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.

Cardiovascular complications of conventional and targeted adjuvant breast cancer therapy

Adjuvant therapy has improved the survival of women with early breast cancer (BC). Meta-analyses suggest that anthracycline-based regimens reduced the annual BC death rate by 40% in women below the age of 50 and 20% in older women. Novel agents designed to modulate abnormal growth factor signaling in and around the BC cell further increase patients' chances of survival. However, both conventional chemotherapeutic agents as well as some of the novel signaling inhibitors can induce important cardiovascular side-effects, potentially attenuating the progress made in recent years. The mechanism of cancer drug-induced cardiovascular complications varies greatly with some compounds inducing irreversible myocardial cell damage, while others lead to temporary cell dysfunction. The challenge of the future will be to prospectively discriminate between irreversible damage which can lead to progressive cardiovascular disease and reversible cardiovascular dysfunctions without further prognostic implications. Since adjuvant therapy for BC is potentially curative, emphasis must be placed on finding treatments combining maximum efficacy with the minimum of long-term side-effects in order to achieve survival with preserved quality of life.

Deep ocean ventilation, carbon isotopes, marine sedimentation and the deglacial CO2 rise

The link between the atmospheric CO2 level and the ventilation state of the deep ocean is an important building block of the key hypotheses put forth to explain glacial-interglacial CO2 fluctuations. In this study, we systematically examine the sensitivity of atmospheric CO2 and its carbon isotope composition to changes in deep ocean ventilation, the ocean carbon pumps, and sediment formation in a global three-dimensional ocean-sediment carbon cycle model. Our results provide support for the hypothesis that a break up of Southern Ocean stratification and invigorated deep ocean ventilation were the dominant drivers for the early deglacial CO2 rise of ~35 ppm between the Last Glacial Maximum and 14.6 ka BP. Another rise of 10 ppm until the end of the Holocene is attributed to carbonate compensation responding to the early deglacial change in ocean circulation. Our reasoning is based on a multi-proxy analysis which indicates that an acceleration of deep ocean ventilation during the early deglaciation is not only consistent with recorded atmospheric CO2 but also with the reconstructed opal sedimentation peak in the Southern Ocean at around 16 ka BP, the record of atmospheric δ13CCO2, and the reconstructed changes in the Pacific CaCO3 saturation horizon.

Clazosentan: prevention of cerebral vasospasm and the potential to overcome infarction

Cerebral vasospasm is a common complication occurring after aneurysmal subarachnoid hemorrhage (SAH). It is recognized as a leading preventable cause of morbidity and mortality in this patient group, but its management is challenging, and new treatments are needed. Clazosentan is an endothelin receptor antagonist designed to prevent endothelin-mediated cerebral vasospasm. Vajkoczy et al. (Neurosurg 103:9-17, 2005) initially demonstrated that clazosentan reduced moderate/severe angiographically proven vasospasm by 55% relative to placebo. These findings led to the initiation of the CONSCIOUS trial program to further examine the efficacy and safety of clazosentan in reducing angiographic vasospasm and improving clinical outcome after aneurysmal SAH. In the first of these studies, CONSCIOUS-1, 413 patients were randomized to placebo or clazosentan 1, 5 or 15 mg/h. Clazosentan reduced angiographic vasospasm dose-dependently relative to placebo with a maximum risk reduction of 65% with the highest dose. Despite this, there was no benefit of clazosentan on the secondary protocol-defined morbidity/mortality endpoint; however, additional post-hoc and modified endpoint analyses provided some evidence for a potential clinical benefit. Two additional large-scale studies (CONSCIOUS-2 and CONSCIOUS-3) are now underway to further investigate the potential of clazosentan to improve long-term clinical outcome.

Deep ocean ventilation, carbon isotopes, marine sedimentation and the deglacial CO2 rise

The link between the atmospheric CO2 level and the ventilation state of the deep ocean is an important building block of the key hypotheses put forth to explain glacial-interglacial CO2 fluctuations. In this study, we systematically examine the sensitivity of atmospheric CO2 and its carbon isotope composition to changes in deep ocean ventilation, the ocean carbon pumps, and sediment formation in a global 3-D ocean-sediment carbon cycle model. Our results provide support for the hypothesis that a break up of Southern Ocean stratification and invigorated deep ocean ventilation were the dominant drivers for the early deglacial CO2 rise of ~35 ppm between the Last Glacial Maximum and 14.6 ka BP. Another rise of 10 ppm until the end of the Holocene is attributed to carbonate compensation responding to the early deglacial change in ocean circulation. Our reasoning is based on a multi-proxy analysis which indicates that an acceleration of deep ocean ventilation during early deglaciation is not only consistent with recorded atmospheric CO2 but also with the reconstructed opal sedimentation peak in the Southern Ocean at around 16 ka BP, the record of atmospheric δ13CCO2, and the reconstructed changes in the Pacific CaCO3 saturation horizon.

