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Objective: The objective of this study was to explore patient preference for attributes of calcitonin gene‐related peptide (CGRP) inhibitors for the preventive treatment of migraine and to describe differences in treatment preferences between patients. Background: CGRP inhibitors are a novel class of migraine drugs specifically developed for the preventive treatment of migraine. Clinicians should understand patient preferences for CGRP inhibitors to inform and support prescribing choices. Methods: Patients with migraine in the US and Germany were recruited to participate in an online discrete choice experiment (DCE) survey, which presented hypothetical treatment choices using five attributes: mode of administration, side effects, migraine frequency, migraine severity, and consistency of treatment effectiveness. Attribute selection was informed by a literature review and semi‐structured patient interviews (n = 35), and evaluated using patient cognitive debriefing interviews (n = 5). Results: Of 680 who consented to participate, 506 participants completed the survey and were included in the study (US = 257; Germany = 249). Overall, participants placed highest importance (preference weight, beta = 1.65, p < 0.001) on the treatment's ability to reduce the severity of migraine (mild vs. unchanged severity), followed by consistent treatment effectiveness (beta = 1.13, p < 0.001), and higher chance of reduced migraine frequency (beta = 1.00, p < 0.001). Participants preferred an oral tablet every other day (beta = 1.00, p < 0.001) over quarterly infusion, quarterly injections (p = 0.019), or monthly injection (p < 0.001). Preference for all treatment attributes were heterogeneous, and the subgroup analyses found that participants naïve to CGRP monoclonal antibody treatments had a stronger preference for oral therapy compared to those with such experience (p = 0.006). Conclusion: In this DCE assessing CGRP inhibitors attributes, the main driver of patient choice was treatment effectiveness, specifically reduced migraine severity, and consistent treatment effectiveness. Further, patients exhibited an overall preference for an oral tablet every other day over injectables. Patients' experience with previous treatments informs the value they place on treatment characteristics. [ABSTRACT FROM AUTHOR]

We examine upper mantle anisotropy across the Antarctic continent using 102 new shear wave splitting measurements obtained from teleseismic SKS, SKKS, and PKS phases combined with 107 previously published results. For the new measurements, an eigenvalue technique is used to estimate the fast polarization direction and delay time for each phase arrival, and high‐quality measurements are stacked to determine the best‐fit splitting parameters at each seismic station. The ensemble of splitting measurements shows largely NE‐SW‐oriented fast polarization directions across Antarctica, with a broadly clockwise rotation in polarization directions evident moving from west to east across the continent. Although the first‐order pattern of NE‐SW‐oriented polarization directions is suggestive of a single plate‐wide source of anisotropy, we argue the observed pattern of anisotropy more likely arises from regionally variable contributions of both lithospheric and sub‐lithospheric mantle sources. Anisotropy observed in the interior of East Antarctica, a region underlain by thick lithosphere, can be attributed to relict fabrics associated with Precambrian tectonism. In contrast, anisotropy observed in coastal East Antarctica, the Transantarctic Mountains (TAM), and across much of West Antarctica likely reflects both lithospheric and sub‐lithospheric mantle fabrics. While sub‐lithospheric mantle fabrics are best associated with either plate motion‐induced asthenospheric flow or small‐scale convection, lithospheric mantle fabrics in coastal East Antarctica, the TAM, and West Antarctica generally reflect Jurassic—Cenozoic tectonic activity. Plain Language Summary: Seismic anisotropy, the directionally dependent variation in seismic wave speed, is widely considered to be one of the best indicators of past and present deformation and flow in the upper mantle. When the mantle deforms or flows, olivine crystals often become oriented in a systematic direction. Measurements of seismic anisotropy delineate the direction in which olivine crystals in the upper mantle are aligned and provide useful information about the tectonic history and current mantle flow in a region. In this study, we use seismic waves from distant earthquakes recorded at seismometers located in Antarctica to measure upper mantle anisotropy. Our measurements generally indicate that seismic waves travel the fastest in a northeasterly southwesterly direction in the upper mantle across much of Antarctica. The relatively uniform seismic anisotropy that we measure across Antarctica is suggestive of a single source of origin; however, we conclude that the observed anisotropy must arise from several sources, including past tectonic activity and active mantle flow beneath Antarctica. Key Points: One hundred two new and revised shear wave splitting measurements using teleseismic SKS, SKKS, and PKS phases are reportedPredominantly Grid northeast‐southwest oriented fast polarization directions are found across AntarcticaAnisotropy can be attributed to relict lithospheric fabrics, plate motion‐induced asthenospheric flow, and small‐scale convection [ABSTRACT FROM AUTHOR]

