History of oceanic front development in the New Zealand sector of the Southern Ocean during the Cenozoic--a synthesis

The New Zealand sector of the Southern Ocean (NZSSO) has opened about the Indian-Pacific spreading ridge throughout the Cenozoic. Today the NZSSO is characterised by broad zonal belts of antarctic (cold), subantarctic (cool), and subtropical (warm) surface-water masses separated by prominent oceanic fronts: the Subtropical Front (STF) c. 43deg.S, Subantarctic Front (SAF) c. 50deg.S, and Antarctic Polar Front (AAPF) c. 60deg.S. Despite a meagre database, the broad pattern of Cenozoic evolution of these fronts is reviewed from the results of Deep Sea Drilling Project-based studies of sediment facies, microfossil assemblages and diversity, and stable isotope records, as well as from evidence in onland New Zealand Cenozoic sequences. Results are depicted schematically on seven paleogeographic maps covering the NZSSO at 10 m.y. intervals through the Cenozoic. During the Paleocene and most of the Eocene (65-35 Ma), the entire NZSSO was under the influence of warm to cool subtropical waters, with no detectable oceanic fronts. In the latest Eocene (c. 35 Ma), a proto-STF is shown separating subantarctic and subtropical waters offshore from Antarctica, near 65deg.S paleolatitude. During the earliest Oligocene, this front was displaced northwards by development of an AAPF following major global cooling and biotic turnover associated with ice sheet expansion to sea level on East Antarctica. Early Oligocene full opening (c. 31 Ma) of the Tasmanian gateway initiated vigorous proto-circum-Antarctic flow of cold/cool waters, possibly through a West Antarctic seaway linking the southern Pacific and Atlantic Oceans, including detached northwards "jetting" onto the New Zealand plateau where condensation and unconformity development was widespread in cool-water carbonate facies. Since this time, a broad tripartite division of antarctic, subantarctic, and subtropical waters has existed in the NZSSO, including possible development of a proto-SAF within the subantarctic belt. In the Early-early Middle Miocene (25-15 Ma), warm subtropical waters expanded southwards into the northern NZSSO, possibly associated with reduced ice volume on East Antarctica but particularly with restriction of the Indonesian gateway and redirection of intensified warm surface flows southwards into the Tasman Sea, as well as complete opening of the Drake gateway by 23 Ma allowing more complete decoupling of cool circum-Antarctic flow from the subtropical waters. During the late Middle-Late Miocene (15-5 Ma), both the STF and SAF proper were established in their present relative positions across and about the Campbell Plateau, respectively, accompanying renewed ice buildup on East Antarctica and formation of a permanent ice sheet on West Antarctica, as well as generally more expansive and intensified circum-Antarctic flow. The ultimate control on the history of oceanic front development in the NZSSO has been plate tectonics through its influence on the paleogeographic changes of the Australian-New Zealand-Antarctic continents and their intervening oceanic basins, the timing of opening and closing of critical seaways, the potential for submarine ridges and plateaus to exert some bathymetric control on the location of fronts, and the evolving ice budget on the Antarctic continent. The broad trends of the Cenozoic climate curve for New Zealand deduced from fossil evidence in the uplifted marine sedimentary record correspond well to the principal paleoceanographic events controlling the evolution and migration of the oceanic fronts in the NZSSO

Molecular response and quality of life in chronic myeloid leukemia patients treated with intermittent TKIs: First interim analysis of OPTkIMA study

