Change of the condyle-position in maximum intercuspidation during digital, clinical occlusal analysis

Digital analysis of the occlusal contacts can be performed with the T-scan device (T Scan III, TekScan, Boston, USA). However, the thickness of the interocclusal T-scan sheet (100 μm) may lead to a displacement of the mandible. Thus, the aim of this study was to investigate the impact of the T-scan sheet on the position of the mandibular condyles in maximum intercuspidation. Twenty dentate subjects with healthy jaw function were enrolled in the study. An ultrasonic axiography device was used to measure the position of the condyles. Ten 3D condyle positions in maximum intercuspidation of the teeth were recorded: first the reference position without the sheet, then 3 times without the sheet, 3 times with the sheet, and finally again 3 times without the sheet. There was a statistically significant difference (Wilcoxon matched pairs test) between the condyle positions with and without the interocclusally positioned T-scan sheet (P < 0.0005). The T-scan device lead to a displacement of the condyles of about 1 mm mainly in ventral direction (P = 0.005). Thus, occlusal analysis is not performed in physiological, maximum intercuspidation. This has to be considered when interpreting the measured contact points.

Glacier response to the change in atmospheric circulation in the eastern Mediterranean during the Last Glacial Maximum

In this study, we document glacial deposits and reconstruct the glacial history in the Karagöl valley system in the eastern Uludağ in northwestern Turkey based on 42 cosmogenic 10Be exposure ages from boulders and bedrock. Our results suggest the Last Glacial Maximum (LGM) advance prior to 20.4 ± 1.2 ka and at least three re-advances until 18.6 ± 1.2 ka during the global LGM within Marine Isotope Stage-2. In addition, two older advances of unknown age are geomorphologically well constrained, but not dated due to the absence of suitable boulders. Glaciers advanced again two times during the Lateglacial. The older is exposure dated to not later than 15.9 ± 1.1 ka and the younger is attributed to the Younger Dryas (YD) based on field evidence. The timing of the glaciations in the Karagöl valley correlates well with documented archives in the Anatolian and Mediterranean mountains and the Alps. These glacier fluctuations may be explained by the change in the atmospheric circulation pattern during the different phases of North Atlantic Oscillation (NAO) winter indices.

Thoracic target volume delineation using various maximum-intensity projection computed tomography image sets for stereotactic body radiation therapy

The motion of lung tumors during respiration makes the accurate delivery of radiation therapy to the thorax difficult because it increases the uncertainty of target position. The adoption of four-dimensional computed tomography (4D-CT) has allowed us to determine how a tumor moves with respiration for each individual patient. Using information acquired during a 4D-CT scan, we can define the target, visualize motion, and calculate dose during the planning phase of the radiotherapy process. One image data set that can be created from the 4D-CT acquisition is the maximum-intensity projection (MIP). The MIP can be used as a starting point to define the volume that encompasses the motion envelope of the moving gross target volume (GTV). Because of the close relationship that exists between the MIP and the final target volume, we investigated four MIP data sets created with different methodologies (3 using various 4D-CT sorting implementations, and one using all available cine CT images) to compare target delineation. It has been observed that changing the 4D-CT sorting method will lead to the selection of a different collection of images; however, the clinical implications of changing the constituent images on the resultant MIP data set are not clear. There has not been a comprehensive study that compares target delineation based on different 4D-CT sorting methodologies in a patient population. We selected a collection of patients who had previously undergone thoracic 4D-CT scans at our institution, and who had lung tumors that moved at least 1 cm. We then generated the four MIP data sets and automatically contoured the target volumes. In doing so, we identified cases in which the MIP generated from a 4D-CT sorting process under-represented the motion envelope of the target volume by more than 10% than when measured on the MIP generated from all of the cine CT images. The 4D-CT methods suffered from duplicate image selection and might not choose maximum extent images. Based on our results, we suggest utilization of a MIP generated from the full cine CT data set to ensure a representative inclusive tumor extent, and to avoid geometric miss.

An Innovative Phase I Trial Design Allowing for the Identification of Multiple Potential Maximum Tolerated Doses with Combination Therapy of Targeted Agents

