PUTTING VALUE CO-CREATION INTO PRACTICE: A CASE FOR ADVISORY SUPPORT

The concept of value co-creation and its notion of the customer as co-creator of value have gained much academic interest, notably in marketing and operations research. While several competing perspectives have been conceptually discussed in literature, research on the practical implications of value co-creation is scarce. Using the example of sales-oriented advisory, we show gaps between existing co-creation concepts and current practice in five problem areas. We develop four general solution perspectives on the advisor-client encounter as guidelines to overcome these gaps and discuss design requirements of their technological instantiations in advisory support systems. We present exemplary implementations of such systems in two domains: travel counseling and financial advisory. Revealing the practical implications of value co-creation on advisory encounters, these examples also demonstrate that the solution perspectives have to be implemented quite differently for individual domains

Untersuchungen zu GABAA-Modulatoren aus Juncus effusus L.

Das getrocknete Stängelmark aus Juncus effusus wird in der Traditionellen Chinesischen Medizin als Schlafmittel verwendet. Der Wirkmechanismus ist bisher allerdings unbekannt. In dieser Arbeit wurde der Ethylacetat-Extrakt dieser Droge bioaktivitätsgeleitet aufgetrennt. Es wurde ein DC-System erarbeitet, das der Kontrolle der Fraktionierung diente. Anschließend wurde der Extrakt zuerst an Kieselgel und die daraus erhaltenen aktiven Fraktionen später an Sephadex LH-20 aufgetrennt. Einige der getesteten Fraktionen erzielten eine eindeutig positiv-modulatorische Wirkung an GABAA-Rezeptoren. Somit konnte gezeigt werden, dass das getrocknete Stängelmark aus Juncus effusus Substanzen enthält, die an GABAA-Rezeptoren wirken und daher möglicherweise für den ethnopharmakologischen Gebrauch dieser Droge als Sedativum verantwortlich sind

Wipe sampling procedure coupled to LC-MS/MS analysis for the simultaneous determination of 10 cytotoxic drugs on different surfaces

A simple wipe sampling procedure was developed for the surface contamination determination of ten cytotoxic drugs: cytarabine, gemcitabine, methotrexate, etoposide phosphate, cyclophosphamide, ifosfamide, irinotecan, doxorubicin, epirubicin and vincristine. Wiping was performed using Whatman filter paper on different surfaces such as stainless steel, polypropylene, polystyrol, glass, latex gloves, computer mouse and coated paperboard. Wiping and desorption procedures were investigated: The same solution containing 20% acetonitrile and 0.1% formic acid in water gave the best results. After ultrasonic desorption and then centrifugation, samples were analysed by a validated liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) in selected reaction monitoring mode. The whole analytical strategy from wipe sampling to LC-MS/MS analysis was evaluated to determine quantitative performance. The lowest limit of quantification of 10ng per wiping sample (i.e. 0.1ngcm−2) was determined for the ten investigated cytotoxic drugs. Relative standard deviation for intermediate precision was always inferior to 20%. As recovery was dependent on the tested surface for each drug, a correction factor was determined and applied for real samples. The method was then successfully applied at the cytotoxic production unit of the Geneva University Hospitals pharmacy. Figure Wipe sampling procedure for the determination of cytotoxic drug

Evaluation of Decontamination Efficacy of Cleaning Solutions on Stainless Steel and Glass Surfaces Contaminated by 10 Antineoplastic Agents

