Functional polymorphism in ABCA1 influences age of symptom onset in coronary artery disease patients

ATP-binding-cassette-transporter-A1 (ABCA1) plays a pivotal role in intracellular cholesterol removal, exerting a protective effect against atherosclerosis. ABCA1 gene severe mutations underlie Tangier disease, a rare Mendelian disorder that can lead to premature coronary artery disease (CAD), with age of CAD onset being two decades earlier in mutant homozygotes and one decade earlier in heterozygotes than in mutation non-carriers. It is unknown whether common polymorphisms in ABCA1 could influence age of symptom onset of CAD in the general population. We examined common promoter and non-synonymous coding polymorphisms in relation to age of symptom onset in a group of CAD patients (n = 1164), and also carried out in vitro assays to test effects of the promoter variations on ABCA1 promoter transcriptional activity and effects of the coding variations on ABCA1 function in mediating cellular cholesterol efflux. Age of symptom onset was found to be associated with the promoter - 407G > C polymorphism, being 2.82 years higher in C allele homozygotes than in G allele homozygotes and intermediate in heterozygotes (61.54, 59.79 and 58.72 years, respectively; P = 0.002). In agreement, patients carrying ABCA1 haplotypes containing the -407C allele had higher age of symptom onset. Patients of the G/G or G/C genotype of the -407G > C polymorphism had significant coronary artery stenosis (>75%) at a younger age than those of the C/C genotype (P = 0.003). Reporter gene assays showed that ABCA1 haplotypes bearing the -407C allele had higher promoter activity than haplotypes with the -407G allele. Functional analyses of the coding polymorphisms showed an effect of the V825I substitution on ABCA1 function, with the 825I variant having higher activity in mediating cholesterol efflux than the wild-type (825V). A trend towards higher symptom onset age in 825I allele carriers was observed. The data indicate an influence of common ABCA1 functional polymorphisms on age of symptom onset in CAD patients.

Association of urethral toxicity with dose exposure in combined high-dose-rate brachytherapy and intensity-modulated radiation therapy in intermediate- and high-risk prostate cancer

INTRODUCTION: To report acute and late toxicities in patients with intermediate- and high-risk prostate cancer treated with combined high-dose-rate brachytherapy (HDR-B) and intensity-modulated radiation therapy (IMRT). MATERIALS AND METHODS: From March 2003 to September 2005, 64 men were treated with a single implant HDR-B with 21 Gy given in three fractions, followed by 50 Gy IMRT along with organ tracking. Median age was 66.1 years, and risk of recurrence was intermediate in 47% of the patients or high in 53% of the patients. Androgen deprivation therapy was received by 69% of the patients. Toxicity was scored according to the CTCAE version 3.0. Median follow-up was 3.1 years. RESULTS: Acute grade 3 genitourinary (GU) toxicity was observed in 7.8% of the patients, and late grades 3 and 4 GU toxicity was observed in 10.9% and 1.6% of the patients. Acute grade 3 gastrointestinal (GI) toxicity was experienced by 1.6% of the patients, and late grade 3 GI toxicity was absent. The urethral V(120) (urethral volume receiving > or =120% of the prescribed HDR-B dose) was associated with acute (P=.047) and late > or = grade 2 GU toxicities (P=.049). CONCLUSIONS: Late grades 3 and 4GU toxicity occurred in 10.9% and 1.6% of the patients after HDR-B followed by IMRT in association with the irradiated urethral volume. The impact of V(120) on GU toxicity should be validated in further studies.

Toxicity and early treatment outcomes in low- and intermediate-risk prostate cancer managed by high-dose-rate brachytherapy as a monotherapy

