Dansgaard-Oeschger cycles of the penultimate and last glacial period recorded in stalagmites from Türkiye.

The last glacial period is characterized by abrupt climate oscillations, also known as Dansgaard-Oeschger (D-O) cycles. However, D-O cycles remain poorly documented in climate proxy records covering the penultimate glacial period. Here we present highly resolved and precisely dated speleothem time series from Sofular Cave in northern Türkiye to provide clear evidence for D-O cycles during Marine Isotope Stage (MIS) 6 as well as MIS 2-4. D-O cycles are most clearly expressed in the Sofular carbon isotope time series, which correlate inversely with regional sea surface temperature (SST) records from the Black Sea. The pacing of D-O cycles is almost twice as long during MIS 6 compared to MIS 2-4, and could be related to a weaker Atlantic Meridional Overturning Circulation (AMOC) and a different mean climate during MIS 6 compared to MIS 2-4, leading most likely to a higher threshold for the occurrence of D-O cycles.

Speleothem record of mild and wet mid-Pleistocene climate in northeast Greenland.

The five interglacials before the Mid-Brunhes Event (MBE) [c.430 thousand years (ka) ago] are generally considered to be globally cooler than those post-MBE. Inhomogeneities exist regionally, however, which suggest that the Arctic was warmer than present during Marine Isotope Stage (MIS) 15a. Using the first speleothem record for the High Arctic, we investigate the climatic response of northeast Greenland between c.588 and c.549 ka ago. Our results indicate an enhanced warmth of at least +3.5°C relative to the present, leading to permafrost thaw and increased precipitation. We find that δ18O of precipitation was at least 3‰ higher than today and recognize two local cooling events (c.571 and c.594 ka ago) thought to be caused by freshwater forcing. Our results are important for improving understanding of the regional climatic response leading up to the MBE and specifically provide insights into the climatic response of a warmer Arctic.

Evidence of thermophilisation and elevation-dependent warming during the Last Interglacial in the Italian Alps.

Thermophilisation is the response of plants communities in mountainous areas to increasing temperatures, causing an upward migration of warm-adapted (thermophilic) species and consequently, the timberline. This greening, associated with warming, causes enhanced evapotranspiration that leads to intensification of the hydrological cycle, which is recorded by hydroclimate-sensitive archives, such as stalagmites and flowstones formed in caves. Understanding how hydroclimate manifests at high altitudes is important for predicting future water resources of many regions of Europe that rely on glaciers and snow accumulation. Using proxy data from three coeval speleothems (stalagmites and flowstone) from the Italian Alps, we reconstructed both the ecosystem and hydrological setting during the Last Interglacial (LIG); a warm period that may provide an analogue to a near-future climate scenario. Our speleothem proxy data, including calcite fabrics and the stable isotopes of calcite and fluid inclusions, indicate a +4.3 ± 1.6 °C temperature anomaly at ~2000 m a.s.l. for the peak LIG, with respect to present-day values (1961-1990). This anomaly is significantly higher than any low-altitude reconstructions for the LIG in Europe, implying elevation-dependent warming during the LIG. The enhanced warming at high altitudes must be accounted for when considering future climate adaption strategies in sensitive mountainous regions.

Estimating the upper limit of prehistoric peak ground acceleration using an in situ, intact and vulnerable stalagmite from Plavecká priepast cave (Detrekoi-zsomboly), Little Carpathians, Slovakia-first results.

