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Environmental changes associated with rapid climate change in the Arctic, such as the increased rates of sedimentation from climatic or anthropogenic sources, can enhance the impact of abiotic stressors on coastal ecosystems. High sedimentation rates can be detrimental to nearshore kelp abundance and distribution, possibly due to increased mortality at the spore settlement stage. Spore settlement and viability of the Arctic kelp Laminaria solidungula were examined through a series of lab-based sedimentation experiments. Spores were exposed to increasing sediment loads in three experimental designs simulating different sedimentation scenarios: sediment deposition above settled spores, settlement of spores on sediment-covered substrate, and simultaneous suspension of spores and sediments during settlement. Spore settlement was recorded upon completion of each experiment, and gametophyte abundance was assessed following a growth period with sediments removed to examine short-term spore viability via a gametophyte-to-settled-spore ratio. In all three types of sediment exposure, the addition of sediments caused a 30%-40% reduction in spore settlement relative to a no-sediment control. Spore settlement decreased significantly between the low and high sediment treatments when spores were settled onto sediment-covered substrates. In all experiments, increasing amounts of sediment had no significant effect on spore viability, indicating that spores that had settled under different short-term sediment conditions were viable. Our results indicate that depending on spore-sediment interaction type, higher rates of sedimentation resulting from increased sediment loading could affect L. solidungula spore settlement success with potential impacts on the long-term persistence of a diverse and productive benthic habitat., (© 2024 Phycological Society of America.)

Background: In DESTINY-Breast02, patients with HER2-positive unresectable or metastatic breast cancer who received trastuzumab deruxtecan demonstrated superior progression-free and overall survival compared with those receiving treatment of physician's choice. We present the patient-reported outcomes (PROs) and hospitalisation data., Methods: In this randomised, open-label, phase 3 trial conducted at 227 clinical sites globally, enrolled patients had to be aged 18 years or older with HER2-positive unresectable or metastatic breast cancer that had progressed on trastuzumab emtansine and had an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomly assigned (2:1) using block randomisation (block size of 3) to receive trastuzumab deruxtecan (5·4 mg/kg intravenously once every 21 days) or treatment of physician's choice by an independent biostatistician using an interactive web-based system. Patients and investigators remained unmasked to treatment. Treatment of physician's choice was either capecitabine (1250 mg/m 2 orally twice per day on days 1-14) plus trastuzumab (8 mg/kg intravenously on day 1 then 6 mg/kg once per day) or capecitabine (1000 mg/m 2 ) plus lapatinib (1250 mg orally once per day on days 1-21), with a 21-day schedule. The primary endpoint, which was progression-free survival based on blinded independent central review, has previously been reported. PROs were assessed in the full analysis set (all patients randomly assigned to the study) using the oncology-specific European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), breast cancer-specific EORTC Quality of Life Questionnaire Breast 45 (QLQ-BR45), and the generic HRQoL EQ-5D-5L questionnaire. Analyses included change from baseline and time to definitive deterioration for PRO variables of interest and hospitalisation-related endpoints. This study is registered with ClinicalTrials.gov, NCT03523585, and is closed to recruitment., Findings: Between Sept 6, 2018, and Dec 31, 2020, 608 patients were randomly assigned to receive either trastuzumab deruxtecan (n=406; two did not receive treatment) or treatment of physician's choice (n=202; seven did not receive treatment). Overall, 603 patients (99%) were female and five (<1%) were male. The median follow-up was 21·5 months (IQR 15·2-28·4) in the trastuzumab deruxtecan group and 18·6 months (IQR 8·8-26·0) in the treatment of physician's choice group. Median treatment duration was 11·3 months (IQR 6·2-20·5) in the trastuzumab deruxtecan group and approximately 4·5 months in the treatment of physician's choice group (4·4 months [IQR 2·5-8·7] with trastuzumab; 4·6 months [2·1-8·9] with capecitabine; and 4·5 months [2·1-10·6] with lapatinib). Baseline EORTC QLQ-C30 global health status (GHS) scores were similar with trastuzumab deruxtecan (n=393) and treatment of physician's choice (n=187), and remained stable with no clinically meaningful change (defined as ≥10-point change from baseline) over time. Median time to definitive deterioration was