Hokusai
51882483
Clinical Impact of Bleeding in Cancer Associated Venous Thromboembolism: Results from the Hokusai VTE Cancer Study.
In the Hokusai VTE Cancer study, edoxaban was non inferior to dalteparin for the composite outcome of recurrent venous thromboembolism (VTE) and major bleeding in 1,050 patients with cancer associated VTE. The absolute rate of recurrent VTE was 3.4% lower with edoxaban, whereas the absolute rate of major bleeding was 2.9% higher. The present analysis focuses on the sites, clinical presentation, course and outcome of bleeding events, and the associated tumour types. Major bleeds and their severity (categories 1 4) were blindly adjudicated by a committee using a priori defined criteria, and data were analysed in the safety population. Major bleeding occurred in 32 of 522 patients given edoxaban (median treatment duration, 211 days) and in 16 of 524 patients treated with dalteparin (median treatment duration, 184 days) no patients had more than one major bleed. There were no fatal bleeds with edoxaban, and two with dalteparin. Severe bleeding at presentation (category 3 or 4) occurred in 10 (1.9% and 11 (2.1% patients in the edoxaban and dalteparin groups, respectively. The excess of major bleeding with edoxaban was confined to patients with gastrointestinal cancer. However, severe major bleeding at presentation (category 3 or 4) in this sub group occurred in 5 of 165 (3.0% and in 3 of 140 (2.1% patients given edoxaban or dalteparin, respectively.In conclusion, this analysis suggests that while oral edoxaban is an appropriate alternative to subcutaneous dalteparin for treatment of cancer associated VTE, the use of edoxaban in patients with gastrointestinal cancer requires careful benefit risk weighting.
Thrombosis and haemostasis
Noemie Kraaijpoel Marcello Di Nisio Frits I Mulder Nick van Es Jan Beyer-Westendorf Marc Carrier David A Garcia Michael A Grosso Ajay K Kakkar Michele F Mercuri Saskia Middeldorp Cristhiam Rojas Hernandez Amparo Santamaria Lee Schwocho Annelise Segers Peter Verhamme Tzu-Fei Wang Jeffrey I Weitz George Zhang Jeffrey I Zwicker Harry R Buller Gary E Raskob
195805459
Extended treatment with edoxaban in cancer patients with venous thromboembolism: A post hoc analysis of the Hokusai VTE Cancer study
Patients with active cancer and venous thromboembolism (VTE) are at high risk of recurrence. Therefore, continued anticoagulant therapy beyond the initial 6 months is suggested in this patient population, but evidence supporting this approach is limited.
Journal of thrombosis and haemostasis JTH
Marcello Di Nisio Nick van Es Marc Carrier Tzu-Fei Wang David A Garcia Annelise Segers Jeffrey I Weitz Harry R Buller Gary E Raskob
73447001
Determinants of the Quality of Warfarin Control after Venous Thromboembolism and Validation of the SAMe TT2 R2 Score: An Analysis of Hokusai VTE.
BACKGROUND Time in therapeutic range (TTR) measures the quality of vitamin K antagonist (VKA) anticoagulation. In patients with atrial fibrillation, the dichotomized SAMe TT2 R2 score =2 vs. 2 points) can predict if adequate TTR is unlikely to be achieved. AIMS We validated the SAMe TT2 R2 score in patients with venous thromboembolism (VTE) randomized to the warfarin arm of the Hokusai VTE trial. PATIENTS AND METHODS A total of 3,874 patients were included in the primary analysis (day 31 180 from randomization) The efficacy and safety outcomes were symptomatic recurrent VTE and major or clinically relevant non major bleeding. RESULTS The rates of recurrent VTE and bleeding events were higher in patients with a TTR below the median 66% vs. =66% resulting in an absolute risk difference (ARD) of +0.5% (95% confidence interval: 0% +1.1% and +2.2% (0.9% +3.5% respectively. Patients with high SAMe TT2 R2 score were 76% of total and had lower median TTR (64.7% vs. 70.7% The SAMe TT2 R2 score exhibited low negative (0.59) and positive (0.52) predictive value (TTR threshold 66% and poor discrimination (c statistic, 0.58) ARD between patients with high and low score was 0% 0.6% +0.7% for recurrence and +1.3% 0.1% +2.7% for bleeding. Results were confirmed in sensitivity analyses focusing on the whole study period (day 1 365) CONCLUSION In VTE patients, the SAMe TT2 R2 score showed unsatisfactory discrimination and predictive value for individual TTR and did not correlate well with clinical outcomes. The choice of starting a patient on VKA cannot be based on this parameter and its routine use after VTE may not translate into clinical usefulness.
