Mesoscale eddies play a central role in the poleward oceanic heat flux in the Southern Ocean.Previous studies have documented changes in the location of temperature fronts in the Southern Ocean,but little attention ha...Mesoscale eddies play a central role in the poleward oceanic heat flux in the Southern Ocean.Previous studies have documented changes in the location of temperature fronts in the Southern Ocean,but little attention has been paid to changes in the genesis locations of mesoscale eddies.Here,we provide evidence from three decades of satellite altimetry observations for the heterogeneity of the poleward shift of mesoscale activities,with the largest trend of~0.23°±0.05°(10 yr)^(-1) over the Atlantic sector and a moderate trend of~0.1°±0.03°(10 yr)^(-1) over the Indian sector,but no significant trend in the Pacific sector.The poleward shift of mesoscale eddies is associated with a southward shift of the local westerly winds while being constrained by the major topographies.As the poleward shift of westerly winds is projected to persist,the poleward oceanic heat flux from mesoscale eddies may influence future ice melt.展开更多
Ivosidenib,an isocitrate dehydrogenase 1(IDH1)inhibitor,has demonstrated clinical benefits in a pivotal study(AG120-C-001)in patients with IDH1-mutated(mIDH1)acute myeloid leukemia(AML).A registry study(CS3010-101:NCT...Ivosidenib,an isocitrate dehydrogenase 1(IDH1)inhibitor,has demonstrated clinical benefits in a pivotal study(AG120-C-001)in patients with IDH1-mutated(mIDH1)acute myeloid leukemia(AML).A registry study(CS3010-101:NCT04176393)was conducted to assess the pharmacokinetic(PK)characteristics,safety,and efficacy of ivosidenib in Chinese patients with relapsed or refractory(R/R)mIDH1 AML.Patients received ivosidenib 500 mg once daily for 28-day cycles until disease progression.Ten subjects underwent intensive PK/progressive disease(PD)assessments.All subjects had the clinical response assessed at screening,every 28 days through month 12,and then every 56 days.Between November 12,2019,and April 2,2021,30 patients were enrolled;26(86.7%)had de novo AML and 18(60.0%)were transfusion-dependent at baseline.Following single and repeated doses of ivosidenib,median time to maximum plasma concentration(T_(max))was 4.0 and 2.0 hours,respectively.The inter-individual variability of pharmacokinetic exposure was moderate to high(coefficient of variation[CV],25%–53%).No obvious accumulation was observed after repeated doses at cycle 2 day 1.Regarding the clinical response,the CR+CRh rate was 36.7%(95%confidence interval[CI]:19.9%–56.1%),the median duration of CR+CRh was 19.7 months(95%CI:2.9 months–not reached[NR]),and median duration of response(DoR)was 14.3 months(95%CI:6.4 months–NR).Consistent clinical benefits and safety of ivosidenib were consistently observed at the final data cutoff with median follow-up time 26.0 months,as compared with primary data cutoff,and the data from Chinese R/R mIDH1 AML patients were also consistent with results from pivotal study.展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.42230405,42006029)Science and Technology Plan of Liaoning Province(2024JH2/102400061)+1 种基金Dalian Science and Technology Innovation Fund(2024JJ11PT007)Dalian Science and Technology Pro-gram for Innovation Talents of Dalian(2022RJ06).
文摘Mesoscale eddies play a central role in the poleward oceanic heat flux in the Southern Ocean.Previous studies have documented changes in the location of temperature fronts in the Southern Ocean,but little attention has been paid to changes in the genesis locations of mesoscale eddies.Here,we provide evidence from three decades of satellite altimetry observations for the heterogeneity of the poleward shift of mesoscale activities,with the largest trend of~0.23°±0.05°(10 yr)^(-1) over the Atlantic sector and a moderate trend of~0.1°±0.03°(10 yr)^(-1) over the Indian sector,but no significant trend in the Pacific sector.The poleward shift of mesoscale eddies is associated with a southward shift of the local westerly winds while being constrained by the major topographies.As the poleward shift of westerly winds is projected to persist,the poleward oceanic heat flux from mesoscale eddies may influence future ice melt.
文摘Ivosidenib,an isocitrate dehydrogenase 1(IDH1)inhibitor,has demonstrated clinical benefits in a pivotal study(AG120-C-001)in patients with IDH1-mutated(mIDH1)acute myeloid leukemia(AML).A registry study(CS3010-101:NCT04176393)was conducted to assess the pharmacokinetic(PK)characteristics,safety,and efficacy of ivosidenib in Chinese patients with relapsed or refractory(R/R)mIDH1 AML.Patients received ivosidenib 500 mg once daily for 28-day cycles until disease progression.Ten subjects underwent intensive PK/progressive disease(PD)assessments.All subjects had the clinical response assessed at screening,every 28 days through month 12,and then every 56 days.Between November 12,2019,and April 2,2021,30 patients were enrolled;26(86.7%)had de novo AML and 18(60.0%)were transfusion-dependent at baseline.Following single and repeated doses of ivosidenib,median time to maximum plasma concentration(T_(max))was 4.0 and 2.0 hours,respectively.The inter-individual variability of pharmacokinetic exposure was moderate to high(coefficient of variation[CV],25%–53%).No obvious accumulation was observed after repeated doses at cycle 2 day 1.Regarding the clinical response,the CR+CRh rate was 36.7%(95%confidence interval[CI]:19.9%–56.1%),the median duration of CR+CRh was 19.7 months(95%CI:2.9 months–not reached[NR]),and median duration of response(DoR)was 14.3 months(95%CI:6.4 months–NR).Consistent clinical benefits and safety of ivosidenib were consistently observed at the final data cutoff with median follow-up time 26.0 months,as compared with primary data cutoff,and the data from Chinese R/R mIDH1 AML patients were also consistent with results from pivotal study.