31noBackground: Intermittent treatment with TKIs is an option for the great majority (70%–80%) of CML patients who do not achieve a stable deep molecular response and are not eligible for treatment discontinuation. For these patients, the only alternative is to assume TKI continuously, lifelong. Methods: The Italian phase III multicentric randomized OPTkIMA study started in 2015, with the aim to evaluate if a progressive de-escalation of TKIs (imatinib, nilotinib, and dasatinib) is able to maintain the molecular response (MR3.0) and to improve Health Related Quality of Life (HRQoL). Results: Up to December 2018, 166/185 (90%) elderly CML patients in stable MR3.0/MR4.0 completed the first year of any TKI intermittent schedule 1 month ON and 1 month OFF. The first year probability of maintaining the MR3.0 was 81% and 23.5% of the patients who lost the molecular response regained the MR3.0 after resuming TKI continuously. Patients’ HRQoL at baseline was better than that of matched peers from healthy population. Women was the only factor independently associated with worse baseline HRQoL (p > 0.0001). Overall, global HRQoL worsened at 6 (p < 0.001) but returned to the baseline value at 12 months and it was statistically significantly worse in women (p = 0.001). Conclusions: De-escalation of any TKI by 1 month ON/OFF schedule maintains the MR3.0/MR4.0 in 81% of the patients during the first 12–24 months. No patients progressed to accelerated/blastic phase, all the patients (23.5%) losing MR3.0 regained the MR3.0 and none suffered from TKI withdrawn syndrome. The study firstly report on HRQoL in elderly CML patients moving from a continuous daily therapy to a de-escalated intermittent treatment.openopenMalagola M.; Iurlo A.; Abruzzese E.; Bonifacio M.; Stagno F.; Binotto G.; D'Adda M.; Lunghi M.; Crugnola M.; Ferrari M.L.; Lunghi F.; Castagnetti F.; Rosti G.; Lemoli R.M.; Sancetta R.; Coppi M.R.; Corsetti M.T.; Rege Cambrin G.; Romano A.; Tiribelli M.; Russo Rossi A.; Russo S.; Aprile L.; Gandolfi L.; Farina M.; Bernardi S.; Polverelli N.; Roccaro A.M.; De Vivo A.; Baccarani M.; Russo D.Malagola, M.; Iurlo, A.; Abruzzese, E.; Bonifacio, M.; Stagno, F.; Binotto, G.; D'Adda, M.; Lunghi, M.; Crugnola, M.; Ferrari, M. L.; Lunghi, F.; Castagnetti, F.; Rosti, G.; Lemoli, R. M.; Sancetta, R.; Coppi, M. R.; Corsetti, M. T.; Rege Cambrin, G.; Romano, A.; Tiribelli, M.; Russo Rossi, A.; Russo, S.; Aprile, L.; Gandolfi, L.; Farina, M.; Bernardi, S.; Polverelli, N.; Roccaro, A. M.; De Vivo, A.; Baccarani, M.; Russo, D

Determinants of frontline tyrosine kinase inhibitor choice for patients with chronic-phase chronic myeloid leukemia: A study from the Registro Italiano LMC and Campus CML

BackgroundImatinib, dasatinib, and nilotinib are tyrosine kinase inhibitors (TKIs) approved in Italy for frontline treatment of chronic-phase chronic myeloid leukemia (CP-CML). The choice of TKI is based on a combined evaluation of the patient's and the disease characteristics. The aim of this study was to analyze the use of frontline TKI therapy in an unselected cohort of Italian patients with CP-CML to correlate the choice with the patient's features. MethodsA total of 1967 patients with CP-CML diagnosed between 2012 and 2019 at 36 centers throughout Italy were retrospectively evaluated; 1089 patients (55.4%) received imatinib and 878 patients (44.6%) received a second-generation (2G) TKI. ResultsSecond-generation TKIs were chosen for most patients aged &lt;45 years (69.2%), whereas imatinib was used in 76.7% of patients aged &gt;65 years (p &lt; .001). There was a predominant use of imatinib in intermediate/high European long-term survival risk patients (60.0%/66.0% vs. 49.7% in low-risk patients) and a limited use of 2G-TKIs in patients with comorbidities such as hypertension, diabetes, chronic obstructive pulmonary disease, previous neoplasms, ischemic heart disease, or stroke and in those with &gt;3 concomitant drugs. We observed a greater use of imatinib (61.1%) in patients diagnosed in 2018-2019 compared to 2012-2017 (53.2%; p = .002). In multivariable analysis, factors correlated with imatinib use were age &gt; 65 years, spleen size, the presence of comorbidities, and &amp; GE;3 concomitant medications. ConclusionsThis observational study of almost 2000 cases of CML shows that imatinib is the frontline drug of choice in 55% of Italian patients with CP-CML, with 2G-TKIs prevalently used in younger patients and in those with no concomitant clinical conditions. Introduction of the generic formulation in 2018 seems to have fostered imatinib use

Managing chronic myeloid leukemia for treatment-free remission: A proposal from the GIMEMA CML WP

Several papers authored by international experts have proposed recommendations on the management of BCR-ABL11 chronic myeloid leukemia (CML). Following these recommendations, survival of CML patients has become very close to normal. The next, ambitious, step is to bring as many patients as possible into a condition of treatment-free remission (TFR). The Gruppo Italiano Malattie EMatologiche dell'Adulto (GIMEMA; Italian Group for Hematologic Diseases of the Adult) CML Working Party (WP) has developed a project aimed at selecting the treatment policies that may increase the probability of TFR, taking into account 4 variables: the need for TFR, the tyrosine kinase inhibitors (TKIs), the characteristics of leukemia, and the patient. A Delphi-like method was used to reach a consensus among the representatives of 50 centers of the CML WP. A consensus was reached on the assessment of disease risk (EUTOS Long Term Survival [ELTS] score), on the definition of the most appropriate age boundaries for the choice of first-line treatment, on the choice of the TKI for first-line treatment, and on the definition of the responses that do not require a change of the TKI (BCR-ABL1 ≤10% at 3 months, ≤1% at 6 months, ≤0.1% at 12 months, ≤0.01% at 24 months), and of the responses that require a change of the TKI, when the goal is TFR (BCR-ABL1 &gt;10% at 3 and 6 months, &gt;1% at 12 months, and &gt;0.1% at 24 months). These suggestions may help optimize the treatment strategy for TFR