Thrombosis and haemostasis
Stefano Barco Serena Granziera Michiel Coppens Jonathan Douxfils Mathilde Nijkeuter Nicoletta Riva Thomas Vanassche George Zhang Min Lin Pieter Willem Kamphuisen Alexander T Cohen Jan Beyer-Westendorf
197564755
Geology of the Hokusai quadrangle (H05) Mercury
ABSTRACT The Hokusai (H05) quadrangle is in Mercury's northern mid latitudes (0 90degE, 22.5 65degN) and covers almost 5 million km2, or 6.5% of the planet's surface. We have used data from the MESSENGER spacecraft to make the first geological map of H05. Linework was digitized at 1:400,000 scale for final presentation at 1:3,000,000 scale, mainly using a ~166 m/pixel monochrome basemap. Three major photogeologic units of regional extent were mapped: intercrater, intermediate, and smooth plains. Materials of craters 20 km in diameter were classified according to their degradation state. Two classification schemes were employed in parallel, one with three classes and the other with five classes, for compatibility with existing MESSENGER era quadrangle maps and the first global geologic map. This map will provide science context and targets for the ESA JAXA BepiColombo mission to Mercury.
Journal of Maps
Jack Wright David A Rothery Matthew R Balme Susan J Conway
203439120
Evidence of early amorphous arsenic sulfide production and use in Edo period Japanese woodblock prints by Hokusai and Kunisada
This study explores the evolution of the manufacturing process of artificial arsenic sulfide pigments in Edo period Japan through the analysis of three impressions of the same print dated from the 1830s and attributed to Katsushika Hokusai (1760 1849) and one from 1852 and attributed to Utagawa Kunisada (1786 1865) Colorants in the yellow and green areas of the four prints were investigated by means of non invasive and microanalytical techniques such as optical microscopy, fiber optic reflectance spectroscopy and Raman spectroscopy. While the pigments in the green and yellow areas are similar throughout the set of prints Prussian blue, indigo (for the Hokusai prints) and orpiment were identified optical microscopy and Raman spectroscopy highlighted some variations in the orpiment used in the green areas of the prints. Two of the Hokusai prints present bright yellow particles of larger size and lamellar morphology, identified by Raman spectroscopy as natural orpiment. The third print presents an admixture of bright yellow natural orpiment particles with a smaller number of orange yellow particles shown by Raman to be partially amorphous arsenic sulfide. Small bright yellow particles identified as fully amorphous arsenic sulfide pigments by Raman were found throughout the green areas of the Kunisada print. Although supported by Japanese historical sources, local production of artificial arsenic sulfide in the early nineteenth century was not previously documented. The simultaneous presence of both crystalline and amorphous domains in a single pigment particle in some of the Hokusai prints suggests that natural orpiment was used as primary source of arsenic for the production of a low grade artificial pigment. The pigment found in the Kunisada print, by contrast, was obtained from arsenic oxide (or arsenolite) and sulfur though a dry process synthesis, as shown by the sulfur excess, signs of heat treatments and fully amorphous nature of the pigment. These findings set the earliest dates for both the ore sublimation process and the arsenolite dry process, and are of foremost importance to understand the evolution of the amorphous arsenic sulfide production in Edo period Japan and its introduction in the palette of Japanese woodblock prints.
Heritage Science
Marc Vermeulen Marco Leona
202669977
Treatment of Cancer Associated Thrombosis: Beyond HOKUSAI
Direct oral anticoagulants (DOACs) represent an attractive alternative to low molecular weight heparins (LMWHs) for the long term treatment of cancer associated thrombosis (CT) since they avoid the burden of daily injections. Analyses in subgroups of cancer patients from large randomized trials suggested that DOACs were at least as effective as vitamin K antagonists, while indirect comparisons suggested that DOACs' efficacy and safety profile were comparable to those of LMWHs. In the randomized controlled HOKUSAI VTE Cancer study, currently the only completed phase III trial on DOACs in CT patients, edoxaban was shown noninferior to dalteparin on the composite primary endpoint of time to first recurrent venous thromboembolism or major bleeding during the 12 months after randomization. Study results suggest that both agents had comparable benefit/risk ratio in patients with CT. Even though this conclusion was valid from a strict statistical viewpoint, it was potentially misleading when interpreting benefit/risk ratios. Besides the obvious heterogeneity of the study population (e.g. 23% of patients no longer had cancer) and significantly different treatment durations between arms, secondary outcomes for efficacy were in favor of edoxaban for recurrent deep vein thrombosis but not for recurrent pulmonary embolism, and major bleeding episodes were significantly more frequent in the edoxaban group, with an excess of gastrointestinal (GI) bleeding episodes observed mainly but not only in patients with GI cancers. More research is needed regarding specific patients' profiles, cancer types, and treatment period to better clarify the respective roles of DOACs and LMWHs in CT patients.