PURPOSE: To determine the acute and late genitourinary (GU) and gastrointestinal (GI) toxicity and present short-term biochemical no evidence of disease (bNED) rates after high-dose-rate brachytherapy (HDR-B) monotherapy. METHODS AND MATERIALS: Between October 2003 and June 2006, 36 patients with low (28) and intermediate (8) risk prostate cancer (PCA) were treated by HDR-B monotherapy. All patients received one implant and four fractions of 9.5Gy within 48h for a total prescribed dose (PD) of 38Gy. Five patients received hormonal therapy (HT). Median age was 63.5 years and median followup was 3 years (range, 0.4-4 years). Toxicity was scored according to the CTCAE version 3.0. Biochemical failure was defined according to the Phoenix criteria. RESULTS: Acute and late Grade 3 GU toxicity was observed in 1 (3%) and 4 (11%) patients, respectively. Grade 3 GI toxicity was absent. The three- year bNED survival rate was 100%. The sexual preservation rate in patients without HT was 75%. Late Grade 3 GU toxicity was associated with the planning target volume (PTV) V(100) (% PTV receiving > or =100% of the PD; p=0.036), D(90) (dose delivered to 90% of the PTV; p=0.02), and the urethral V(120) (urethral volume receiving > or =120% of the PD; p=0.043). The urethral V(120) was associated with increased PTV V(100) (p<0.001) and D(90) (p=0.003). CONCLUSIONS: After HDR-B monotherapy, late Grade 3 GU toxicity is associated with the urethral V(120) and the V(100) and D(90) of the PTV. Decrease of the irradiated urethral volume may reduce the GU toxicity and potentially improve the therapeutic ratio of this treatment.

Prospective population-based study of RSV-related intermediate care and intensive care unit admissions in Switzerland over a 4-year period (2001-2005)

OBJECTIVES: Respiratory syncytial virus (RSV) infections are a leading cause of hospital admissions in small children. A substantial proportion of these patients require medical and nursing care, which can only be provided in intermediate (IMC) or intensive care units (ICU). This article reports on all children aged < 3 years who required admission to IMC and/or ICU between October 1, 2001 and September 30, 2005 in Switzerland. PATIENTS AND METHODS: We prospectively collected data on all children aged < 3 years who were admitted to an IMC or ICU for an RSV-related illness. Using a detailed questionnaire, we collected information on risk factors, therapy requirements, length of stay in the IMC/ICU and hospital, and outcome. RESULTS: Of the 577 cases reported during the study period, 90 were excluded because the patients did not fulfill the inclusion criteria; data were incomplete in another 25 cases (5%). Therefore, a total of 462 verified cases were eligible for analysis. At the time of hospital admission, only 31 patients (11%) were older than 12 months. Since RSV infection was not the main reason for IMC/ICU admission in 52% of these patients, we chose to exclude this subgroup from further analyses. Among the 431 infants aged < 12 months, the majority (77%) were former near term or full term (NT/FT) infants with a gestational age > or = 35 weeks without additional risk factors who were hospitalized at a median age of 1.5 months. Gestational age (GA) < 32 weeks, moderate to severe bronchopulmonary dysplasia (BPD), and congenital heart disease (CHD) were all associated with a significant risk increase for IMC/ICU admission (relative risk 14, 56, and 10, for GA < or = 32 weeks, BPD, and CHD, respectively). Compared with NT/FT infants, high-risk infants were hospitalized at an older age (except for infants with CHD), required more invasive and longer respiratory support, and had longer stays in the IMC/ICU and hospital. CONCLUSIONS: In Switzerland, RSV infections lead to the IMC/ICU admission of approximately 1%-2% of each annual birth cohort. Although prematurity, BPD, and CHD are significant risk factors, non-pharmacological preventive strategies should not be restricted to these high-risk patients but also target young NT/FT infants since they constitute 77% of infants requiring IMC/ICU admission.

OSL and TL dating of the Middle Stone Age sequence at Diepkloof Rock Shelter (South Africa): a clarification

