Erosion and Accretion Trends of New Hampshire Beaches from December 2016 to March 2020: Results of the Volunteer Beach Profile Monitoring Program

New Hampshire Atlantic beaches were monitored from December 2016 to March 2020 to determine seasonal changes in morphology and elevation, assess the response of the beaches to storms with respect to erosion and subsequent recovery, and develop a baseline to determine long-term trends in beach size, elevation, and position. A unique aspect of this study was the involvement of community volunteers working together with the University of New Hampshire (UNH) Center for Coastal and Ocean Mapping, UNH Cooperative Extension, New Hampshire Sea Grant, and the New Hampshire Geological Survey. The monitoring network consisted of thirteen stations located at six of the major beaches, including each of the state beaches. Monitoring stations were located at Wallis Sands, Jenness Beach, North Hampton Beach, North Beach, Hampton Beach, and Seabrook Beach. At least two stations were located at each beach (Seabrook Beach had three stations). Beach elevation profiles were run routinely at each station at approximately three- to four-week intervals. Additional measurements were made following several major storms. In total, approximately 400 elevation profiles were run at the thirteen stations. The elevation profiles were run using the Emery (1961) method which utilizes two calibrated rods and the horizon for leveling. Sediment volume calculations were made for each profile that approximated the amount of material in the intertidal zone for that profile at that point in time for a one-meter wide swath of the beach. Seasonal changes and storm impacts on beach elevations, profile characteristics, and sediment volumes are discussed in detail for each beach and the major conditions and processes that control their stability discussed

Inhibition of dual-specificity tyrosine phosphorylation-regulated kinase 2 perturbs 26S proteasome-addicted neoplastic progression

Dependence on the 26S proteasome is an Achilles' heel for triple-negative breast cancer (TNBC) and multiple myeloma (MM). The therapeutic proteasome inhibitor, bortezomib, successfully targets MM but often leads to drug-resistant disease relapse and fails in breast cancer. Here we show that a 26S proteasome-regulating kinase, DYRK2, is a therapeutic target for both MM and TNBC. Genome editing or small-molecule mediated inhibition of DYRK2 significantly reduces 26S proteasome activity, bypasses bortezomib resistance, and dramatically delays in vivo tumor growth in MM and TNBC thereby promoting survival. We further characterized the ability of LDN192960, a potent and selective DYRK2-inhibitor, to alleviate tumor burden in vivo. The drug docks into the active site of DYRK2 and partially inhibits all 3 core peptidase activities of the proteasome. Our results suggest that targeting 26S proteasome regulators will pave the way for therapeutic strategies in MM and TNBC

Ixazomib-lenalidomide-dexamethasone in routine clinical practice: Effectiveness in relapsed/refractory multiple myeloma

[Aim]: To evaluate the effectiveness and safety of ixazomib-lenalidomide-dexamethasone (IRd) in relapsed/refractory multiple myeloma in routine clinical practice. Patients & methods: Patient-level data from the global, observational INSIGHT MM and the Czech Registry of Monoclonal Gammopathies were integrated and analyzed.[Results]: At data cut-off, 263 patients from 13 countries were included. Median time from diagnosis to start of IRd was 35.8 months; median duration of follow-up was 14.8 months. Overall response rate was 73%, median progression-free survival, 21.2 months and time-to-next therapy, 33.0 months. Ixazomib/lenalidomide dose reductions were required in 17%/36% of patients; 32%/30% of patients discontinued ixazomib/lenalidomide due to adverse events.[Conclusion]: The effectiveness and safety of IRd in routine clinical practice are comparable to those reported in TOURMALINE-MM1.This work was supported by Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited

Rates of Influenza and Pneumococcal Vaccination and Correlation With Survival in Multiple Myeloma Patients

[Background]: Infections are a common reason for hospitalization and death in multiple myeloma (MM). Although pneumococcal vaccination (PV) and influenza vaccination (FV) are recommended for MM patients, data on vaccination status and outcomes are limited in MM.[Materials and Methods]: We utilized data from the global, prospective, observational INSIGHT MM study to analyze FV and PV rates and associated outcomes of patients with MM enrolled 2016-2019.[Results]: Of the 4307 patients enrolled, 2543 and 2500 had study-entry data on FV and PV status. Overall vaccination rates were low (FV 39.6%, PV 30.2%) and varied by region. On separate multivariable analyses of overall survival (OS) by Cox model, FV in the prior 2 years and PV in the prior 5 years impacted OS (vs. no vaccination; FV: HR, 0.73; 95% CI, 0.60-0.90; P = .003; PV: HR, 0.51; 95% CI, 0.42-0.63; P < .0001) when adjusted for age, region, performance status, disease stage, cytogenetics at diagnosis, MM symptoms, disease status, time since diagnosis, and prior transplant. Proportions of deaths due to infections were lower among vaccinated versus non-vaccinated patients (FV: 9.8% vs. 15.3%, P = .142; PV: 9.9% vs. 18.0%, P = .032). Patients with FV had generally lower health resource utilization (HRU) versus patients without FV; patients with PV had higher or similar HRU versus patients without PV.[Conclusion]: Vaccination is important in MM and should be encouraged. Vaccination status should be recorded in prospective clinical trials as it may affect survival. This trial was registered at www.clinicaltrials.gov as #NCT02761187.This study was sponsored by Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.Peer reviewe