We have located 117 previously undetected seismic events mainly occurring between 2015 and 2017 that originated from glacial, tectonic, and volcanic processes in central West Antarctica using data recorded on Polar Earth Observing Network (POLENET/ANET) and UK Antarctic Network (UKANET) seismic stations. The seismic events, with local magnitudes (ML) ranging from 1.1 to 3.5, are predominantly clustered in four geographic regions; the Ellsworth Mountains, Thwaites Glacier, Pine Island Glacier, and Mount Takahe. Eighteen of the events are in the Ellsworth Mountains and can be attributed to a mixture of glacial and tectonic processes. The largest event noted in this study was a mid‐crustal (∼19 km focal depth; ML 3.5) normal mechanism earthquake beneath Thwaites Glacier. We also located 91 glacial events near the grounding zones of Thwaites Glacier and Pine Island Glacier that are predominantly associated with time periods of significant calving activity. Eight events, likely arising from volcano‐tectonic processes, occurred beneath Mount Takahe. Using Pn travel times from the seismic events, we find laterally variable uppermost mantle structure in central West Antarctica. On average, the Ellsworth Mountains are underlain by a faster mantle lid (VPn = ∼8.4 km/s) compared to the Amundsen Sea Embayment region (VPn = ∼8.1 km/s). Within the Amundsen Sea Embayment itself, we find mantle lid velocities ranging from ∼8.05 to 8.18 km/s. Laterally heterogeneous uppermost mantle structure, indicative of variable thermal and rheological structure, likely influences both geothermal heat flux and glacial isostatic adjustment spatial patterns and rates within central West Antarctica. Plain Language Summary: In this study, we have identified and located 117 seismic events in central West Antarctica. The seismic events originate from both solid‐Earth and glacial processes. While the seismic events originating from solid‐Earth processes are associated with tectonic and volcano‐tectonic activity in central West Antarctica, the seismic events arising from glacial processes are predominantly associated with time periods of significant calving activity at Thwaites Glacier and Pine Island Glacier. Using select P‐waves produced by seismic events located in this study, we investigate the uppermost portion of the mantle beneath central West Antarctica and find that the temperature of the uppermost mantle likely varies by at least 160 K across central West Antarctica. Variable uppermost mantle temperatures have numerous implications for the dynamics and evolution of the West Antarctic Ice Sheet. Key Points: Located 117 previously undetected seismic events of glacial, tectonic, and volcano‐tectonic originLaterally variable Pn velocity structure across central West Antarctica [ABSTRACT FROM AUTHOR]

