Telotristat ethyl in carcinoid syndrome: safety and efficacy in the TELECAST phase 3 trial

Telotristat ethyl, a tryptophan hydroxylase inhibitor, was efficacious and well tolerated in the phase 3 TELESTAR study in patients with carcinoid syndrome (CS) experiencing ≥4 bowel movements per day (BMs/day) while on somatostatin analogs (SSAs). TELECAST, a phase 3 companion study, assessed the safety and efficacy of telotristat ethyl in patients with CS (diarrhea, flushing, abdominal pain, nausea or elevated urinary 5-hydroxyindoleacetic acid (u5-HIAA)) with <4 BMs/day on SSAs (or ≥1 symptom or ≥4 BMs/day if not on SSAs) during a 12-week double-blind treatment period followed by a 36-week open-label extension (OLE). The primary safety and efficacy endpoints were incidence of treatment-emergent adverse events (TEAEs) and percent change from baseline in 24-h u5-HIAA at week 12. Patients (N = 76) were randomly assigned (1:1:1) to receive placebo or telotristat ethyl 250 mg or 500 mg 3 times per day (tid); 67 continued receiving telotristat ethyl 500 mg tid during the OLE. Through week 12, TEAEs were generally mild to moderate in severity; 5 (placebo), 1 (telotristat ethyl 250 mg) and 3 (telotristat ethyl 500 mg) patients experienced serious events, and the rate of TEAEs in the OLE was comparable. At week 12, significant reductions in u5-HIAA from baseline were observed, with Hodges–Lehmann estimators of median treatment differences from placebo of −54.0% (95% confidence limits, −85.0%, −25.1%, P < 0.001) and −89.7% (95% confidence limits, −113.1%, −63.9%, P < 0.001) for telotristat ethyl 250 mg and 500 mg. These results support the safety and efficacy of telotristat ethyl when added to SSAs in patients with CS diarrhea (ClinicalTrials.gov identifier: Nbib2063659)

pyam: Analysis and visualisation of integrated assessment and macro-energy scenarios [version 2; peer review: 3 approved]

The open-source Python package pyam provides a suite of features and methods for the analysis, validation and visualization of reference data and scenario results generated by integrated assessment models, macro-energy tools and other frameworks in the domain of energy transition, climate change mitigation and sustainable development. It bridges the gap between scenario processing and visualisation solutions that are "hard-wired" to specific modelling frameworks and generic data analysis or plotting packages. The package aims to facilitate reproducibility and reliability of scenario processing, validation and analysis by providing well-tested and documented methods for working with timeseries data in the context of climate policy and energy systems. It supports various data formats, including sub-annual resolution using continuous time representation and "representative timeslices". The pyam package can be useful for modelers generating scenario results using their own tools as well as researchers and analysts working with existing scenario ensembles such as those supporting the IPCC reports or produced in research projects. It is structured in a way that it can be applied irrespective of a user's domain expertise or level of Python knowledge, supporting experts as well as novice users. The code base is implemented following best practices of collaborative scientific-software development. This manuscript describes the design principles of the package and the types of data which can be handled. The usefulness of pyam is illustrated by highlighting several recent applications

From the development of an open-source energy modelling tool to its application and the creation of communities of practice: The example of OSeMOSYS

In the last decades, energy modelling has supported energy planning by offering insights into the dynamics between energy access, resource use, and sustainable development. Especially in recent years, there has been an attempt to strengthen the science-policy interface and increase the involvement of society in energy planning processes. This has, both in the EU and worldwide, led to the development of open-source and transparent energy modelling practices. This paper describes the role of an open-source energy modelling tool in the energy planning process and highlights its importance for society. Specifically, it describes the existence and characteristics of the relationship between developing an open-source, freely available tool and its application, dissemination and use for policy making. Using the example of the Open Source energy Modelling System (OSeMOSYS), this work focuses on practices that were established within the community and that made the framework's development and application both relevant and scientifically grounded