Diepkloof Rock Shelter offers an exceptional opportunity to study the onset and evolution of both Still Bay (SB) and Howiesons Poort (HP) techno-complexes. However, previous age estimates based on luminescence dating of burnt quartzites (Tribolo et al., 2009) and of sediments (Jacobs et al., 2008) were not in agreement. Here, we present new luminescence ages for 17 rock samples (equivalent dose estimated with a SAR-ITL protocol instead of classical MAAD-TL) as well as for 5 sediment samples (equivalent dose estimated with SAR-single grain OSL protocol) and an update of the 22 previous age estimates for burnt lithics (modified calibration and beta dose estimates). While a good agreement between the rock and sediment ages is obtained, these estimates are still significantly older than those reported by Jacobs et al. (2008). After our own analyses of the sediment from Diepkloof, it is suspected that these authors did not correctly chose the parameters for the equivalent dose determination, leading to an underestimate of the equivalent doses, and thus of the ages. From bottom to top, the mean ages are 100 ± 10 ka for stratigraphic unit (SU) Noël and 107 ± 11 ka for SU Mark (uncharacterized Lower MSA), 100 ± 10 ka for SU Lynn-Leo (Pre-SB type Lynn), 109 ± 10 ka for SUs Kim-Larry (SB), 105 ± 10 ka for SUs Kerry-Kate and 109 ± 10 ka for SU Jess (Early HP), 89 ± 8 ka for SU Jude (MSA type Jack), 77 ± 8 ka for SU John, 85 ± 9 ka for SU Fox, 83 ± 8 ka for SU Fred and 65 ± 8 ka for SU OB5 (Intermediate HP), 52 ± 5 ka for SUs OB2-4 (Late HP). This chronology, together with the technological analyses, greatly modifies the current chrono-cultural model regarding the SB and the HP and has important archaeological implications. Indeed, SB and HP no longer appear as short-lived techno-complexes with synchronous appearances for each and restricted to Oxygen Isotopic Stage (OIS) 4 across South Africa, as suggested by Jacobs et al. (2008, 2012). Rather, the sequence of Diepkloof supports a long chronology model with an early appearance of both SB and HP in the first half of OIS 5 and a long duration of the HP into OIS 3. These new dates imply that different technological traditions coexisted during OIS 5 and 4 in southern Africa and that SB and HP can no longer be considered as horizon markers.

Historical and idealized climate model experiments: an intercomparison of Earth system models of intermediate complexity

Both historical and idealized climate model experiments are performed with a variety of Earth system models of intermediate complexity (EMICs) as part of a community contribution to the Intergovernmental Panel on Climate Change Fifth Assessment Report. Historical simulations start at 850 CE and continue through to 2005. The standard simulations include changes in forcing from solar luminosity, Earth's orbital configuration, CO2, additional greenhouse gases, land use, and sulphate and volcanic aerosols. In spite of very different modelled pre-industrial global surface air temperatures, overall 20th century trends in surface air temperature and carbon uptake are reasonably well simulated when compared to observed trends. Land carbon fluxes show much more variation between models than ocean carbon fluxes, and recent land fluxes appear to be slightly underestimated. It is possible that recent modelled climate trends or climate–carbon feedbacks are overestimated resulting in too much land carbon loss or that carbon uptake due to CO2 and/or nitrogen fertilization is underestimated. Several one thousand year long, idealized, 2 × and 4 × CO2 experiments are used to quantify standard model characteristics, including transient and equilibrium climate sensitivities, and climate–carbon feedbacks. The values from EMICs generally fall within the range given by general circulation models. Seven additional historical simulations, each including a single specified forcing, are used to assess the contributions of different climate forcings to the overall climate and carbon cycle response. The response of surface air temperature is the linear sum of the individual forcings, while the carbon cycle response shows a non-linear interaction between land-use change and CO2 forcings for some models. Finally, the preindustrial portions of the last millennium simulations are used to assess historical model carbon-climate feedbacks. Given the specified forcing, there is a tendency for the EMICs to underestimate the drop in surface air temperature and CO2 between the Medieval Climate Anomaly and the Little Ice Age estimated from palaeoclimate reconstructions. This in turn could be a result of unforced variability within the climate system, uncertainty in the reconstructions of temperature and CO2, errors in the reconstructions of forcing used to drive the models, or the incomplete representation of certain processes within the models. Given the forcing datasets used in this study, the models calculate significant land-use emissions over the pre-industrial period. This implies that land-use emissions might need to be taken into account, when making estimates of climate–carbon feedbacks from palaeoclimate reconstructions.