Objectives: The handling of antineoplastic agents results in chronic surface contamination that must be minimized and eliminated. This study was designed to assess the potential of several chemical solutions to decontaminate two types of work surfaces that were intentionally contaminated with antineoplastic drugs. Methods: A range of solutions with variable physicochemical properties such as their hydrophilic/hydrophobic balance, oxidizing power, desorption, and solubilization were tested: ultrapure water, isopropyl alcohol, acetone, sodium hypochlorite, and surfactants such as dishwashing liquid (DWL), sodium dodecyl sulfate (SDS), Tween 40, and Span 80. These solutions were tested on 10 antineoplastic drugs: cytarabine, gemcitabine, methotrexate, etoposide phosphate, irinotecan, cyclophosphamide, ifosfamide, doxorubicin, epirubicin, and vincristine. To simulate contaminated surfaces, these molecules (200ng) were deliberately spread onto two types of work surfaces: stainless steel and glass. Recovered by wiping with a specific aqueous solvent (acetonitrile/HCOOH; 20/0.1%) and an absorbent wipe (Whatman 903®), the residual contamination was quantified using high-performance liquid chromatography (HPLC) coupled to mass spectrometry. To compare all tested cleaning solutions, a performance value of effectiveness was determined from contamination residues of the 10 drugs. Results: Sodium hypochlorite showed the highest overall effectiveness with 98% contamination removed. Ultrapure water, isopropyl alcohol/water, and acetone were less effective with effectiveness values of 76.8, 80.7, and 40.4%, respectively. Ultrapure water was effective on most hydrophilic molecules (97.1% for cytarabine), while on the other hand, isopropyl alcohol/water (70/30, vol/vol) was effective on the least hydrophilic ones (85.2% for doxorubicin and 87.8% for epirubicin). Acetone had little effect, whatever the type of molecule. Among products containing surfactants, DWL was found effective (91.5%), but its formulation was unknown. Formulations with single surfactant non-ionics (tween 40 and span 80) or anionic (SDS) were also tested. Finally, solutions containing 10-2 M anionic surfactants and 20% isopropyl alcohol had the highest global effectiveness at around 90%. More precisely, their efficacy was the highest (94.8%) for the most hydrophilic compounds such as cytarabine and around 80.0% for anthracyclines. Finally, the addition of isopropyl alcohol to surfactant solutions enhanced their decontamination efficiency on the least hydrophilic molecules. Measured values from the stainless steel surface were similar to those from the glass one. Conclusion: This study demonstrates that all decontamination agents reduce antineoplastic contamination on work surfaces, but none removes it totally. Although very effective, sodium hypochlorite cannot be used routinely on stainless steel surfaces. Solutions containing anionic surfactant such as SDS, with a high efficiency/safety ratio, proved most promising in terms of surface decontaminatio

Simultaneous quantification of ten cytotoxic drugs by a validated LC-ESI-MS/MS method

A liquid chromatography separation with electrospray ionisation and tandem mass spectrometry detection method was developed for the simultaneous quantification of ten commonly handled cytotoxic drugs in a hospital pharmacy. These cytotoxic drugs are cytarabine, gemcitabine, methotrexate, etoposide phosphate, cyclophosphamide, ifosfamide, irinotecan, doxorubicin, epirubicin and vincristine. The chromatographic separation was carried out by RPLC in less than 21min, applying a gradient elution of water and acetonitrile in the presence of 0.1% formic acid. MS/MS was performed on a triple quadrupole in selected reaction monitoring mode. The analytical method was validated to determine the limit of quantification (LOQ) and quantitative performance: lowest LOQs were between 0.25 and 2ngmL−1 for the ten investigated cytotoxic drugs; trueness values (i.e. recovery) were between 85% and 110%, and relative standard deviations for both repeatability and intermediate precision were always inferior to 15%. The multi-compound method was successfully applied for the quality control of pharmaceutical formulations and for analyses of spiked samples on potentially contaminated surfaces. Figure Preparation of cytotoxic formulations at the Pharmacy of Geneva University Hospital

Vida y medios de subsistencia más seguros en las montañas: Cómo lograr que el Marco de Sendai para la Reducción del Riesgo de Desastres trabaje para el desarrollo sostenible de las regiones de montaña

Mountain systems are very diverse and so is the pattern of natural hazards. Worldwide disaster databases show that associated human and economic losses are significant but vary greatly between and within mountain regions. Continued changes in climate, land use and socio-economic conditions are likely to lead to vastly altered mountain landscapes in the future, with associated implications for hazards and impacts on sustainable mountain development

