Modern temperatures in central-north Greenland warmest in past millennium.

The Greenland Ice Sheet has a central role in the global climate system owing to its size, radiative effects and freshwater storage, and as a potential tipping point1. Weather stations show that the coastal regions are warming2, but the imprint of global warming in the central part of the ice sheet is unclear, owing to missing long-term observations. Current ice-core-based temperature reconstructions3-5 are ambiguous with respect to isolating global warming signatures from natural variability, because they are too noisy and do not include the most recent decades. By systematically redrilling ice cores, we created a high-quality reconstruction of central and north Greenland temperatures from AD 1000 until 2011. Here we show that the warming in the recent reconstructed decade exceeds the range of the pre-industrial temperature variability in the past millennium with virtual certainty (P < 0.001) and is on average 1.5 ± 0.4 degrees Celsius (1 standard error) warmer than the twentieth century. Our findings suggest that these exceptional temperatures arise from the superposition of natural variability with a long-term warming trend, apparent since AD 1800. The disproportionate warming is accompanied by enhanced Greenland meltwater run-off, implying that anthropogenic influence has also arrived in central and north Greenland, which might further accelerate the overall Greenland mass loss.

North Pacific freshwater events linked to changes in glacial ocean circulation.

There is compelling evidence that episodic deposition of large volumes of freshwater into the oceans strongly influenced global ocean circulation and climate variability during glacial periods1,2. In the North Atlantic region, episodes of massive freshwater discharge to the North Atlantic Ocean were related to distinct cold periods known as Heinrich Stadials1-3. By contrast, the freshwater history of the North Pacific region remains unclear, giving rise to persistent debates about the existence and possible magnitude of climate links between the North Pacific and North Atlantic oceans during Heinrich Stadials4,5. Here we find that there was a strong connection between changes in North Atlantic circulation during Heinrich Stadials and injections of freshwater from the North American Cordilleran Ice Sheet to the northeastern North Pacific. Our record of diatom δ18O (a measure of the ratio of the stable oxygen isotopes 18O and 16O) over the past 50,000 years shows a decrease in surface seawater δ18O of two to three per thousand, corresponding to a decline in salinity of roughly two to four practical salinity units. This coincided with enhanced deposition of ice-rafted debris and a slight cooling of the sea surface in the northeastern North Pacific during Heinrich Stadials 1 and 4, but not during Heinrich Stadial 3. Furthermore, results from our isotope-enabled model6 suggest that warming of the eastern Equatorial Pacific during Heinrich Stadials was crucial for transmitting the North Atlantic signal to the northeastern North Pacific, where the associated subsurface warming resulted in a discernible freshwater discharge from the Cordilleran Ice Sheet during Heinrich Stadials 1 and 4. However, enhanced background cooling across the northern high latitudes during Heinrich Stadial 3-the coldest period in the past 50,000 years7-prevented subsurface warming of the northeastern North Pacific and thus increased freshwater discharge from the Cordilleran Ice Sheet. In combination, our results show that nonlinear ocean-atmosphere background interactions played a complex role in the dynamics linking the freshwater discharge responses of the North Atlantic and North Pacific during glacial periods.

Millennial-scale variability in Antarctic ice-sheet discharge during the last deglaciation.

Our understanding of the deglacial evolution of the Antarctic Ice Sheet (AIS) following the Last Glacial Maximum (26,000-19,000 years ago) is based largely on a few well-dated but temporally and geographically restricted terrestrial and shallow-marine sequences. This sparseness limits our understanding of the dominant feedbacks between the AIS, Southern Hemisphere climate and global sea level. Marine records of iceberg-rafted debris (IBRD) provide a nearly continuous signal of ice-sheet dynamics and variability. IBRD records from the North Atlantic Ocean have been widely used to reconstruct variability in Northern Hemisphere ice sheets, but comparable records from the Southern Ocean of the AIS are lacking because of the low resolution and large dating uncertainties in existing sediment cores. Here we present two well-dated, high-resolution IBRD records that capture a spatially integrated signal of AIS variability during the last deglaciation. We document eight events of increased iceberg flux from various parts of the AIS between 20,000 and 9,000 years ago, in marked contrast to previous scenarios which identified the main AIS retreat as occurring after meltwater pulse 1A and continuing into the late Holocene epoch. The highest IBRD flux occurred 14,600 years ago, providing the first direct evidence for an Antarctic contribution to meltwater pulse 1A. Climate model simulations with AIS freshwater forcing identify a positive feedback between poleward transport of Circumpolar Deep Water, subsurface warming and AIS melt, suggesting that small perturbations to the ice sheet can be substantially enhanced, providing a possible mechanism for rapid sea-level rise.