Age models and stable isotope ratios from the Mid-Miocene

Mid-Miocene pelagic sedimentary sections can be correlated using intermediate and high resolution oxygen and carbon isotopic records of benthic foraminifera. Precision of a few tens of thousands of years is readily achievable at sites with high sedimentation rates, for example, Deep Sea Drilling Project sites 289 and 574. The mid-Miocene carbon isotope records are characterized by an interval of high d13C values between 17 and 13.5 Ma (the Monterey Excursion of Vincent and Berger 1985) upon which are superimposed a series of periodic or quasi-periodic fluctuations in d13C values. These fluctuations have a period of approximately 440 kyr, suggestive of the 413 kyr cycle predicted by Milankovitch theory. Vincent and Berger proposed that the Monterey Excursion was the result of increased organic carbon burial in continental margins sediments. The increased d13C values (called 13C maxima) superimposed on the generally high mid-Miocene signal coincide with increases in d18O values suggesting that periods of cooling and/or ice buildup were associated with exceptionally rapid burial of organic carbon and lowered atmospheric CO2 levels. It is likely that during the Monterey Excursion the ocean/atmosphere system became progressively more sensitive to small changes in insolation, ultimately leading to major cooling of deep water and expansion of continental ice. We have assigned an absolute chronology, based on biostratigraphic and magneto-biostratigraphic datum levels, to the isotope stratigraphy and have used that chronology to correlate unconformities, seismic reflectors, carbonate minima, and dissolution intervals. Intervals of sediment containing 13C maxima are usually better preserved than the overlying and underlying sediments, indicating that the d13C values of TCO2 in deep water and the corrosiveness of seawater are inversely correlated. This again suggests that the 13C maxima were associated with rapid burial of organic carbon and reduced levels of atmospheric CO2. The absolute chronology we have assigned to the isotopic record indicates that the major mid-Miocene deepwater cooling/ice volume expansion took 2 m.y. and was not abrupt as had been reported previously. The cooling appears abrupt at many sites because the interval is characterized by a number of dissolution intervals. The cooling was not monotonic, and the 2 m.y. interval included an episode of especially rapid cooling as well as a brief return to warmer conditions before the final phase of the cooling period. The increase in d18O values of benthic foraminifera between 14.9 and 12.9 Ma was greatest at deeper water sites and at sites closest to Antarctica. The data suggest that the d18O value of seawater increased by no more than about 1.1 per mil during this interval and that the remainder of the change in benthic d18O values resulted from cooling in Antarctic regions of deepwater formation. Equatorial planktonic foraminifera from sites 237 and 289 exhibit a series of 0.4 per mil steplike increases in d13C values. Only one of these increases in planktonic d13C is correlated with any of the features in the mid-Miocene benthic carbon isotope record.

Age and chemical composition of apatites from five DSDP and ODP Sites in the Pacific, Atlantic and Indian Oceans

Since studies on deep-sea cores were carried out in the early 1990s it has been known that ambient temperature may have a marked affect on apatite fission track annealing. Due to sluggish annealing kinetics, this effect cannot be quantified by laboratory annealing experiments. The unknown amount of low-temperature annealing remains one of the main uncertainties for extracting thermal histories from fission track data, particularly for samples which experienced slow cooling in shallow crustal levels. To further elucidate these uncertainties, we studied volcanogenic sediments from five deep-sea drill cores, that were exposed to maximum temperatures between ~10° and 70°C over geological time scales of ~15-120 Ma. Mean track lengths (MTL) and etch pit diameters (Dpar) of all samples were measured, and the chemical composition of each grain analyzed for age and track length measurements was determined by electron microprobe analysis. Thermal histories of the sampled sites were independently reconstructed, based on vitrinite reflectance measurements and/or 1D numerical modelling. These reconstructions were used to test the most widely used annealing models for their ability to predict low-temperature annealing. Our results show that long-term exposure to temperatures below the temperature range of the nominal apatite fission track partial annealing zone results in track shortening ranging between 4 and 11%. Both chlorine content and Dpar values explain the downhole annealing patterns equally well. Low chlorine apatite from one drill core revealed a systematic relation between Si-content and Dpar value. The question whether Si-substitution in apatite has direct and systematic effects on annealing properties however, cannot be addressed by our data. For samples, which remained at temperatures <30°C, and which are low in chlorine, the Laslett et al. [Laslett G., Green P., Duddy I. and Gleadow A. (1987) Thermal annealing of fission tracks in apatite. Chem. Geol. 65, 1-13] annealing model predicts MTL up to 0.6 µm longer than those actually measured, whereas for apatites with intermediate to high chlorine content, which experienced temperatures >30°C, the predictions of the Laslett et al. (1987) model agree with the measured MTL data within error levels. With few exceptions, predictions by the Ketcham et al. [Ketcham R., Donelick R. and Carlson W. (1999) Variability of apatite fission-track annealing kinetics. III: Extrapolation to geological time scales. Am. Mineral. 84/9, 1235-1255] annealing model are consistent with the measured data for samples which remained at temperatures below ~30°C. For samples which experienced maximum temperatures between ~30 and 70°C, and which are rich in chlorine, the Ketcham et al. (1999) model overestimates track annealing.