In situ cardiac performance of Atlantic cod (Gadus morhua) at cold temperatures: long-term acclimation, acute thermal challenge and the role of adrenaline

The resting and maximum in situ cardiac performance of Newfoundland Atlantic cod (Gadus morhua) acclimated to 10, 4 and 0°C were measured at their respective acclimation temperatures, and when acutely exposed to temperature changes: i.e. hearts from 10°C fish cooled to 4°C, and hearts from 4°C fish measured at 10 and 0°C. Intrinsic heart rate (f(H)) decreased from 41 beats min(-1) at 10°C to 33 beats min(-1) at 4°C and 25 beats min(-1) at 0°C. However, this degree of thermal dependency was not reflected in maximal cardiac output (Q(max) values were ~44, ~37 and ~34 ml min(-1) kg(-1) at 10, 4 and 0°C, respectively). Further, cardiac scope showed a slight positive compensation between 4 and 0°C (Q(10)=1.7), and full, if not a slight over compensation between 10 and 4°C (Q(10)=0.9). The maximal performance of hearts exposed to an acute decrease in temperature (i.e. from 10 to 4°C and 4 to 0°C) was comparable to that measured for hearts from 4°C- and 0°C-acclimated fish, respectively. In contrast, 4°C-acclimated hearts significantly out-performed 10°C-acclimated hearts when tested at a common temperature of 10°C (in terms of both Q(max) and power output). Only minimal differences in cardiac function were seen between hearts stimulated with basal (5 nmol l(-1)) versus maximal (200 nmol l(-1)) levels of adrenaline, the effects of which were not temperature dependent. These results: (1) show that maximum performance of the isolated cod heart is not compromised by exposure to cold temperatures; and (2) support data from other studies, which show that, in contrast to salmonids, cod cardiac performance/myocardial contractility is not dependent upon humoral adrenergic stimulation.

Evaluation of administration of isoflurane at approximately the minimum alveolar concentration on depression of a nociceptive withdrawal reflex evoked by transcutaneous electrical stimulation in ponies

OBJECTIVE: To investigate effects of isoflurane at approximately the minimum alveolar concentration (MAC) on the nociceptive withdrawal reflex (NWR) of the forelimb of ponies as a method for quantifying anesthetic potency. ANIMALS: 7 healthy adult Shetland ponies. PROCEDURE: Individual MAC (iMAC) for isoflurane was determined for each pony. Then, effects of isoflurane administered at 0.85, 0.95, and 1.05 iMAC on the NWR were assessed. At each concentration, the NWR threshold was defined electromyographically for the common digital extensor and deltoid muscles by stimulating the digital nerve; additional electrical stimulations (3, 5, 10, 20, 30, and 40 mA) were delivered, and the evoked activity was recorded and analyzed. After the end of anesthesia, the NWR threshold was assessed in standing ponies. RESULTS: Mean +/- SD MAC of isoflurane was 1.0 +/- 0.2%. The NWR thresholds for both muscles increased significantly in a concentration-dependent manner during anesthesia, whereas they decreased in awake ponies. Significantly higher thresholds were found for the deltoid muscle, compared with thresholds for the common digital extensor muscle, in anesthetized ponies. At each iMAC tested, amplitudes of the reflex responses from both muscles increased as stimulus intensities increased from 3 to 40 mA. A concentration-dependent depression of evoked reflexes with reduction in slopes of the stimulus-response functions was detected. CONCLUSIONS AND CLINICAL RELEVANCE: Anesthetic-induced changes in sensory-motor processing in ponies anesthetized with isoflurane at concentrations of approximately 1.0 MAC can be detected by assessment of NWR. This method will permit comparison of effects of inhaled anesthetics or anesthetic combinations on spinal processing in equids.

A systematic review on the accuracy and the clinical outcome of computer-guided template-based implant dentistry

Introduction: The aim of this systematic review was to analyze the dental literature regarding accuracy and clinical application in computer-guided template-based implant dentistry. Materials and methods: An electronic literature search complemented by manual searching was performed to gather data on accuracy and surgical, biological and prosthetic complications in connection with computer-guided implant treatment. For the assessment of accuracy meta-regression analysis was performed. Complication rates are descriptively summarized. Results: From 3120 titles after the literature search, eight articles met the inclusion criteria regarding accuracy and 10 regarding the clinical performance. Meta-regression analysis revealed a mean deviation at the entry point of 1.07 mm (95% CI: 0.76-1.22 mm) and at the apex of 1.63 mm (95% CI: 1.26-2 mm). No significant differences between the studies were found regarding method of template production or template support and stabilization. Early surgical complications occurred in 9.1%, early prosthetic complications in 18.8% and late prosthetic complications in 12% of the cases. Implant survival rates of 91-100% after an observation time of 12-60 months are reported in six clinical studies with 537 implants mainly restored immediately after flapless implantation procedures. Conclusion: Computer-guided template-based implant placement showed high implant survival rates ranging from 91% to 100%. However, a considerable number of technique-related perioperative complications were observed. Preclinical and clinical studies indicated a reasonable mean accuracy with relatively high maximum deviations. Future research should be directed to increase the number of clinical studies with longer observation periods and to improve the systems in terms of perioperative handling, accuracy and prosthetic complications.