delayed with trastuzumab deruxtecan compared with treatment of physician's choice for the primary PRO variable EORTC QLQ-C30 GHS (14·1 months [95% CI 10·4-18·7] vs 5·9 months [4·3-7·9]; HR 0·5573 [0·4376-0·7099], p<0·0001) and all other prespecified PROs (EORTC QLQ-C30 subscales, EORTC QLQ-BR45 arm and breast symptoms, and EQ-5D-5L visual analogue scale). Patient hospitalisation rates were similar in the trastuzumab deruxtecan (92 [23%] of 406) and treatment of physician's choice (41 [20%] of 202) groups; however, median time to hospitalisation was 133 days (IQR 56-237) with trastuzumab deruxtecan versus 83 days (30-152) with treatment of physician's choice., Interpretation: Overall, GHS and quality of life were maintained for both treatment groups, with prespecified PRO variables favouring trastuzumab deruxtecan over treatment of physician's choice, suggesting that despite a longer treatment duration, there was no detrimental impact on patient health-related quality of life with trastuzumab deruxtecan. When considered with efficacy and safety data from DESTINY-Breast02, these results support the overall benefit of trastuzumab deruxtecan for patients with HER2-positive unresectable or metastatic breast cancer previously treated with trastuzumab emtansine., Funding: Daiichi Sankyo and AstraZeneca., Competing Interests: Declaration of interests TF reports payments to their institution from Roche, Novartis, Pfizer, Daiichi Sankyo, MSD, and Eisai. FC, KD, and WL are full-time employees at Daiichi Sankyo. FA reports institutional research grants from Novartis, Pfizer, AstraZeneca, Eli Lilly, Daiichi Sankyo, and Roche, as well as consulting fees paid to their institution by MedImmune, Gilead, Relay Therapeutics, and Guardant Health. IK reports support for the present manuscript received by their institution from AstraZeneca and Daiichi Sankyo; grants to their institution from Pfizer, Macrogenics, and Genentech/Roche; consulting fees from AstraZeneca, Daiichi Sankyo, Genentech/Roche, Bristol Myers Squibb, Macrogenics, Taiho Oncology, and Seattle Genetics; honoraria from AstraZeneca; participation on a data safety monitoring or advisory board for Novartis and Merck; a leadership or fiduciary role in PureTech; and stock options in PureTech. YHP reports grants from MSD, Pfizer, Roche, AstraZeneca, Gencurix, NGeneBio, and Genome Insight; consulting fees from AstraZeneca, Pfizer, Eli Lilly, Bixink, MSD, Eisai, Roche, Daiichi Sankyo, Menarini, Gilead, and Novartis; payment for lectures, presentations, or educational events from AstraZeneca, Pfizer, Lilly, MSD, Roche, Daiichi Sankyo, and Novartis; support for attending meetings from Pfizer and Roche; participation on a data safety monitoring or advisory board for AstraZeneca, Pfizer, Roche, Gilead, and Novartis; and receipt of equipment or other services from Dong-A ST, Sanofi, Pfizer, and Roche. MDL reports payments for lectures or presentations from Eli Lilly, Novartis, Seagen, Takeda, Roche, Daiichi Sankyo, Tomalab, Gilead, Genetic, Menarini, and Sophos; support for attending meetings from Gilead, Novartis, Roche, and AstraZeneca; and participation on a data safety monitoring or advisory board for Pfizer, AstraZeneca, Sanofi, Seagen, Novartis, Ipsen, Roche, Pierre-Fabre, Daiichi Sankyo, and GSK. YM reports institutional grants from Daiichi Sankyo, Eisai, Chugai, MSD, Kyowa-Kirin, Eli Lilly, and Taiho; consulting fees from Daiichi Sankyo; and payments for lectures from Daiichi Sankyo, Chugai, Eisai, Eli Lilly, AstraZeneca, Pfizer, Taiho, and Kyowa-Kirin. AA reports institutional research funding from AstraZeneca; payment of advisory board fees from MSD, Gilead, AstraZeneca, and Roche; support for attending meetings from Novartis and Roche; and spousal shares from AstraZeneca. RY reports grants from Roche; consulting fees from Novartis, AstraZeneca, Eli Lilly, Roche, Medison, Pfizer, and Gilead; and payment for lectures or presentations from Novartis, AstraZeneca, Roche, Pfizer, and Eli Lilly. FPD reports grants from Fondation Belge Contre le Cancer; institutional payments from Roche, Pfizer, AstraZeneca, Eli Lilly, Novartis, Amgen, Daiichi Sankyo, Pierre-Fabre, Gilead, Seagen, and MSD; and support for attending meetings from Amgen, Roche, Teva, Pfizer, Daiichi Sankyo, AstraZeneca, Gilead, and MSD. TT reports payments for lectures from Daiichi Sankyo, Chugai, and Eli Lilly. AE is a full-time employee of Daiichi Sankyo and reports a restricted stock unit plan of Daiichi Sankyo Europe. S-BK reports institutional grants from Novartis, Sanofi, and DongKook Pharma; consulting fees from Novartis, AstraZeneca, Eli Lilly, Dae Hwa Pharm, ISU Abxis, and Daiichi Sankyo; payment for lectures from Novartis, AstraZeneca, Eli Lilly, Dae Hwa Pharm, ISU Abxis, and Daiichi Sankyo; a scientific co-chair role in ESMO Breast 2021–23 conferences; and stock in Genopeakes. MRB declares no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)