Earthquakes hit urban centres in Europe infrequently, but occasionally with disastrous effects. Obtaining an unbiased view of seismic hazard (and risk) is therefore very important. In principle, the best way to test probabilistic seismic hazard assessments (PSHAs) is to compare them with observations that are entirely independent of the procedure used to produce PSHA models. Arguably, the most valuable information in this context should be information on long-term hazard, namely maximum intensities (or magnitudes) occurring over time intervals that are at least as long as a seismic cycle. The new observations can provide information of maximum intensity (or magnitude) for long timescale as an input data for PSHA studies as well. Long-term information can be gained from intact stalagmites in natural caves. These formations survived all earthquakes that have occurred over thousands of years, depending on the age of the stalagmite. Their 'survival' requires that the horizontal ground acceleration (HGA) has never exceeded a certain critical value within that time period. Here, we present such a stalagmite-based case study from the Little Carpathians of Slovakia. A specially shaped, intact and vulnerable stalagmite in the Plavecká priepast cave was examined in 2013. This stalagmite is suitable for estimating the upper limit of horizontal peak ground acceleration generated by prehistoric earthquakes. The critical HGA values as a function of time going back into the past determined from the stalagmite that we investigated are presented. For example, at the time of Jóko event (1906), the critical HGA value cannot have been higher than 1 and 1.3 m/s2 at the time of the assumed Carnuntum event (∼340 AD), and 3000 years ago, it must have been lower than 1.7 m/s2. We claimed that the effect of Jóko earthquake (1906) on the location of the Plavecká priepast cave is consistent with the critical HGA value provided by the stalagmite we investigated. The approach used in this study yields significant new constraints on the seismic hazard, as tectonic structures close to Plavecká priepast cave did not generate strong earthquakes in the last few thousand years. The results of this study are highly relevant given that the two capitals, Vienna and Bratislava, are located within 40 and 70 km of the cave, respectively.

How well can we quantify dust deposition to the ocean?

Deposition of continental mineral aerosols (dust) in the Eastern Tropical North Atlantic Ocean, between the coast of Africa and the Mid-Atlantic Ridge, was estimated using several strategies based on the measurement of aerosols, trace metals dissolved in seawater, particulate material filtered from the water column, particles collected by sediment traps and sediments. Most of the data used in this synthesis involve samples collected during US GEOTRACES expeditions in 2010 and 2011, although some results from the literature are also used. Dust deposition generated by a global model serves as a reference against which the results from each observational strategy are compared. Observation-based dust fluxes disagree with one another by as much as two orders of magnitude, although most of the methods produce results that are consistent with the reference model to within a factor of 5. The large range of estimates indicates that further work is needed to reduce uncertainties associated with each method before it can be applied routinely to map dust deposition to the ocean. Calculated dust deposition using observational strategies thought to have the smallest uncertainties is lower than the reference model by a factor of 2-5, suggesting that the model may overestimate dust deposition in our study area.This article is part of the themed issue 'Biological and climatic impacts of ocean trace element chemistry'.

North Atlantic storm track changes during the Last Glacial Maximum recorded by Alpine speleothems.

The European Alps are an effective barrier for meridional moisture transport and are thus uniquely placed to record shifts in the North Atlantic storm track pattern associated with the waxing and waning of Late-Pleistocene Northern Hemisphere ice sheets. The lack of well-dated terrestrial proxy records spanning this time period, however, renders the reconstruction of past atmospheric patterns difficult. Here we present a precisely dated, continuous terrestrial record of meteoric precipitation in Europe between 30 and 14.7 ka. In contrast to present-day conditions, our speleothem data provide strong evidence for preferential advection of moisture from the South across the Alps supporting a southward shift of the storm track during the local Last Glacial Maximum (that is, 26.5-23.5 ka). Moreover, our age control indicates that this circulation pattern preceded the Northern Hemisphere precession maximum by ~3 ka, suggesting that obliquity may have played a considerable role in the Alpine ice aggradation.

Trends and oscillations in the Indian summer monsoon rainfall over the last two millennia.

Observations show that summer rainfall over large parts of South Asia has declined over the past five to six decades. It remains unclear, however, whether this trend is due to natural variability or increased anthropogenic aerosol loading over South Asia. Here we use stable oxygen isotopes in speleothems from northern India to reconstruct variations in Indian monsoon rainfall over the last two millennia. We find that within the long-term context of our record, the current drying trend is not outside the envelope of monsoon's oscillatory variability, albeit at the lower edge of this variance. Furthermore, the magnitude of multi-decadal oscillatory variability in monsoon rainfall inferred from our proxy record is comparable to model estimates of anthropogenic-forced trends of mean monsoon rainfall in the 21st century under various emission scenarios. Our results suggest that anthropogenic-forced changes in monsoon rainfall will remain difficult to detect against a backdrop of large natural variability.

Sea-level variability over five glacial cycles.