The geothermal heat flux (GHF) is an important boundary condition for modeling the movement of the Antarctic ice sheet but is difficult to measure systematically at a continental scale. Earlier GHF maps suffer from low resolution and possibly biased assumptions in tectonism and crustal heat generation, resulting in significant uncertainty. We present a new GHF map for Antarctica constructed by empirically relating the upper mantle structure to known GHF in the continental United States. The new map, compared with previously seismologically determined one, has improved resolution and lower uncertainties. New features in this map include high GHF in the southern Transantarctic Mountains where warmer uppermost mantle is introduced by lithospheric removal and in the Thwaites Glacier region. Additionally, a modest GHF in the central West Antarctic Rift system near the Siple Coast and an absence of large‐scale regions with GHF greater than 90 mW/m2 are found. Plain Language Summary: The flow of the heat from Earth's interior into the ice sheet of Antarctica, or geothermal heat flux, has been poorly constrained but is important for understanding the movement of the ice sheet. In this study, we present a new map of the geothermal heat flux estimated from the latest studies of the seismic structure of Antarctica. This is accomplished by directly relating seismic wave speeds with heat flux for the continental United States, a place where many local heat flux measurements have been collected. The new map contains features that have not been reported before. For example, we find that more heat is coming out from the base of the southern Transantarctic Mountains, which is perhaps related to the missing thick and cold lithosphere beneath that region. We also report that part of West Antarctica may have lower geothermal heat flux than previously reported. The new map will help model the movement of the Antarctic ice sheet and predict its future. Key Points: A new geothermal heat flux map for the continental Antarctica is presentedBased on the latest seismic structure of Antarctica, the new map has improved resolution and reduced uncertaintiesNew features of the map include high GHF in the Thwaites Glacial region and southern Transantarctic Mountains [ABSTRACT FROM AUTHOR]

Aim Quality of life weights (utilities) are an important input in economic evaluation and evidence suggests that there can be important differences between countries. This study was designed to capture utilities for metastatic non-small cell lung cancer and common grade III/IV toxicities associated with treatment from local populations in the United Kingdom, Australia, France, China, Taiwan, and Korea. Toxicities included neutropenia, febrile neutropenia, fatigue, diarrhea, nausea and vomiting, rash, bleeding, hypertension, and hair loss. Methods Existing health state descriptions of non-small cell lung cancer were adapted to represent descriptions of patients on first-line treatment. Twenty-three states were translated and assessed in cognitive debrief content validation interviews with oncologists in each country. Seventy-five respondents per country completed a time trade-off interview to evaluate the states. Variation between countries for all states was explored with a Generalized Estimating Equations model. Results The mean utility for 'stable disease and no side effects' (base state) varied between 0.84 (United Kingdom) and 0.54 (Taiwan). The largest utility decrements were found for febrile neutropenia (0.47) and neutropenia (0.35) across all countries. Asian countries regarded bleeds as a severe toxicity whereas non-Asian countries did not and valued diarrhea and fatigue as more severe. Significant differences in utilities between countries emerged with the Taiwanese population in particular rating states as significantly worse than other countries. Conclusion This study improves our understanding of how utilities for the same states can vary across countries. The study shows the importance of capturing utilities that reflect the preferences of the local population. [ABSTRACT FROM AUTHOR]

Background: The treatment of common bile duct stones discovered at routine intraoperative cholangiography includes postoperative endoscopic retrograde cholangiography or intraoperative laparoscopic common bile duct exploration. Given the equivalence of short-term outcome data for these two techniques, the choice of one over the other may be influenced by long-term follow-up data. We aimed to establish the long-term outcomes following laparoscopic common bile duct exploration and compare this with endoscopic retrograde cholangiography. Methods: One hundred and fifty consecutive patients underwent laparoscopic common bile duct exploration between March 1998 and March 2006 carried out by a single surgeon. All were prospectively studied for 1 month followed by a late-term phone questionnaire ascertaining the prevalence of adverse symptoms. Patients presented with a standardized series of questions, with reports of symptoms corroborated by review of medical records. Results: In 150 patients, operations included laparoscopic transcystic exploration (135), choledochotomy (10) and choledochoduodenostomy (2). At long-term follow up (mean 63 months), 116 (77.3%) patients were traceable, with 24 (20.7%) reporting an episode of pain and 18 (15.5%) had more than a single episode of pain. There was no long-term evidence of cholangitis, stricture or pancreatitis identified in any patient. Conclusion: Laparoscopic bile duct exploration appears not to increase the incidence of long-term adverse sequelae beyond the reported prevalence of postcholecystectomy symptoms. There was no incidence of bile duct stricture, cholangitis or pancreatitis. It is a safe procedure, which obviates the need and expense of preoperative or postoperative endoscopic retrograde cholangiography in most instances. [ABSTRACT FROM AUTHOR]