Ice sheet-free West Antarctica during peak early Oligocene glaciation.

One of Earth's most fundamental climate shifts, the greenhouse-icehouse transition 34 million years ago, initiated Antarctic ice sheet buildup, influencing global climate until today. However, the extent of the ice sheet during the Early Oligocene Glacial Maximum (~33.7 to 33.2 million years ago) that immediately followed this transition-a critical knowledge gap for assessing feedbacks between permanently glaciated areas and early Cenozoic global climate reorganization-is uncertain. In this work, we present shallow-marine drilling data constraining earliest Oligocene environmental conditions on West Antarctica's Pacific margin-a key region for understanding Antarctic ice sheet evolution. These data indicate a cool-temperate environment with mild ocean and air temperatures that prevented West Antarctic Ice Sheet formation. Climate-ice sheet modeling corroborates a highly asymmetric Antarctic ice sheet, thereby revealing its differential regional response to past and future climatic change.

Species formation through punctuated gradualism in planktonic foraminifera.

Detailed analysis of evolutionary changes in a 10-million-year long Late Neogene lineage of planktonic foraminifera has revealed a pattern that is not consistent with either the gradualistic or the punctuational model of evolution. The lineage was in stasis over a considerable part of its total duration but underwent relatively rapid, but not geologically instantaneous, gradual morphologic change that did not lead to lineage splitting. The term punctuated gradualism is suggested for this evolutionary modality.

Enhanced North Pacific deep-ocean stratification by stronger intermediate water formation during Heinrich Stadial 1.

The deglacial history of CO2 release from the deep North Pacific remains unresolved. This is due to conflicting indications about subarctic Pacific ventilation changes based on various marine proxies, especially for Heinrich Stadial 1 (HS-1) when a rapid atmospheric CO2 rise occurs. Here, we use a complex Earth System Model to investigate the deglacial North Pacific overturning and its control on ocean stratification. Our results show an enhanced intermediate-to-deep ocean stratification coeval with intensified North Pacific Intermediate Water (NPIW) formation during HS-1, compared to the Last Glacial Maximum. The stronger NPIW formation causes lower salinities and higher temperatures at intermediate depths. By lowering NPIW densities, this enlarges vertical density gradient and thus enhances intermediate-to-deep ocean stratification during HS-1. Physically, this process prevents the North Pacific deep waters from a better communication with the upper oceans, thus prolongs the existing isolation of glacial Pacific abyssal carbons during HS-1.

Targeting transcription-coupled nucleotide excision repair overcomes resistance in chronic lymphocytic leukemia.

Treatment resistance becomes a challenge at some point in the course of most patients with chronic lymphocytic leukemia (CLL). This applies to fludarabine-based regimens, and is also an increasing concern in the era of more targeted therapies. As cells with low-replicative activity rely on repair that triggers checkpoint-independent noncanonical pathways, we reasoned that targeting the nucleotide excision repair (NER) reaction addresses a vulnerability of CLL and might even synergize with fludarabine, which blocks the NER gap-filling step. We interrogated here especially the replication-independent transcription-coupled-NER ((TC)-NER) in prospective trial patients, primary CLL cultures, cell lines and mice. We screen selected (TC)-NER-targeting compounds as experimental (illudins) or clinically approved (trabectedin) drugs. They inflict transcription-stalling DNA lesions requiring TC-NER either for their removal (illudins) or for generation of lethal strand breaks (trabectedin). Genetically defined systems of NER deficiency confirmed their specificity. They selectively and efficiently induced cell death in CLL, irrespective of high-risk cytogenetics, IGHV status or clinical treatment history, including resistance. The substances induced ATM/p53-independent apoptosis and showed marked synergisms with fludarabine. Trabectedin additionally perturbed stromal-cell protection and showed encouraging antileukemic profiles even in aggressive and transforming murine CLL. This proof-of-principle study established (TC)-NER as a mechanism to be further exploited to resensitize CLL cells.

Linkages between atmospheric blocking, sea ice export through Fram Strait and the Atlantic Meridional Overturning Circulation.

As a key persistent component of the atmospheric dynamics, the North Atlantic blocking activity has been linked to extreme climatic phenomena in the European sector. It has also been linked to Atlantic multidecadal ocean variability, but its potential links to rapid oceanic changes have not been investigated. Using a global ocean-sea ice model forced with atmospheric reanalysis data, here it is shown that the 1962-1966 period of enhanced blocking activity over Greenland resulted in anomalous sea ice accumulation in the Arctic and ended with a sea ice flush from the Arctic into the North Atlantic Ocean through Fram Strait. This event induced a significant decrease of Labrador Sea water surface salinity and an abrupt weakening of the Atlantic Meridional Overturning Circulation (AMOC) during the 1970s. These results have implications for the prediction of rapid AMOC changes and indicate that an important part of the atmosphere-ocean dynamics at mid- and high latitudes requires a proper representation of the Fram Strait sea ice transport and of the synoptic scale variability such as atmospheric blocking, which is a challenge for current coupled climate models.