Research on global ice-volume changes during Pleistocene glacial cycles is hindered by a lack of detailed sea-level records for time intervals older than the last interglacial. Here we present the first robustly dated, continuous and highly resolved records of Red Sea sea level and rates of sea-level change over the last 500,000 years, based on tight synchronization to an Asian monsoon record. We observe maximum 'natural' (pre-anthropogenic forcing) sea-level rise rates below 2 m per century following periods with up to twice present-day ice volumes, and substantially higher rise rates for greater ice volumes. We also find that maximum sea-level rise rates were attained within 2 kyr of the onset of deglaciations, for 85% of such events. Finally, multivariate regressions of orbital parameters, sea-level and monsoon records suggest that major meltwater pulses account for millennial-scale variability and insolation-lagged responses in Asian monsoon records.

Early maximum extent of paleoglaciers from Mediterranean mountains during the last glaciation.

Mountain glaciers respond directly to changes in precipitation and temperature, thus their margin extent is a high-sensitivity climate proxy. Here, we present a robust (10)Be chronology for the glacier maximum areal extent of central Spain paleoglaciers dated at 26.1 ± 1.3 ka BP. These glaciers reached their maximum extent several thousand years earlier than those from central Europe due to the increased precipitation within a cold period between 25 to 29 ka BP, as confirmed by a local speleothem record. These paleoclimate conditions impacted the maximum extent of mountain glaciers along the western and central Mediterranean region. The cause and timing of the enhanced precipitation implies a southward shift of the North Atlantic Polar Front followed by storm tracks in response to changes in insolation via orbital parameters modulation. Thus, these mountain paleoglaciers from the Mediterranean region record an ocean-continent climate interaction triggered by external forcing.

Highly variable El Niño-Southern Oscillation throughout the Holocene.

The El Niño-Southern Oscillation (ENSO) drives large changes in global climate patterns from year to year, yet its sensitivity to continued anthropogenic greenhouse forcing is uncertain. We analyzed fossil coral reconstructions of ENSO spanning the past 7000 years from the Northern Line Islands, located in the center of action for ENSO. The corals document highly variable ENSO activity, with no evidence for a systematic trend in ENSO variance, which is contrary to some models that exhibit a response to insolation forcing over this same period. Twentieth-century ENSO variance is significantly higher than average fossil coral ENSO variance but is not unprecedented. Our results suggest that forced changes in ENSO, whether natural or anthropogenic, may be difficult to detect against a background of large internal variability.

The last glacial termination.

A major puzzle of paleoclimatology is why, after a long interval of cooling climate, each late Quaternary ice age ended with a relatively short warming leg called a termination. We here offer a comprehensive hypothesis of how Earth emerged from the last global ice age. A prerequisite was the growth of very large Northern Hemisphere ice sheets, whose subsequent collapse created stadial conditions that disrupted global patterns of ocean and atmospheric circulation. The Southern Hemisphere westerlies shifted poleward during each northern stadial, producing pulses of ocean upwelling and warming that together accounted for much of the termination in the Southern Ocean and Antarctica. Rising atmospheric CO2 during southern upwelling pulses augmented warming during the last termination in both polar hemispheres.

Abrupt change of Antarctic moisture origin at the end of Termination II.

The deuterium excess of polar ice cores documents past changes in evaporation conditions and moisture origin. New data obtained from the European Project for Ice Coring in Antarctica Dome C East Antarctic ice core provide new insights on the sequence of events involved in Termination II, the transition between the penultimate glacial and interglacial periods. This termination is marked by a north-south seesaw behavior, with first a slow methane concentration rise associated with a strong Antarctic temperature warming and a slow deuterium excess rise. This first step is followed by an abrupt north Atlantic warming, an abrupt resumption of the East Asian summer monsoon, a sharp methane rise, and a CO(2) overshoot, which coincide within dating uncertainties with the end of Antarctic optimum. Here, we show that this second phase is marked by a very sharp Dome C centennial deuterium excess rise, revealing abrupt reorganization of atmospheric circulation in the southern Indian Ocean sector.

Long-term neurodevelopmental effects of early detection and treatment in a 6-year-old patient with argininaemia diagnosed by newborn screening.