Effects of social media on adolescents’ willingness and intention to use e-cigarettes: An experimental investigation

IntroductionThis study examined the effects of experimentally manipulated social media exposure on adolescents' willingness and intention to use e-cigarettes.Aims and methodsParticipants were 135 adolescents of age 13-18 (52.6% female, mean age = 15.3) in California. Participants viewed six social media posts online in a 2 (post source: peer or advertisement) × 2 (e-cigarette content exposure: heavy or light) between-subjects design. Analyses were weighted to population benchmarks. We examined adolescents' beliefs, willingness, and intention to use e-cigarettes in association with social media use intensity in daily life and with experimentally manipulated exposure to social media posts that varied by source (peer or advertisement) and content (e-cigarette heavy or light).ResultsGreater social media use in daily life was associated with greater willingness and intention to use e-cigarettes and more positive attitudes, greater perceived norms, and lower perceived danger of e-cigarette use (all p-values &lt;.01). In tests of the experimental exposures, heavy (vs. light) e-cigarette content resulted in greater intention (p = .049) to use e-cigarettes and more positive attitudes (p = .019). Viewing advertisements (vs. peer-generated posts) resulted in greater willingness and intention (p-values &lt;.01) to use e-cigarettes, more positive attitudes (p = .003), and greater norm perceptions (p = .009). The interaction effect of post source by post content was not significant for any of the outcomes (all p-values &gt;.529).ConclusionsGreater social media use and heavier exposure to advertisements and e-cigarette content in social media posts are associated with a greater risk for e-cigarette use among adolescents. Regulatory action is needed to prohibit sponsored e-cigarette content on social media platforms used by youth.ImplicationsAdolescents who use social media intensely may be at higher risk for e-cigarette use. Even brief exposure to e-cigarette content on social media was associated with greater intention to use and more positive attitudes toward e-cigarettes. Regulatory action should be taken to prohibit sponsored e-cigarette content on social media used by young people, including posts by influencers who appeal to young people

Management of patients with multiple myeloma beyond the clinical-trial setting: understanding the balance between efficacy, safety and tolerability, and quality of life.

Treatment options in multiple myeloma (MM) are increasing with the introduction of complex multi-novel-agent-based regimens investigated in randomized clinical trials. However, application in the real-world setting, including feasibility of and adherence to these regimens, may be limited due to varying patient-, treatment-, and disease-related factors. Furthermore, approximately 40% of real-world MM patients do not meet the criteria for phase 3 studies on which approvals are based, resulting in a lack of representative phase 3 data for these patients. Therefore, treatment decisions must be tailored based on additional considerations beyond clinical trial efficacy and safety, such as treatment feasibility (including frequency of clinic/hospital attendance), tolerability, effects on quality of life (QoL), and impact of comorbidities. There are multiple factors of importance to real-world MM patients, including disease symptoms, treatment burden and toxicities, ability to participate in daily activities, financial burden, access to treatment and treatment centers, and convenience of treatment. All of these factors are drivers of QoL and treatment satisfaction/compliance. Importantly, given the heterogeneity of MM, individual patients may have different perspectives regarding the most relevant considerations and goals of their treatment. Patient perspectives/goals may also change as they move through their treatment course. Thus, the 'efficacy' of treatment means different things to different patients, and treatment decision-making in the context of personalized medicine must be guided by an individual's composite definition of what constitutes the best treatment choice. This review summarizes the various factors of importance and practical issues that must be considered when determining real-world treatment choices. It assesses the current instruments, methodologies, and recent initiatives for analyzing the MM patient experience. Finally, it suggests options for enhancing data collection on patients and treatments to provide a more holistic definition of the effectiveness of a regimen in the real-world setting

Management of patients with multiple myeloma beyond the clinical-trial setting: understanding the balance between efficacy, safety and tolerability, and quality of life

Treatment options in multiple myeloma (MM) are increasing with the introduction of complex multi-novel-agent-based regimens investigated in randomized clinical trials. However, application in the real-world setting, including feasibility of and adherence to these regimens, may be limited due to varying patient-, treatment-, and disease-related factors. Furthermore, approximately 40% of real-world MM patients do not meet the criteria for phase 3 studies on which approvals are based, resulting in a lack of representative phase 3 data for these patients. Therefore, treatment decisions must be tailored based on additional considerations beyond clinical trial efficacy and safety, such as treatment feasibility (including frequency of clinic/hospital attendance), tolerability, effects on quality of life (QoL), and impact of comorbidities. There are multiple factors of importance to real-world MM patients, including disease symptoms, treatment burden and toxicities, ability to participate in daily activities, financial burden, access to treatment and treatment centers, and convenience of treatment. All of these factors are drivers of QoL and treatment satisfaction/compliance. Importantly, given the heterogeneity of MM, individual patients may have different perspectives regarding the most relevant considerations and goals of their treatment. Patient perspectives/goals may also change as they move through their treatment course. Thus, the ‘efficacy’ of treatment means different things to different patients, and treatment decision-making in the context of personalized medicine must be guided by an individual’s composite definition of what constitutes the best treatment choice. This review summarizes the various factors of importance and practical issues that must be considered when determining real-world treatment choices. It assesses the current instruments, methodologies, and recent initiatives for analyzing the MM patient experience. Finally, it suggests options for enhancing data collection on patients and treatments to provide a more holistic definition of the effectiveness of a regimen in the real-world setting