Treatment for cancer often involves combination therapies used both in medical practice and clinical trials. Korn and Simon listed three reasons for the utility of combinations: 1) biochemical synergism, 2) differential susceptibility of tumor cells to different agents, and 3) higher achievable dose intensity by exploiting non-overlapping toxicities to the host. Even if the toxicity profile of each agent of a given combination is known, the toxicity profile of the agents used in combination must be established. Thus, caution is required when designing and evaluating trials with combination therapies. Traditional clinical design is based on the consideration of a single drug. However, a trial of drugs in combination requires a dose-selection procedure that is vastly different than that needed for a single-drug trial. When two drugs are combined in a phase I trial, an important trial objective is to determine the maximum tolerated dose (MTD). The MTD is defined as the dose level below the dose at which two of six patients experience drug-related dose-limiting toxicity (DLT). In phase I trials that combine two agents, more than one MTD generally exists, although all are rarely determined. For example, there may be an MTD that includes high doses of drug A with lower doses of drug B, another one for high doses of drug B with lower doses of drug A, and yet another for intermediate doses of both drugs administered together. With classic phase I trial designs, only one MTD is identified. Our new trial design allows identification of more than one MTD efficiently, within the context of a single protocol. The two drugs combined in our phase I trial are temsirolimus and bevacizumab. Bevacizumab is a monoclonal antibody targeting the vascular endothelial growth factor (VEGF) pathway which is fundamental for tumor growth and metastasis. One mechanism of tumor resistance to antiangiogenic therapy is upregulation of hypoxia inducible factor 1α (HIF-1α) which mediates responses to hypoxic conditions. Temsirolimus has resulted in reduced levels of HIF-1α making this an ideal combination therapy. Dr. Donald Berry developed a trial design schema for evaluating low, intermediate and high dose levels of two drugs given in combination as illustrated in a recently published paper in Biometrics entitled “A Parallel Phase I/II Clinical Trial Design for Combination Therapies.” His trial design utilized cytotoxic chemotherapy. We adapted this design schema by incorporating greater numbers of dose levels for each drug. Additional dose levels are being examined because it has been the experience of phase I trials that targeted agents, when given in combination, are often effective at dosing levels lower than the FDA-approved dose of said drugs. A total of thirteen dose levels including representative high, intermediate and low dose levels of temsirolimus with representative high, intermediate, and low dose levels of bevacizumab will be evaluated. We hypothesize that our new trial design will facilitate identification of more than one MTD, if they exist, efficiently and within the context of a single protocol. Doses gleaned from this approach could potentially allow for a more personalized approach in dose selection from among the MTDs obtained that can be based upon a patient’s specific co-morbid conditions or anticipated toxicities.

Transient simulations of the carbon and nitrogen dynamics in northern peatlands: from the Last Glacial Maximum to the 21st century

The development of northern high-latitude peatlands played an important role in the carbon (C) balance of the land biosphere since the Last Glacial Maximum (LGM). At present, carbon storage in northern peatlands is substantial and estimated to be 500 ± 100 Pg C (1 Pg C = 1015 g C). Here, we develop and apply a peatland module embedded in a dynamic global vegetation and land surface process model (LPX-Bern 1.0). The peatland module features a dynamic nitrogen cycle, a dynamic C transfer between peatland acrotelm (upper oxic layer) and catotelm (deep anoxic layer), hydrology- and temperature-dependent respiration rates, and peatland specific plant functional types. Nitrogen limitation down-regulates average modern net primary productivity over peatlands by about half. Decadal acrotelm-to-catotelm C fluxes vary between −20 and +50 g C m−2 yr−1 over the Holocene. Key model parameters are calibrated with reconstructed peat accumulation rates from peat-core data. The model reproduces the major features of the peat core data and of the observation-based modern circumpolar soil carbon distribution. Results from a set of simulations for possible evolutions of northern peat development and areal extent show that soil C stocks in modern peatlands increased by 365–550 Pg C since the LGM, of which 175–272 Pg C accumulated between 11 and 5 kyr BP. Furthermore, our simulations suggest a persistent C sequestration rate of 35–50 Pg C per 1000 yr in present-day peatlands under current climate conditions, and that this C sink could either sustain or turn towards a source by 2100 AD depending on climate trajectories as projected for different representative greenhouse gas concentration pathways.

A reconstruction of atmospheric carbon dioxide and its stable carbon isotopic composition from the penultimate glacial maximum to the last glacial inception

The reconstruction of the stable carbon isotope evolution in atmospheric CO2 (δ13Catm), as archived in Antarctic ice cores, bears the potential to disentangle the contributions of the different carbon cycle fluxes causing past CO2 variations. Here we present a new record of δ13Catm before, during and after the Marine Isotope Stage 5.5 (155 000 to 105 000 yr BP). The dataset is archived on the data repository PANGEA® (www.pangea.de) under 10.1594/PANGAEA.817041. The record was derived with a well established sublimation method using ice from the EPICA Dome C (EDC) and the Talos Dome ice cores in East Antarctica. We find a 0.4‰ shift to heavier values between the mean δ13Catm level in the Penultimate (~ 140 000 yr BP) and Last Glacial Maximum (~ 22 000 yr BP), which can be explained by either (i) changes in the isotopic composition or (ii) intensity of the carbon input fluxes to the combined ocean/atmosphere carbon reservoir or (iii) by long-term peat buildup. Our isotopic data suggest that the carbon cycle evolution along Termination II and the subsequent interglacial was controlled by essentially the same processes as during the last 24 000 yr, but with different phasing and magnitudes. Furthermore, a 5000 yr lag in the CO2 decline relative to EDC temperatures is confirmed during the glacial inception at the end of MIS5.5 (120 000 yr BP). Based on our isotopic data this lag can be explained by terrestrial carbon release and carbonate compensation.