Newborn screening makes possible the early identification and treatment of asymptomatic ARG1-deficient patients; however, it is unknown whether early intervention prevents neurological insults. We identified a full-term Hispanic male infant with argininaemia by newborn screening with a serum arginine of 327 µmol/L (reference values 0-140); ARG1 was undetectable on enzyme assay. Sequence analysis of ARG1 revealed a heterozygous nonsense mutation, c.223A>T (p.K75X), and a novel heterozygous missense variant, c.425G>A (p.G142E). Dietary protein restriction began from age 3 months, with addition of sodium benzoate at 4 months, and carnitine from 14 months. For the past 6 years, his serum arginine concentrations were maintained between 268 and 763 µmol/L (reference values 10-140). He has normal development without spastic paraplegia, but with mild hepatomegaly and stable hepatic dysfunction. A full neurodevelopmental assessment was conducted at age 5 years. The BASC-2 rated the patient's behaviours as age-appropriate. The Leiter-R assessed his 'Fundamental Visualization', 'Sequential Order', and 'Picture Concept' at 'Average', 'Form Completion' and 'Matching' at 'Low Average', and 'Figure Ground' and 'Repeated Patterns' in the 'Deficit' range. The full-scale IQ and the functioning ability presented in the 'Borderline' range and in the 'Low Average' range, respectively. The VABS/Survey - Spanish Version showed difficulty in receptive and written language and fine and gross motor skills, and his performance to be at younger than his chronological age. The Short Sensory Profile showed some difficulty with taste and smell sensitivity. Long-term observation over 6 years in a patient with early treated argininaemia shows promising neurodevelopmental results.

Direct determination of the timing of sea level change during termination II.

An outcrop within the last interglacial terrace on Barbados contains corals that grew during the penultimate deglaciation, or Termination II. We used combined 230Th and 231Pa dating to determine that they grew 135.8 +/- 0.8 thousand years ago, indicating that sea level was 18 +/- 3 meters below present sea level at the time. This suggests that sea level had risen to within 20% of its peak last-interglacial value by 136 thousand years ago, in conflict with Milankovitch theory predictions. Orbital forcing may have played a role in the deglaciation, as may have isostatic adjustments due to large ice sheets. Other corals in the same outcrop grew during oxygen isotope (delta18O) substage 6e, indicating that sea level was 38 +/- 5 meters below present sea level, about 168.0 thousand years ago. When compared to the delta18O signal in the benthic V19-30/V19-28 record at that time, the coral data extend to the previous glacial cycle the conclusion that deep-water temperatures were colder during glacial periods.

A high-resolution absolute-dated late Pleistocene Monsoon record from Hulu Cave, China.

Oxygen isotope records of five stalagmites from Hulu Cave near Nanjing bear a remarkable resemblance to oxygen isotope records from Greenland ice cores, suggesting that East Asian Monsoon intensity changed in concert with Greenland temperature between 11,000 and 75,000 years before the present (yr. B.P.). Between 11,000 and 30,000 yr. B.P., the timing of changes in the monsoon, as established with 230Th dates, generally agrees with the timing of temperature changes from the Greenland Ice Sheet Project Two (GISP2) core, which supports GISP2's chronology in this interval. Our record links North Atlantic climate with the meridional transport of heat and moisture from the warmest part of the ocean where the summer East Asian Monsoon originates.

Efficacy of clarithromycin in preventing viridans streptococcal bacteremia following autologous stem cell transplantation.

BACKGROUND: In a study involving 200 patients, we previously found that 17.5% of patients developed viridans streptococcal (VS) bacteremia following autologous peripheral blood stem cell transplantation (aPBSCT) when ciprofloxacin or ciprofloxacin plus ampicillin was used for prophylaxis. PATIENTS AND METHODS: A retrospective evaluation of 100 consecutive recipients of aPBSCT was conducted to ascertain the incidence and outcome of VS bacteremia when a combination of ciprofLoxacin and clarithromycin was utilized for antimicrobiaL prophylaxis following transplantation. The 200 patients from our previous study, in which ciprofloxacin alone or ciprofloxacin with ampicillin was used for prophylaxis, were combined with the current group for the purpose of statistical analysis. RESULTS: Streptococcus mitis was isolated from the blood of five individuals at a median of 5 days following stem cell infusion. Each of these patients was neutropenic and presented with fever. Three isolates demonstrated intermediate resistance to macrolides in vitro. However, all episodes of bacteremia were treated successfully with systemic antibiotic therapy. CONCLUSION: Age, duration of neutropenia, type of underlying malignancy and type of conditioning chemotherapy regimen failed to have a significant impact on subsequent VS bacteremia. Only female sex and use of ciprofloxacin without clarithromycin as antimicrobiaL prophyLaxis predicted a significantly increased risk of VS bacteremia in both univariate and Logistic regression analyses.