Late pleistocene sedimentation history of the Shirshov Ridge, Bering Sea

The analysis of the lithology, grain-size distribution, clay minerals, and geochemistry of Upper Pleistocene sediments from the submarine Shirshov Ridge (Bering Sea) showed that the main source area was the Yukon–Tanana terrane of Central Alaska. The sedimentary materials were transported by the Yukon River through Beringia up to the shelf break, where they were entrained by a strong northwestward-flowing sea current. The lithological data revealed several pulses of ice-rafted debris deposition, roughly synchronous with Heinrich events, and periods of weaker bottom-current intensity. Based on the geochemical results, we distinguished intervals of an increase in paleoproductivity and extension of the oxygen minimum zone. The results suggest that there were three stages of deposition driven by glacioeustatic sea-level fluctuations and glacial cycles in Alaska

Evidence from diatom-bound nitrogen isotopes for subarctic Pacific stratification during the last ice age and a link to North Pacific denitrification changes

Author Posting. © American Geophysical Union, 2007. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Paleoceanography 22 (2007): PA1215, doi:10.1029/2005PA001205.In a piston core from the central Bering Sea, diatom microfossil-bound N isotopes and the concentrations of opal, biogenic barium, calcium carbonate, and organic N are measured over the last glacial/interglacial cycle. Compared to the interglacial sections of the core, the sediments of the last ice age are characterized by 3‰ higher diatom-bound δ 15N, 70 wt % lower opal content and 1200 ppm lower biogenic barium. Taken together and with constraints on sediment accumulation rate, these results suggest a reduced supply of nitrate to the surface due to stronger stratification of the upper water column of the Bering Sea during glacial times, with more complete nitrate consumption resulting from continued iron supply through atmospheric deposition. This finding extends the body of evidence for a pervasive link between cold climates and polar ocean stratification. In addition, we hypothesize that more complete nutrient consumption in the glacial age subarctic Pacific contributed to the previously observed ice age reduction in suboxia and denitrification in the eastern tropical North Pacific by lowering the nutrient content of the intermediate-depth water formed in the subpolar North Pacific. In the deglacial interval of the Bering Sea record, two apparent peaks in export productivity are associated with maxima in diatom-bound and bulk sediment δ 15N. The high δ 15N in these intervals may have resulted from greater surface nutrient consumption during this period. However, the synchroneity of the deglacial peaks in the Bering Sea with similar bulk sediment δ 15N changes in the eastern Pacific margin and the presence of sediment lamination within the Bering Sea during the deposition of the productivity peaks raise the possibility that both regional and local denitrification worked to raise the δ 15N of the nitrate feeding Bering Sea surface waters at these times.Financial support for this work was provided by NSF grants OCE-0136449, OCE-9981479, ANT-0453680, by BP and Ford Motor Company through the Princeton Carbon Migration Initiative, and by a NDSEG fellowship to B.G.B. Work conducted aboard the USCG Healy (Healy 0202) was funded by grant OPP-9912122

Compound-specific radiocarbon dating of the varved Holocene sedimentary record of Saanich Inlet, Canada

Author Posting. © American Geophysical Union, 2004. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Paleoceanography 19 (2004): PA2012, doi:10.1029/2003PA000927.The radiocarbon contents of various biomarkers extracted from the varve-counted sediments of Saanich Inlet, Canada, were determined to assess their applicability for dating purposes. Calibrated ages obtained from the marine planktonic archaeal biomarker crenarchaeol compared favorably with varve-count ages. The same conclusion could be drawn for a more general archaeal biomarker (GDGT-0), although this biomarker proved to be less reliable due to its less-specific origin. The results also lend support to earlier indications that marine crenarchaeota use dissolved inorganic carbon (DIC) as their carbon source. The average reservoir age offset ΔR of 430 years, determined using the crenarchaeol radiocarbon ages, varied by ±110 years. This may be caused by natural variations in ocean-atmosphere mixing or upwelling at the NE Pacific coast but variability may also be due to an inconsistency in the marine calibration curve when used at sites with high reservoir ages.This work was supported by the Netherlands Organization for Scientific Research (NWO) and NSF grants OCE-9907129 and OCE-0137005 (Eglinton)