Antarctic Glacial History Since the Last Glacial Maximum: An Overview of the Record on Land

This overview examines available circum-Antarctic glacial history archives on land, related to developments after the Last Glacial Maximum (LGM). It considers the glacial-stratigraphic and morphologic records and also biostratigraphical information from moss banks, lake sediments and penguin rookeries, with some reference to relevant glacial marine records. It is concluded that Holocene environmental development in Antarctica differed from that in the Northern Hemisphere. The initial deglaciation of the shelf areas surrounding Antarctica took place before 10000 C-14 yrs before present(sp), and was controlled by rising global sea level. This was followed by the deglaciation of some presently ice-free inner shelf and land areas between 10000 and 8000 yr sp. Continued deglaciation occurred gradually between 8000 yr sp and 5000 yr sp. Mid-Holocene glacial readvances are recorded from various sites around Antarctica. There are strong indications of a circum-Antarctic climate warmer than today 4700-2000 yr sp. The best dated records from the Antarctic Peninsula and coastal Victoria Land suggest climatic optimums there from 4000-3000 yr sp and 3600-2600 yr sp, respectively. Thereafter Neoglacial readvances are recorded. Relatively limited glacial expansions in Antarctica during the past few hundred years correlate with the Little Ice Age in the Northern Hemisphere.

Terrestrial and submarine evidence for the extent and timing of the Last Glacial Maximum and the onset of deglaciation on the maritime-Antarctic and sub-Antarctic islands

This paper is the maritime and sub–Antarctic contribution to the Scientific Committee for Antarctic Research (SCAR) Past Antarctic Ice Sheet Dynamics (PAIS) community Antarctic Ice Sheet reconstruction. The overarching aim for all sectors of Antarctica was to reconstruct the Last Glacial Maximum (LGM) ice sheet extent and thickness, and map the subsequent deglaciation in a series of 5000 year time slices. However, our review of the literature found surprisingly few high quality chronological constraints on changing glacier extents on these timescales in the maritime and sub–Antarctic sector. Therefore, in this paper we focus on an assessment of the terrestrial and offshore evidence for the LGM ice extent, establishing minimum ages for the onset of deglaciation, and separating evidence of deglaciation from LGM limits from those associated with later Holocene glacier fluctuations. Evidence included geomorphological descriptions of glacial landscapes, radiocarbon dated basal peat and lake sediment deposits, cosmogenic isotope ages of glacial features and molecular biological data. We propose a classification of the glacial history of the maritime and sub–Antarctic islands based on this assembled evidence. These include: (Type I) islands which accumulated little or no LGM ice; (Type II) islands with a limited LGM ice extent but evidence of extensive earlier continental shelf glaciations; (Type III) seamounts and volcanoes unlikely to have accumulated significant LGM ice cover; (Type IV) islands on shallow shelves with both terrestrial and submarine evidence of LGM (and/or earlier) ice expansion; (Type V) Islands north of the Antarctic Polar Front with terrestrial evidence of LGM ice expansion; and (Type VI) islands with no data. Finally, we review the climatological and geomorphological settings that separate the glaciological history of the islands within this classification scheme.

A community-based geological reconstruction of Antarctic Ice Sheet deglaciation since the Last Glacial Maximum

A robust understanding of Antarctic Ice Sheet deglacial history since the Last Glacial Maximum is important in order to constrain ice sheet and glacial-isostatic adjustment models, and to explore the forcing mechanisms responsible for ice sheet retreat. Such understanding can be derived from a broad range of geological and glaciological datasets and recent decades have seen an upsurge in such data gathering around the continent and Sub-Antarctic islands. Here, we report a new synthesis of those datasets, based on an accompanying series of reviews of the geological data, organised by sector. We present a series of timeslice maps for 20 ka, 15 ka, 10 ka and 5 ka, including grounding line position and ice sheet thickness changes, along with a clear assessment of levels of confidence. The reconstruction shows that the Antarctic Ice sheet did not everywhere reach the continental shelf edge at its maximum, that initial retreat was asynchronous, and that the spatial pattern of deglaciation was highly variable, particularly on the inner shelf. The deglacial reconstruction is consistent with a moderate overall excess ice volume and with a relatively small Antarctic contribution to meltwater pulse 1a. We discuss key areas of uncertainty both around the continent and by time interval, and we highlight potential priorities for future work. The synthesis is intended to be a resource for the modelling and glacial geological community.