Final results from the PERUSE study of first-line pertuzumab plus trastuzumab plus a taxane for HER2-positive locally recurrent or metastatic breast cancer, with a multivariable approach to guide prognostication

Background: The phase III CLinical Evaluation Of Pertuzumab And TRAstuzumab (CLEOPATRA) trial established the combination of pertuzumab, trastuzumab and docetaxel as standard first-line therapy for human epidermal growth factor receptor 2 (HER2)-positive locally recurrent/metastatic breast cancer (LR/mBC). The multicentre single-arm PERtUzumab global SafEty (PERUSE) study assessed the safety and efficacy of pertuzumab and trastuzumab combined with investigator-selected taxane in this setting. Patients and methods: Eligible patients with inoperable HER2-positive LR/mBC and no prior systemic therapy for LR/mBC (except endocrine therapy) received docetaxel, paclitaxel or nab-paclitaxel with trastuzumab and pertuzumab until disease progression or unacceptable toxicity. The primary endpoint was safety. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). Prespecified subgroup analyses included subgroups according to taxane, hormone receptor (HR) status and prior trastuzumab. Exploratory univariable analyses identified potential prognostic factors; those that remained significant in multivariable analysis were used to analyse PFS and OS in subgroups with all, some or none of these factors. Results: Of 1436 treated patients, 588 (41%) initially received paclitaxel and 918 (64%) had HR-positive disease. The most common grade 653 adverse events were neutropenia (10%, mainly with docetaxel) and diarrhoea (8%). At the final analysis (median follow-up: 5.7 years), median PFS was 20.7 [95% confidence interval (CI) 18.9-23.1] months overall and was similar irrespective of HR status or taxane. Median OS was 65.3 (95% CI 60.9-70.9) months overall. OS was similar regardless of taxane backbone but was more favourable in patients with HR-positive than HR-negative LR/mBC. In exploratory analyses, trastuzumab-pretreated patients with visceral disease had the shortest median PFS (13.1 months) and OS (46.3 months). Conclusions: Mature results from PERUSE show a safety and efficacy profile consistent with results from CLEOPATRA and median OS exceeding 5 years. Results suggest that paclitaxel is a valid alternative to docetaxel as backbone chemotherapy. Exploratory analyses suggest risk factors that could guide future trial design

Global wealth disparities drive adherence to COVID-safe pathways in head and neck cancer surgery

Peer reviewe

Toward a Coordinated Global Observing System for Seagrasses and Marine Macroalgae

In coastal waters around the world, the dominant primary producers are benthic macrophytes, including seagrasses and macroalgae, that provide habitat structure and food for diverse and abundant biological communities and drive ecosystem processes. Seagrass meadows and macroalgal forests play key roles for coastal societies, contributing to fishery yields, storm protection, biogeochemical cycling and storage, and important cultural values. These socio-economically valuable services are threatened worldwide by human activities, with substantial areas of seagrass and macroalgal forests lost over the last half-century. Tracking the status and trends in marine macrophyte cover and quality is an emerging priority for ocean and coastal management, but doing so has been challenged by limited coordination across the numerous efforts to monitor macrophytes, which vary widely in goals, methodologies, scales, capacity, governance approaches, and data availability. Here, we present a consensus assessment and recommendations on the current state of and opportunities for advancing global marine macrophyte observations, integrating contributions from a community of researchers with broad geographic and disciplinary expertise. With the increasing scale of human impacts, the time is ripe to harmonize marine macrophyte observations by building on existing networks and identifying a core set of common metrics and approaches in sampling design, field measurements, governance, capacity building, and data management. We recommend a tiered observation system, with improvement of remote sensing and remote underwater imaging to expand capacity to capture broad-scale extent at intervals of several years, coordinated with stratified in situ sampling annually to characterize the key variables of cover and taxonomic or functional group composition, and to provide ground-truth. A robust networked system of macrophyte observations will be facilitated by establishing best practices, including standard protocols, documentation, and sharing of resources at all stages of workflow, and secure archiving of open-access data. Because such a network is necessarily distributed, sustaining it depends on close engagement of local stakeholders and focusing on building and long-term maintenance of local capacity, particularly in the developing world. Realizing these recommendations will produce more effective, efficient, and responsive observing, a more accurate global picture of change in vegetated coastal systems, and stronger international capacity for sustaining observations

Sizing BESS for a peak shaving and valley filling control strategy for residential consumers based on their load-duration curves

Driven by the renewable energy transition and the increasing penetration of distributed generation on the distribution grid, many countries are rethinking their electricity tariff structures. The focus is shifting towards capacity-based grid tariffs, with users being charged more for their peak demands in order to make the tariff structure more cost-reflective. However, a group of residential consumers will be subjected to changing grid tariffs without established technologies, e.g. PV. To lower their invoice, they can only change their consumption behaviour via e.g. load shifting, as not all rooftops are suitable for PV installations. Consequently, this work investigates the sizing of battery storage systems for peak shaving purposes at the level of the individual household in the absence of local generation. We propose using the analytic form of the load-duration curve to determine the peak shaving threshold. The results show that on average under the proposed sizing methodology, the battery remains idle for more than 95% of the time while realising a mean monthly peak reduction of 50%. Therefore, the battery could and should provide additional services through aggregators at the low-voltage level, which would provide necessary complementary revenue streams that make such a system economically viable

Onderzoek naar de impact van het capaciteitstarief

Deze studie behelst het onderzoek naar de impact van de nieuwe tariefstructuur voor residentiële eindverbruikers. Vanaf midden 2022 verandert immers de wijze waarop de nettarieven, een onderdeel van de elektriciteitsfactuur, samengesteld worden. Waar de nettarieven momenteel voornamelijk verbruiksafhankelijk zijn, en dus gebaseerd op de kWh-afname, introduceert de Vlaamse Regulator van de Elektriciteits- en Gasmarkt (VREG) in 2022 een nieuwe tariefdrager, het zogenoemde capaciteitstarief. Dit capaciteitstarief wordt voor verbruikers met een digitale meter bepaald op basis van hun uitgemiddelde maandpiek—vermogensterm genoemd - terwijl huishoudens met een klassieke meter een vaste bijdrage voor die vermogensterm zullen moeten betalen. Op basis van historische verbruiksgegevens wordt de impact van de wijzigende nettarieven op de elektriciteitsfactuur in kaart gebracht voor diverse types huishoudens (kleine of grote verbruikers, met en zonder elektrische (accumulatie) verwarming, aanwezigheid zonnepanelen, beschermde afnemers, etc.). Deze impact wordt bekeken zowel voor de klassieke als de digitale meter en naast elkaar gezet. Voor huishoudens met zonnepanelen worden zowel prosumenten met een terugdraaiende teller beschouwd als huishoudens met een digitale meter die op hun werkelijke afname gefactureerd worden. Finaal wordt de rol van het capaciteitstarief in de energietransitie onderzocht en indien het capaciteitstarief de gewenste elektrificatie bevordert. Meer specifiek wordt de elektrificatie van mobiliteits- en warmtevraag in de vorm van elektrische voertuigen en warmtepompen onderzocht, gelet op hun rol binnen het Vlaams Energieen Klimaatplan

Laagspanningsinstallaties : technologie en ontwerp

“Laagspanningsinstallaties: technologie en ontwerp” bevat naast de wetenschappelijke insteek tal van praktische richtlijnen voor de optimale, energiebewuste, veilige en vooral de bedrijfszekere uitbating van een industriële installatie. Deze vierde druk is aangepast aan de meest recente versie van het AREI en uitgebreid met de Synergrid richtlijnen over het integreren van hernieuwbare energie en opslag