 10 Jahre untersucht. Insgesamt wurden 4866 Fälle evaluiert. Folgende Parameter aller Anästhesien wurden notiert: Angaben zum Pferd, verwendete Medikamente, Operationsart- und Dauer. Bei Pferden, die innerhalb von 7 Tagen euthanasiert wurden oder starben, wurde evaluiert, ob der Tod des Tieres mit der Anästhesie zusammenhing oder nicht. Resultate: An der Universitätsklinik Zürich sind 0.51 % der Pferde wegen eines Anästhesieproblems gestorben oder euthanasiert worden. Bei den Routinepatienten lag die Zwischenfallsrate bei 0.11 %, bei den Notfallpatienten bei 1.7 %, nach Ausschluss der Notfallkoliker lag sie bei 0.24 % und für die Notfall-Koliker bei 2.0 %. Ein erhöhtes Anästhesierisiko bestand für Operationsdauern unter 60 oder über 240 Minuten, Koliker- oder Frakturpatienten, Notfalloperationen sowie für Pferde, die keine sedierenden Medikamente während der Aufwachphase erhalten hatten. Schlussfolgerung: Durch ein gutes peri- und intraoperatives Management ist das Anästhesierisiko ist für Pferde der Universität Zürich, im Vergleich zu anderen Universitäten, 3 bis 10 mal geringer. Objectives: To document the equine perioperative mortality rate at the equine clinic of the University Hospital of Zurich during the last 10 years and to highlight any factor associated with an increased risk of death up to 7 days after anaesthesia. Hypothesis: The rate of anaesthesia incidents in comparison to other clinics is reduced. Methods: Data were recorded from all equine undergoing general anaesthesia during the last 10 years. Calculations indicated that 4866 cases were required to detect the significance of important variables. The following parameters were recorded: Details of each horse, anaesthetic agents, type of surgery. Outcome at 7 days was recorded as alive, euthanased or dead. If they died it was analysed whether they died in relation to anaesthesia or not. Results: In 0.51 % of the analysed cases, the patients died or were euthanased because of anaesthesia problems. If emergency patients were excluded the death rate was 0.11 %. In emergency patients the death rate was 1.7 %. If all emergency abdominal surgeries were excluded the death rate was 0.24 %, for the emergency abdominal surgeries it was 2.0 %. An operation duration of less than 60 minutes or more than 240 minutes, colic operation or fracture repair, emergency operations as well as if there was no sedation during recovery was associated with increased risk of dying. Conclusion: Fatality rate in equine at the University of Zurich is reduced in comparison to other universities. Compared with other studies there was a 3 to 10 time lower anaesthesia risk

Scalable Synthesis of Enantiomerically Pure Bicyclo[2.2.2]octadiene Ligands

An operationally simple and scalable synthesis of enantiomerically pure bicyclo[2.2.2]­octadiene (bod*) ligands relying on an organocatalytic one-pot Michael addition–aldol reaction with cheap 2-cyclohexenone and phenylacetaldehyde is presented. The crystalline bicyclic product <b>4a</b> (6-hydroxy-5-phenylbicyclo[2.2.2]­octan-2-one) is transformed into phenylbicyclo[2.2.2]­oct-5-en-2-one <b>2</b>, a versatile starting material for the 2-step synthesis of both symmetrical, such as Hayashi’s Ph-bod* ligand, as well as novel unsymmetrical chiral dienes

Scalable Synthesis of Enantiomerically Pure Bicyclo[2.2.2]octadiene Ligands

An operationally simple and scalable synthesis of enantiomerically pure bicyclo[2.2.2]­octadiene (bod*) ligands relying on an organocatalytic one-pot Michael addition–aldol reaction with cheap 2-cyclohexenone and phenylacetaldehyde is presented. The crystalline bicyclic product <b>4a</b> (6-hydroxy-5-phenylbicyclo[2.2.2]­octan-2-one) is transformed into phenylbicyclo[2.2.2]­oct-5-en-2-one <b>2</b>, a versatile starting material for the 2-step synthesis of both symmetrical, such as Hayashi’s Ph-bod* ligand, as well as novel unsymmetrical chiral dienes

Design and Scale-Up of a Practical Enantioselective Route to 5-Phenylbicyclo[2.2.2]oct-5-en-2-one

A practical enantioselective route to chiral 5-phenylbicyclo[2.2.2]­oct-5-en-2-one <b>1</b> has been designed and developed. The target compound has been obtained as colorless crystals in 22% yield from 2-cyclohexenone, with an enantiomeric ratio higher than 99.5:0.5 and notably high chemical purity (> 99%). Three intermediates out of nine chemical steps are isolated. It is noteworthy that this process is devoid of any chromatography or distillation although all but one intermediate are oils. Key to success was the optimization of an intramolecular aldol reaction of an in situ prepared ketone aldehyde leading to the solid intermediate (1<i>R</i>,4<i>R</i>,4<i>S</i>,6<i>S</i>)-6-hydroxybicyclo­[2.2.2]­octan-2-one <b>9a</b> that is isolated in very high chemical and chiral purity. This is an example of an intramolecular crystallization-induced diastereomer transformation (CIDT). The dehydration of this secondary alcohol to <b>1</b> required an extensive screen of reaction conditions to secure an excellent purity, essential for crystallization of this low-melting compound. The final process is simple and concentrated as demonstrated by an expeditious synthesis of 1 kg of <b>1</b> in a 30-L reactor in 10 working days

Continuous Sunitinib treatment in patients with advanced hepatocellular carcinoma: a Swiss Group for Clinical Cancer Research (SAKK) and Swiss Association for the Study of the Liver (SASL) multicenter phase II trial (SAKK 77/06).

BACKGROUND: Sunitinib (SU) is a multitargeted tyrosine kinase inhibitor with antitumor and antiangiogenic activity. The objective of this trial was to demonstrate antitumor activity of continuous SU treatment in patients with hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Key eligibility criteria included unresectable or metastatic HCC, no prior systemic anticancer treatment, measurable disease, and Child-Pugh class A or mild Child-Pugh class B liver dysfunction. Patients received 37.5 mg SU daily until progression or unacceptable toxicity. The primary endpoint was progression-free survival at 12 weeks (PFS12). RESULTS: Forty-five patients were enrolled. The median age was 63 years; 89% had Child-Pugh class A disease and 47% had distant metastases. PFS12 was rated successful in 15 patients (33%; 95% confidence interval, 20%-47%). Over the whole trial period, one complete response and a 40% rate of stable disease as the best response were achieved. The median PFS duration, disease stabilization duration, time to progression, and overall survival time were 1.5, 2.9, 1.5, and 9.3 months, respectively. Grade 3 and 4 adverse events were infrequent. None of the 33 deaths were considered drug related. CONCLUSION: Continuous SU treatment with 37.5 mg daily is feasible and has moderate activity in patients with advanced HCC and mild to moderately impaired liver dysfunction. Under this trial design (&gt;13 PFS12 successes), the therapy is considered promising. This is the first trial describing the clinical effects of continuous dosing of SU in HCC patients on a schedule that is used in an ongoing, randomized, phase III trial in comparison with the current treatment standard, sorafenib (ClinicalTrials.gov identifier, NCT00699374)