(Self-) Enforcement of Joint Implementation and Clean Development Mechanism Contracts

International climate protection investments (Joint Implementation and Clean Development Mechanism projects) are burdened with problems of contract enforcement, which prevent the realisation of efficiency gains associated with these investments. The paper analyses this problem from the perspective of non-cooperative game theory and proposes two different solutions to the co-operation problem. The first analyses the potential role of national environmental authorities in facilitating credible commitment of the project host operating under its jurisdiction. It is argued that the threat of punishing the project host if he breaches the contract may serve this purpose. The effective level of punishment is derived. The second option involves strategic delegation of contract implementation to a third party operating under the same jurisdiction as the project host. Again, the paper explores the conditions that ensure incentive-compatibility. Both options are based on the idea that the project sponsor may commit himself credibly by becoming a Stackelberg leader.Joint Implementation, Clean Development Mechanism, climate protection, international environmental agreements, international investments, contract enforcement, co-operation, incentive compatibility

Harpacticoid copepods in a DEB framework : investigating pharmaceutical effects on Nitocra spinipes

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Strukturdaten des Naturkostfachhandels: Erhebung des Status quo und Aufbau eines Instrumentariums zur kontinuierlichen Strukturbeschreibung des Bio-Marktsegmentes Naturkostfachhandel

Der spezialisierte Naturkosthandel stellt in Deutschland traditionell einen wichtigen Absatzkanal für Öko-Lebensmittel dar. Zu Beginn des zweijährigen Projektes im Dezember 2009 lagen zu den Strukturen der Branche keine vollständigen und abgesicherten Daten vor. Dies galt insbesondere für den Naturkosteinzelhandel, aber auch den Naturkostgroßhandel. Es bestand eine relativ hohe Marktintransparenz. Vor diesem Hintergrund zielte das Vorhaben zunächst auf die Erhebung der Grundgesamtheit des Naturkosteinzelhandels ab. Zum Oktober 2010 wurden 2.346 Naturfachgeschäfte ermittelt. Aus der Grundgesamtheit wurde eine repräsentative Stichprobe von 319 Geschäften für die Durchführung von Face-to-Face-Interviews gezogen. Im Ergebnis lagen auswertbare Daten von 254 Geschäften vor, die detaillierte Auskünfte über u. a. Verkaufsflächen, Umsätze, Sortimentsstrukturen und Bezugsquellen der Einzelhändler ermöglichen. Zur Analyse der Großhandelsstrukturen wurden rund 131 Großhändler und Hersteller, die den Naturkosteinzelhandel direkt beliefern, telefonisch kontaktiert und nach bestimmten Kriterien befragt. Mit einer weitergehenden schriftlichen Befragung konnten auswertbare Ergebnisse von 28 Unternehmen erzielt werden, die erstmals vertiefte Einblicke in Umsätze sowie die Umsatzanteile verschiedener Kundengruppen und Sortimente geben. Auf der Grundlage der erhobenen Daten wurde ein Verfahren zur Hochrechnung des Marktvolumens der Naturkostbranche erarbeitet. Dazu wurden sechs verschiedene Varianten getestet und diskutiert. Die letztlich ausgewählte Variante kommt zu dem Ergebnis, dass das Marktvolumen des Naturkostfachhandels im Jahr 2009 1,77 Milliarden Euro betrug. Abschließend wurden mögliche Varianten für eine Datenfortschreibung (Strukturdaten und Hochrechnung des Marktvolumens) diskutiert. Dieses erfolgte sowohl auf der Basis der im Projekt erhobenen Daten als auch auf der Basis von bestehenden Datenquellen, die Teile der Naturkostbranche im Rahmen von Stichproben abbilden

Проблемы повышения эффективности инвестиций в образование

Определяются масштабы и эффективность инвестиций в образование, научные исследования и разработки. Обосновывается необходимость изменения социального статуса системы образования и увеличения масштабов финансирования как необходимого условия повышения качества подготовки специалистов

Imaging-based frequency mapping for cochlear implants – Evaluated using a daily randomized controlled trial