Grey wolf genomic history reveals a dual ancestry of dogs

The grey wolf (Canis lupus) was the first species to give rise to a domestic population, and they remained widespread throughout the last Ice Age when many other large mammal species went extinct. Little is known, however, about the history and possible extinction of past wolf populations or when and where the wolf progenitors of the present-day dog lineage (Canisfamiliaris) lived(1-8). Here we analysed 72 ancient wolf genomes spanning the last 100,000 years from Europe, Siberia and North America. We found that wolf populations were highly connected throughout the Late Pleistocene, with levels of differentiation an order of magnitude lower than they are today. This population connectivity allowed us to detect natural selection across the time series, including rapid fixation of mutations in the gene IFT8840,000-30,000 years ago. We show that dogs are overall more closely related to ancient wolves from eastern Eurasia than to those from western Eurasia, suggesting a domestication process in the east. However, we also found that dogs in the Near East and Africa derive up to half of their ancestry from a distinct population related to modern southwest Eurasian wolves, reflecting either an independent domestication process or admixture from local wolves. None of the analysed ancient wolf genomes is a direct match for either of these dog ancestries, meaning that the exact progenitor populations remain to be located.Peer reviewe

Screening of biological samples by SWATH acquisition and forensic toxicological applications

Fast and accurate screening of biological samples is an important step in forensic toxicology for further decisions regarding possible quantification of the detected compounds in body fluids or tissues, investigations and prosecution. Based on Quadrupole Time-of-Flight (QqTOF) mass spectrometers – which are capable of acquiring complete MS and MS/MS spectra at a rate of 20 Hz or more and high mass accuracy – a new screening methodology was developed, validated and implemented in the forensic toxicological workflow. Urine samples were diluted with a mixture of water / acetonitrile / formic acid / ammonium formate (97.5 / 2.5 / 0.1% / 2.5 mM) and three internal standards were added (EME-D3, Tramadol-D3C13, THC-D3). Blood or plasma samples were prepared by protein precipitation. The samples were injected onto a core shell column (Phenomenex Kinetex C8, 50 x 2.1 mm, 2.6 μm) and analyzed on a QqTOF instrument (5600 TripleTOF, AB Sciex, Concord, Canada) with typical run times of 15 minutes from injection to injection. The methodology is based on sequential window acquisition of all theoretical fragment ions spectra (SWATH) and high resolution/high accuracy reference spectra which are used for data processing. Several forensic cases and applications are presented and the impact of this mass spectrometry based technique in the field of forensic toxicology is discussed

Analyse de médicaments produits en milieu hospitalier : applications aux composés non-UV absorbants et cytotoxiques

L'analyse de médicaments produits en milieu hospitalier revêt un grand intérêt du point de vue qualité et sécurité des traitements médicamenteux non seulement pour le patient mais aussi pour les personnes manipulant ces médicaments. Au cours de cette thèse, différentes méthodes d'analyse ayant pour objectif la détermination de composés non-UV absorbants et de substances cytotoxiques contenus dans des formulations produites en milieu hospitalier ont été développées pour le contrôle qualité et le contrôle de'environnement. Plusieurs techniques ont été étudiées: L'électrophorèse capillaire couplée à des systèmes de détection de type UV/Vis ou conductimétrique sans contact avec le capillaire a permis de déterminer plusieurs substances actives contenues dans des formulations produites à l'hôpital. La chromatographie liquide couplée à la spectrométrie de masse a été employée pour déterminer la contamination par des cytotoxiques sur différentes surfaces de locaux de production de pharmacies hospitalières

Diverse natural hazards – high human and economic losses

Mountain systems are very diverse and so is the pattern of natural hazards. Worldwide disaster databases show that associated human and economic losses are significant but vary greatly between and within mountain regions. Continued changes in climate, land use and socio-economic conditions are likely to lead to vastly altered mountain landscapes in the future, with associated implications for hazards and impacts on sustainable mountain development