Age determination of sediment cores close to the Strait of Gibralta

A suit of sediment cores close to and south of the Strait of Gibraltar (12°-36°N, 500-2800 m water depth) were analyzed for stable isotopes in epibenthic foraminifers Cibicidoides wuellerstorfi and Planulina ariminensis. During peak glacial times, the data exhibit higher delta13C values of up to 1.6 per mil at intermediate depths near the Strait of Gibraltar (36°N). The values decrease to the south as evidenced by our data, but also to the north as revealed by data of intermediate depth cores north of 38°N (in Duplessy et al. (1987)). Thus, the distribution pattern of delta13C provides crucial evidence for an increased influence of nutrient depleted Mediterranean Outflow Water (MOW) on the glacial northeast Atlantic hydrography. During oxygen isotope Terminations I and II, the meridional carbon isotope gradient indicates a significantly decreased but still active MOW. As deduced from the delta18O fluctuations, the temperatures of the MOW in the Atlantic were lower during glacial times by as much as 5°C. During glacial times and during Termination I the maximum delta13C values of the MOW correlate with minimum values of the North Atlantic Deep Water (NADW) and vice versa. This inverse response to climatic change of the carbon isotope signals of both water masses indicates, that the supply of saline MOW to the north Atlantic may be less important for the formation of NADW than previously assumed.

Age determination and geochemistry of corals from the North Pacific

A depth transect of deep-sea bamboo corals along the California margin provides evidence that coral strontium to calcium ratios (Sr/Ca[coral]) record seawater Sr/Ca ratios (Sr/Ca[sw]). A calibration was constructed utilizing Sr/Ca[coral] ratios and previously published Pacific Sr/Ca[sw] data (R**2 = 0.53, n = 12, p < 0.01): Sr/Ca[coral] (mmol/mol) = 4.62*Sr/Ca[sw] (mmol/mol) - 36.64. Sr/Ca[sw] is ultimately governed by the remineralization of Sr-containing shells of surface water-derived marine organisms (e.g., Acantharia) at intermediate water depths. California margin Sr/Cacoral records from 792 and 1295 m document fluctuations in Sr/Ca[sw] that appear decadal-scale. These results suggest that Sr/Casw may not be as stable as previously assumed and may be influenced by surface productivity on short timescales.

Age models of five ice cores from the Dronning Maud Land, Antarctica

For the first time, annually resolved accumulation rates have been determined in central Antarctica by means of counting seasonal signals of ammonium, calcium, and sodium. All records, obtained from three intermediate depth ice cores from Dronning Maud Land, East Antarctica, show rather constant accumulation rates throughout the last 9 centuries with mean values of 63, 61, and 44 mm H2O yr**-1 and a typical year-to-year variation of about 30%. For the last few decades, no trend was detected accounting for the high natural variability of all records. A significant weak intersite correlation is apparent only between two cores when the high-frequency part with periods less than 30 years is removed. By analyzing the records in the frequency domain, no persistent periods were found. This suggests that the snow accumulation in this area is mainly influenced by local deposition patterns and may be additionally masked by redistribution of snow due to wind. By comparing accumulation rates over the last 2 millennia a distinct change in the layer thickness in one of the three cores was found, which might be attributed either to an area upstream of the drilling site with lower accumulation rates, or to deposition processes influenced by surface undulations. The missing of a clear correlation between the accumulation rate histories at the three locations is also important for the interpretation of small, short time variations of past precipitation records obtained from deep ice cores.

Gotland Deep (Baltic Sea) independent age model based on Palaeomagnetic Secular Variation (PSV) and lead (Pb) deposition profiles