BackgroundDue to variation in electrode design, insertion depth and cochlear morphology, patients with a cochlear implant (CI) often have to adapt to a substantial mismatch between the characteristic response frequencies of cochlear neurons and the stimulus frequencies assigned to electrode contacts. We introduce an imaging-based fitting intervention, which aimed to reduce frequency-to-place mismatch by aligning frequency mapping with the tonotopic position of electrodes. Results were evaluated in a novel trial set-up where subjects crossed over between intervention and control using a daily within-patient randomized approach, immediately from the start of CI rehabilitation.MethodsFourteen adult participants were included in this single-blinded, daily randomized clinical trial. Based on a fusion of pre-operative imaging and a post-operative cone beam CT scan (CBCT), mapping of electrical input was aligned to natural place-pitch arrangement in the individual cochlea. That is, adjustments to the CI’s frequency allocation table were made so electrical stimulation of frequencies matched as closely as possible with corresponding acoustic locations in the cochlea. For a period of three months, starting at first fit, a scheme was implemented whereby the blinded subject crossed over between the experimental and standard fitting program using a daily randomized wearing schedule, and thus effectively acted as their own control. Speech outcomes (such as speech intelligibility in quiet and noise, sound quality and listening effort) were measured with both settings throughout the study period.ResultsOn a group level, standard fitting obtained subject preference and showed superior results in all outcome measures. In contrast, two out of fourteen subjects preferred the imaging-based fitting and correspondingly had better speech understanding with this setting compared to standard fitting.ConclusionOn average, cochlear implant fitting based on individual tonotopy did not elicit higher speech intelligibility but variability in individual results strengthen the potential for individualized frequency fitting. The novel trial design proved to be a suitable method for evaluation of experimental interventions in a prospective trial setup with cochlear implants

Single cell immune profiling by mass cytometry of newly diagnosed chronic phase chronic myeloid leukemia treated with nilotinib

Monitoring of single cell signal transduction in leukemic cellular subsets has been proposed to provide deeper understanding of disease biology and prognosis, but has so far not been tested in a clinical trial of targeted therapy. We developed a complete mass cytometry analysis pipeline for characterization of intracellular signal transduction patterns in the major leukocyte subsets of chronic phase chronic myeloid leukemia. Changes in phosphorylated Bcr-Abl1 and the signaling pathways involved were readily identifiable in peripheral blood single cells already within three hours of the patient receiving oral nilotinib. The signal transduction profiles of healthy donors were clearly distinct from those of the patients at diagnosis. Furthermore, using principal component analysis, we could show that phosphorylated transcription factors STAT3 (Y705) and CREB (S133) within seven days reflected BCR-ABL1(IS) at three and six months. Analyses of peripheral blood cells longitudinally collected from patients in the ENEST1st clinical trial showed that single cell mass cytometry appears to be highly suitable for future investigations addressing tyrosine kinase inhibitor dosing and effect. (clinicaltrials. gov identifier: 01061177)Peer reviewe

Severe neurocognitive and growth disorders due to variation in THOC2, an essential component of nuclear mRNA export machinery

Highly conserved TREX-mediated mRNA export is emerging as a key pathway in neuronal development and differentiation. TREX subunit variants cause neurodevelopmental disorders (NDDs) by interfering with mRNA export from the cell nucleus to the cytoplasm. Previously we implicated four missense variants in the X-linked THOC2 gene in intellectual disability (ID). We now report an additional six affected individuals from five unrelated families with two de novo and threematernally inherited pathogenic or likely pathogenic variants in THOC2 extending the genotypic and phenotypic spectrum. These comprise three rare missense THOC2 variants that affect evolutionarily conserved amino acid residues and reduce protein stability and two with canonical splice-site THOC2 variants that result in C-terminally truncated THOC2 proteins.We present detailed clinical assessment and functional studies on a de novo variant in a female with an epileptic encephalopathy and discuss an additional four families with rare variants in THOC2 with supportive evidence for pathogenicity. Severe neurocognitive features, including movement and seizure disorders, were observed in this cohort. Taken together our data show that even subtle alterations to the canonical molecular pathways such asmRNAexport, otherwise essential for cellular life, can be compatible with life, but lead to NDDs in human