Supine hypotensive syndrome.

OBJECTIVE: To review reports of the supine hypotensive syndrome with reference to clinical presentation, suggestions on the mechanism of onset, and the possibility of advance detection. DATA SOURCES: We used worldwide obstetric, anesthesia, and general medical journals from 1922 onward, a Medline search from 1966 onward, and manual cross-referencing for prior publications. METHODS OF STUDY SELECTION: We selected approximately 100 case reports of supine hypotensive syndrome and studies on supine blood pressure responses during late pregnancy. DATA EXTRACTION AND SYNTHESIS: Publications that recorded novel clinical observations, specific hemodynamic or biochemical measurements, or associated complications were included. CONCLUSIONS: Supine hypotensive syndrome is characterized by severe supine symptoms and hypotension in late pregnancy, which compel the unconstrained subject to change position. Rarely, it may manifest even from the fifth month of pregnancy or postpartum, as well as in the pelvic tilt or sitting positions. Although inferior vena cava compression, influenced primarily by the size of the uterus and exact maternal and fetal position, is the major determinant in its development, other factors may also be important in modulating the circulatory effects of such compression. Advance recognition of susceptibility to the syndrome depends on a history of severe supine symptoms or supine intolerance and an increase in maternal heart rate and decrease in pulse pressure in the supine position. As there seems to be a spectrum of severity from minimal central cardiovascular alterations to severe syncopal shock resulting from supine inferior vena cava compression, it is difficult to define a cutoff point at which the syndrome occurs. Although usually recognizable by maternal symptoms, severe hypotension without symptoms has been reported on three occasions.

Extracting line representations of sulcal and gyral patterns in MR images of the human brain.

This paper describes automatic procedures for extracting sulcal and gyral patterns from magnetic resonance (MR) images of the human brain. Specifically, we present three algorithms for the extraction of gyri, sulci, and sulcal fundi. These algorithms yield highly condensed line representations which can be used to describe the individual properties of the neocortical surface. The algorithms consist of a sequence of image analysis steps applied directly to the volumetric image data without requiring intermediate data representations such as surfaces or three-dimensional renderings. Previous studies have mostly focused on the extraction of surface representations, rather than line representations of cortical structures. We believe that line representations provide a valuable alternative to surface representations.

Automatic labelling of the human cortical surface using sulcal basins.

Human brain mapping aims at establishing correspondences between brain function and brain anatomy. One of the most intriguing problems in this field is the high interpersonal variability of human neuroanatomy which makes studies across many subjects very difficult. The cortical folds ('sulci') often serve as landmarks that help to establish correspondences between subjects. In this paper, we will present a method that automatically detects and attributes neuroanatomical names to the cortical folds using image analysis methods applied to magnetic resonance data of human brains. We claim that the cortical folds can be subdivided into a number of substructures which we call sulcal basins. The concept of sulcal basins allows us to establish a complete parcellation of the cortical surface into separate regions. These regions are neuroanatomically meaningful and can be identified from MR data sets across many subjects. Sulcal basins are segmented using a region growing approach. The automatic labelling is achieved by a model matching technique.

LIPSIA--a new software system for the evaluation of functional magnetic resonance images of the human brain.

This paper describes the non-commercial software system LIPSIA that was developed for the processing of functional magnetic resonance images (fMRI) of the human brain. The analysis of fMRI data comprises various aspects including filtering, spatial transformation, statistical evaluation as well as segmentation and visualization. In LIPSIA, particular emphasis was placed on the development of new visualization and segmentation techniques that support visualizations of individual brain anatomy so that experts can assess the exact location of activation patterns in individual brains. As the amount of data that must be handled is enormous, another important aspect in the development LIPSIA was the efficiency of the software implementation. Well established statistical techniques were used whenever possible.

Evidence for obliquity forcing of glacial Termination II.

Variations in the intensity of high-latitude Northern Hemisphere summer insolation, driven largely by precession of the equinoxes, are widely thought to control the timing of Late Pleistocene glacial terminations. However, recently it has been suggested that changes in Earth's obliquity may be a more important mechanism. We present a new speleothem-based North Atlantic marine chronology that shows that the penultimate glacial termination (Termination II) commenced 141,000 +/- 2500 years before the present, too early to be explained by Northern Hemisphere summer insolation but consistent with changes in Earth's obliquity. Our record reveals that Terminations I and II are separated by three obliquity cycles and that they started at near-identical obliquity phases.