Dating of sediment cores from the Baltic Sea has proven to be difficult due to uncertainties surrounding the 14C reservoir age and a scarcity of macrofossils suitable for dating. Here we present the results of multiple dating methods carried out on cores in the Gotland Deep area of the Baltic Sea. Particular emphasis is placed on the Littorina stage (8 ka ago to the present) of the Baltic Sea and possible changes in the 14C reservoir age of our dated samples. Three geochronological methods are used. Firstly, palaeomagnetic secular variations (PSV) are reconstructed, whereby ages are transferred to PSV features through comparison with varved lake sediment based PSV records. Secondly, lead (Pb) content and stable isotope analysis are used to identify past peaks in anthropogenic atmospheric Pb pollution. Lastly, 14C determinations were carried out on benthic foraminifera (Elphidium spec.) samples from the brackish Littorina stage of the Baltic Sea. Determinations carried out on smaller samples (as low as 4 µg C) employed an experimental, state-of-the-art method involving the direct measurement of CO2 from samples by a gas ion source without the need for a graphitisation step - the first time this method has been performed on foraminifera in an applied study. The PSV chronology, based on the uppermost Littorina stage sediments, produced ten age constraints between 6.29 and 1.29 cal ka BP, and the Pb depositional analysis produced two age constraints associated with the Medieval pollution peak. Analysis of PSV data shows that adequate directional data can be derived from both the present Littorina saline phase muds and Baltic Ice Lake stage varved glacial sediments. Ferrimagnetic iron sulphides, most likely authigenic greigite (Fe3S4), present in the intermediate Ancylus Lake freshwater stage sediments acquire a gyroremanent magnetisation during static alternating field (AF) demagnetisation, preventing the identification of a primary natural remanent magnetisation for these sediments. An inferred marine reservoir age offset (deltaR) is calculated by comparing the foraminifera 14C determinations to a PSV & Pb age model. This deltaR is found to trend towards younger values upwards in the core, possibly due to a gradual change in hydrographic conditions brought about by a reduction in marine water exchange from the open sea due to continued isostatic rebound.

Composition and age of volcanic rocks from the Sinii Utes Depression, Southern Primoye

New data are reported on structure of sections, chemical composition, and age of volcano-sedimentary and volcanic rocks from the Sinii Utes Depression in the Southern Primorye region. The Sinii Utes Depression is filled with two sequences: the lower sequence composed of sedimentary-volcanogenic coaliferous rocks (the stratotype of the Sinii Utes Formation) and the upper sequence consisting of tephroid with overlying basalts. This work considers chemical composition and problems of K-Ar dating of basalts. The uppermost basaltic flow has K-Ar age 22.0±1.0 Ma. The dates obtained for the middle and upper parts of lava flows are underestimated. It is explained by their heating due to combustion of brown coals of the Sinii Utes Formation underlying the lava flow. Calculations show that argon could only partly have been removed from the basalts owing to conductive heat transfer and was lost largely due to infiltration of hot gases in heterogeneous fissured medium. Basaltic volcanism on continental margins of the southern Primorye region and the adjacent Korean and Chinese areas at the Oligocene-Miocene boundary preceded Early-Middle Miocene spreading and formation of the Sea of Japan basin. Undifferentiated moderately alkaline basalts of intraplate affinity developed in the Amba Depression and some other structures of the southern Primorye region and intraplate alkali basalts of the Phohang Graben in the Korean Peninsula serve as indicators of incipient spreading regime in the Sea of Japan. Potassic basalt-trachybasalt eruptions occurred locally in riftogenic depressions and shield volcanoes. In some structures this volcanism was terminated by eruptions of intermediate and acid lavas. Such evolution of volcanism is explained by selective contamination of basaltic melts during their interaction with crustal acid material and generation of acid anatectic melts.

(Table 1) Sea-surface temperatures, intermediate-water temperatures, and latitudinal gradient at three time slices at the end of the Cretaceous

Climatic and oceanographic variations during the last 2 m.y. of the Maastrichtian inferred from high-resolution (10 k.y.) stable isotope analysis of the mid-latitude South Atlantic Deep Sea Drilling Project Site 525 reveal a major warm pulse followed by rapid cooling prior to the Cretaceous-Tertiary boundary. Between 66.85 and 65.52 Ma, cool but fluctuating temperatures average 9.9 and 15.4°C in intermediate and surface waters, respectively. This interval is followed by an abrupt short-term warming between 65.45 and 65.11 Ma, which increased temperatures by 2-3°C in intermediate waters, and decreased the vertical thermal gradient to an average of 2.7°C. This warm pulse may be linked to increased atmospheric pCO2, increased poleward heat transport, and the switch of an intermediate water source from high to low-middle latitudes. During the last 100 k.y. of the Maastrichtian, intermediate and surface temperatures decreased by an average of 2.1 and 1.4°C, respectively, compared to the maximum temperature between 65.32 and 65.24 Ma.