TH open companion journal to thrombosis and haemostasis
Isabelle Mahe Ismail Elalamy Grigoris T Gerotziafas Philippe Girard
85457849
Developing a systematic approach to determine the sequence of impressions of Japanese woodblock prints: the case of Hokusai's 'Red Fuji'
Ukiyo e Japanese woodblock prints were mass produced in the Edo Period and early impressions of a given print are generally of higher quality and more sought after by connoisseurs than late impressions. The present publication presents an innovative approach that combines the classical method of examining line quality with a systematic study of colourants. This approach was used to compare an impression of Hokusai's iconic 'Red Fuji' with its rare variant, 'Pink Fuji' Woodblock wear and printing effects were studied using high resolution photographs and the colourants were characterised using non destructive methods. Signs of greater woodblock wear were identified in 'Red Fuji' compared to 'Pink Fuji' and there were indications that much more thought had been given to the selection and application of the colourants in 'Pink Fuji' This showed that 'Pink Fuji' was printed before 'Red Fuji' and is possibly a first edition. The approach developed here represents a novel way of studying Japanese woodblock prints and can be used to determine the sequence of impressions of other prints.
Heritage Science
Capucine F Korenberg Lucia Pereira-Pardo Peter J McElhinney Joanne Dyer
208086981
Edoxaban for treatment of venous thromboembolism in patient groups with different types of cancer: Results from the Hokusai VTE Cancer study.
BACKGROUND The safety and efficacy of edoxaban and dalteparin is unclear for several cancer groups. METHODS We evaluated the occurrence of the primary outcome in large cancer groups. The primary outcome was the composite of recurrent VTE or major bleeding over 12 months. RESULTS In patients with gastrointestinal cancer, the primary outcome occurred in 19.4% patients given edoxaban and in 15.0% given dalteparin (risk difference [RD] 4.4% 95% CI, 4.1% to 12.8% The corresponding rates for edoxaban and dalteparin were 10.4% and 10.7% for lung cancer (RD, 0.3% 95% CI, 10.0% to 9.5% 13.6% and 12.5% for urogenital cancer (RD, 1.1; 95% CI, 10.1 12.4) 3.1% and 11.7% for breast cancer (RD, 8.6; 95% CI, 19.3 2.2) 8.9% and 10.9% for hematological malignancies (RD, 2.0; 95% CI, 13.1 9.1) and 10.4% and 17.4% for gynecological cancer (RD, 7.0; 95% CI, 19.8 5.7) In the subgroup of gastrointestinal cancer, edoxaban was associated with a 3.5% lower absolute risk of recurrent VTE and a 7.9% higher risk of major bleeding. CONCLUSION Edoxaban has a similar risk benefit ratio to dalteparin in most cancer groups. In those with gastrointestinal cancer, the lower risk of recurrent VTE and the advantages of oral therapy need to be balanced against the increased risk of major bleeding.
Thrombosis research
Frits I Mulder Nick van Es Noemie Kraaijpoel Marcello Di Nisio Marc Carrier Anil Duggal Manila Gaddh David A Garcia Michael A Grosso Ajay Kakkar M Mercuri Saskia Middeldorp Gordon Royle Annelise Segers Sudeep P Shivakumar Peter Verhamme T Wang Jeffrey I Weitz G Zhang Harry R Buller Gary E Raskob
202905951
MESSENGER Observations of Volcanism on Mercury: From Hokusai Quadrangle Down to Small Cones
This thesis addresses the regional geology of the planet Mercury as seen by the MErcury Surface, Space ENvironment, and Ranging (MESSENGER) mission. I aimed to investigate the existence and origin of volcanic photogeological units and landforms on Mercury not mappable at the global scale. Using MESSENGER images, I have made the first 1:3,000,000 scale geological map of the Hokusai (H05) quadrangle. My map shows that this region has a similar history of effusive volcanism to the rest of Mercury, with widespread plains formation having given way to lower volume effusions that were ultimately confined to impact craters. However, I found that H05 contains plains that do not conform to the definitions of the two globally recognised plains units on Mercury, intercrater plains and smooth plains, which are thought to be volcanic in origin. I mapped such plains as intermediate plains, due to their intermediate roughness between the two global plains types, and I suggest that they represent incompletely volcanically resurfaced regions of Mercury's crust. The apparent absence of even small volcanic constructs on Mercury, emphasised to me during my mapping of the volcanologically diverse H05, led me to search for such constructs across Mercury. The two candidates I found, if volcanic, were probably built by low volume eruptions that were uncharacteristic of most of Mercury's volcanic history. During my search for volcanoes, I investigated the circum Caloris knobs. Through mapping, photogeological observations and topographic measurements, I have shown that these small <15 km across) landforms are not volcanoes, but instead are Caloris ejecta blocks that have undergone long lived, or even recent, modification into cones. My observations suggest that volatile loss might have driven modification of the blocks. The intermediate plains, candidate volcanoes, and circum Caloris knobs will be important targets for the BepiColombo mission, which launched during the preparation of this thesis.
Jack Wright
218542663
Artist Spotlight: Robert Bosch: Opt emoji Hokusai
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