Cytoreduction and stem cell mobilization with a regimen of paclitaxel, etoposide and cyclophosphamide followed by autologous transplantation using a preparative regimen of busulfan, etoposide and cyclophosphamide for patients with advanced lymphoma.

Forty-one patients with advanced Hodgkin's disease or intermediate or high-grade lymphoma, after having received standard salvage chemotherapy, were treated with a nonablative high-dose regimen of paclitaxel, etoposide and cyclophosphamide (D-TEC) to optimally cytoreduce their disease and simultaneously mobilize peripheral blood stem cells. This regimen produced a response rate of 78% (35% complete and 43.2% partial response) and mobilized sufficient peripheral blood stem cells in 94% of the patients. Thirty-two of these patients then underwent autologous progenitor cell transplantation after ablative conditioning with busulfan, etoposide and cyclophosphamide. Actuarial overall survival at 61 months was 71.9% with an event-free survival (EFS) of 65.6%. Median EFS was 24.4 months. EFS of patients responsive to salvage chemotherapy was 75% at 61 months, compared to 33.3% at 51.4 months in patients resistant to salvage chemotherapy. EFS of patients with disease sensitive to D-TEC was 75% at 61 months compared to 0% at 13.1 months in patients resistant to D-TEC. In a multivariate analysis, the only significant parameter for transplant outcome was sensitivity to D-TEC (p = 0.016), but not sensitivity to standard salvage chemotherapy. Aggressive cytoreduction may permit even those patients who are resistant to standard salvage chemotherapy to become successful transplant candidates.

Dexamethasone, paclitaxel, etoposide, cyclophosphamide (d-TEC) and G-CSF for stem cell mobilisation in multiple myeloma.

Forty-one patients with multiple myeloma were treated with a novel stem cell mobilisation regimen. The primary end points were adequate stem cell mobilising ability (>1% circulating CD34-positive cells) and collection (> or = 4 x 10(6) CD34-positive cells/kg), and safety. The secondary end point was activity against myeloma. The regimen (d-TEC) consisted of dexamethasone, paclitaxel 200 mg/m(2) i.v., etoposide 60 mg/kg i.v., cyclophosphamide 3 g/m(2) i.v., and G-CSF 5-10 microg/kg/day i.v. A total of 84 cycles were administered to these 41 individuals. Patient characteristics included a median age of 53 years, a median of five prior chemotherapy cycles, and a median interval of 10 months from diagnosis of myeloma to first cycle of d-TEC. Seventy-five percent of the patients had stage II or III disease, 50% had received carmustine and/or melphalan previously, and 25% had received prior radiation therapy. Eighty-eight percent of patients mobilised adequately after the first cycle of d-TEC and 91% mobilized adequately after the second cycle. An adequate number of stem cells were collected in 32 patients. Of the remaining nine patients, three mobilised, but stem cells were not collected, two mobilised but stem cell collection was < 4 x 10(6) CD34-positive cells/kg, three did not mobilise, and one died of disease progression. Major toxicities included pancytopenia, alopecia, fever and stomatitis. One patient died from multi-organ failure and progressive disease. Fifty percent of evaluable patients demonstrated a partial response and 28.6% of patients had a minor response. This novel dose-intense regimen was safe, capable of stem cell mobilisation and collection, even in heavily pre-treated patients, and active against the underlying myeloma.

Extremely large variations of atmospheric 14C concentration during the last glacial period.

A long record of atmospheric 14C concentration, from 45 to 11 thousand years ago (ka), was obtained from a stalagmite with thermal-ionization mass-spectrometric 230Th and accelerator mass-spectrometric 14C measurements. This record reveals highly elevated Delta14C between 45 and 33 ka, portions of which may correlate with peaks in cosmogenic 36Cl and 10Be isotopes observed in polar ice cores. Superimposed on this broad peak of Delta14C are several rapid excursions, the largest of which occurs between 44.3 and 43.3 ka. Between 26 and 11 ka, atmospheric Delta14C decreased from approximately 700 to approximately 100 per mil, modulated by numerous minor excursions. Carbon cycle models suggest that the major features of this record cannot be produced with solar or terrestrial magnetic field modulation alone but also require substantial fluctuations in the carbon cycle.