A construction of an averaged representation of human cortical gyri using non-linear principal component analysis.

Because of the complex shape of human cortical gyri and great variation between individuals, development of effective representation schemes which allow establishment of correspondence between individuals, extraction of average structure of a population, and co-registration has proved very difficult. We introduce an approach which extracts line representations of gyri at different depths from high resolution MRI, labels main gyri semi-automatically, and extracts a template from a population using non-linear principal component analysis. The method has been tested on data from 96 healthy human volunteers. The model captures the most salient shape features of all major cortical gyri, and can be used for inter-subject registration, for investigating regionalized inter-subject variability, and for inter-hemispheric comparisons.

Revisiting the role of Broca's area in sentence processing: syntactic integration versus syntactic working memory.

Most previous neuroimaging studies of sentence processing have associated Broca's area with syntactic processing; however, the exact nature of the processes subserved by this brain region is yet not well understood. Although some authors suggest that Brodmann area (BA) 44 of the left inferior frontal gyrus (i.e., Broca's area) is relevant for syntactic integration processes, others claim that it is associated with working memory mechanisms relevant for language processing. To dissociate these two possible functions, the present study investigated hemodynamic responses elicited while participants processed German indirect wh-questions. Activation increases were observed in left BA 44 together with superior temporal areas and right hemispheric homologues for sentences with noncanonical word order, in which a verb argument was dislocated from its canonical position over a relatively long distance. In these sentences, syntactic working memory load was assumed to be greatest. In contrast, no activation increase was elicited by object-initial as opposed to subject-initial sentences that did not differ with respect to working memory costs but with respect to syntactic integration costs. These data strongly suggest that Broca's area plays a critical role in syntactic working memory during online sentence comprehension.

Sulcal variability of twins.

We investigated three-dimensional, depth-encoded line representations of neocortical sulci calculated from magnetic resonance image (MRI) datasets of 19 pairs of normal monozygotic twins. Monozygotic co-twins were significantly more alike than control pairs of unrelated twins matched from the same sample. Sulcal depth influenced sulcal similarity, with deeper sulci being more similar than superficial sulci. This was true both for the pairs of related co-twins and for the unrelated pairs, although the sulcal depth effect was stronger for the related twins. Our results indicate that the shape of deep (ontogenetically early) sulci of the human brain is more strongly predetermined than that of superficial sulci. The finding that sulcal similarity increased with sulcal depth especially within monozygotic twin pairs should stimulate further investigations of the relative importance of genetic versus shared environmental morphogenetic factors that must account for this result. In addition, we found that subjects with similar brain shape also have more similar sulcal patterns, suggesting that both features are the result of ontogenetically related processes. Sulcal comparisons across the entire sample suggested that the left posterior lateral hemispheric surface may be the least variable brain area. Methodologically, these results were obtained by the representation of sulci as three-dimensional polygonal lines (termed 'sulcal cuts') that are extracted automatically from MRI data sets using new image analysis techniques.

A physician questionnaire study of the net cost of computerized tomographic scanning.

This paper reports the results of a physician questionnaire study of the net cost impact of CT Scanning on the health care system. The study objective is accomplished by questioning physicians, on a case-by-case basis, on the number and type of diagnostic tests and hospital care which would have been provided in lieu of CT. These findings indicate that CT Scanning, while expensive on a per use basis, results in significant cost savings on a per case basis because it eliminates the need for multiple alternative tests and hospital stays. Finally, the controversy over the cost of CT Scanning is attributed not to the intrinsic merits of CT but rather to structural elements within the health care system which create disincentives to economize.

On multivariate spectral analysis of fMRI time series.

Most of functional magnetic resonance imaging (fMRI) time series analysis is based on single voxel data evaluation using parametric statistical tests. The result of such an analysis is a statistical parametric map. Voxels with a high significance value in the parametric test are interpreted as activation regions stimulated by the experimental task. However, for the investigation of functional connectivities it would be interesting to get some detailed information about the temporal dynamics of the blood oxygen level-dependent (BOLD) signal. For investigating that behavior, a method for fMRI data analysis has been developed that is based on Wiener theory of spectral analysis for multivariate time series. Spectral parameters such as coherence measure and phase lead can be estimated. The resulting maps give detailed information on brain regions that belong to a network structure and also show the temporal behavior of the BOLD response function. This paper describes the method and presents a visual fMRI experiment as an example to demonstrate the results.