Determination of the minimum alveolar concentration of isoflurane in Shetland ponies using constant current or constant voltage electrical stimulation

OBJECTIVE: To determine the minimum alveolar concentration (MAC) of isoflurane in Shetland ponies using a sequence of three different supramaximal noxious stimulations at each tested concentration of isoflurane rather than a single stimulation. STUDY DESIGN: Prospective, experimental trial. ANIMALS: Seven 4-year-old, gelding Shetland ponies. METHODS: The MAC of isoflurane was determined for each pony. Three different modes of electrical stimulation were applied consecutively (2 minute intervals): two using constant voltage (90 V) on the gingiva via needle- (CVneedle) or surface-electrodes (CVsurface) and one using constant current (CC; 40 mA) via surface electrodes applied to the skin over the digital nerve. The ability to clearly interpret the responses as positive, the latency of the evoked responses and the inter-electrode resistance were recorded for each stimulus. RESULTS: Individual isoflurane MAC (%) values ranged from 0.60 to 1.17 with a mean (+/-SD) of 0.97 (+/-0.17). The responses were more clearly interpreted with CC, but did not reach statistical significance. The CVsurface mode produced responses with a longer delay. The CVneedle mode was accompanied by variable inter-electrode resistances resulting in uncontrolled stimulus intensity. At 0.9 MAC, the third stimulation induced more positive responses than the first stimulation, independent of the mode of stimulation used. CONCLUSIONS: The MAC of isoflurane in the Shetland ponies was lower than expected with considerable variability among individuals. Constant current surface electrode stimulations were the most repeatable. A summation over the sequence of three supramaximal stimulations was observed around 0.9 MAC. CLINICAL RELEVANCE: The possibility that Shetland ponies require less isoflurane than horses needs further investigation. Constant current surface-electrode stimulations were the most repeatable. Repetitive supramaximal stimuli may have evoked movements at isoflurane concentrations that provide immobility when single supramaximal stimulation was applied.

Concentration-dependent isoflurane effects on withdrawal reflexes in pigs and the role of the stimulation paradigm

In this prospective two-phase experimental trial, 10 pigs were anaesthetized twice with isoflurane only. In the first phase, the individual minimum alveolar concentration (MAC) was determined and in the second phase the effects on withdrawal reflexes of increasing end-tidal isoflurane concentrations (from 1.6% to 2.8%) were assessed. Single, 10 and 60 repeated electrical stimulations were used to evoke withdrawal reflexes which were recorded and quantified by electromyography. Recruitment curves for reflex amplitude for increasing stimulation intensities and isoflurane concentrations were constructed. Isoflurane MAC was 1.9+/-0.3%. Reflexes evoked by repeated stimulation were suppressed at isoflurane concentrations significantly higher than those which suppressed complex movements during MAC determination (P=0.014 and P=0.006 for 10 and 60 repeated stimuli respectively). Isoflurane up to 2.8% was still not able to abolish reflex activity evoked by repeated stimulations in all pigs. Single stimulation reflexes were suppressed at significantly lower concentrations than repeated stimulation reflexes (P=0.008 and P=0.004 for 10 and 60 repeated stimuli, respectively). Reflex amplitude was significantly correlated with isoflurane concentration (P<0.001, r=-0.85) independent of the individual MAC. The findings indicate that the level at which isoflurane suppresses withdrawal reflexes is dependent on the stimulation paradigm (single vs. repeated electrical stimulation), and there is limited value in expressing reflex withdrawal suppression in terms of MAC as purposeful and reflex movements are independently affected by isoflurane in individual animals.

Small aliquot and single grain IRSL and post-IR IRSL dating of fluvial and alluvial sediments from the Pativilca valley, Peru

Infrared stimulated luminescence (IRSL) and post-IR IRSL are applied to small aliquots and single grains to determine the equivalent dose (De) of eleven alluvial and fluvial sediment samples collected in the Pativilca valley, Central Peru at ca. 10°S latitude. Small aliquot De distributions are rather symmetric and display over-dispersion values between 15 and 46%. Small aliquot g-values range between 4 and 8% per decade for the IRSL and 1 and 2% per decade for the post-IR IRSL signal. The single grain De distributions are highly over-dispersed with some of them skewed to higher doses, implying partial bleaching; this is especially true for the post-IR IRSL. Measurements of a modern analog reveal that residuals due to partial bleaching are present in both the IRSL as well as the post-IR IRSL signal. The g-values of individual grains exhibit a wide range with high individual uncertainties and might contribute significantly to the spread of the single grain De values, at least for the IRSL data. Electron Microprobe Analysis performed on single grains reveal that a varying K-content can be excluded as the origin of over-dispersion. Final ages for the different approaches are calculated using the Central Age Model and the Minimum Age Model (MAM). The samples are grouped into well-beached, potentially well-bleached and partially bleached according to the evaluation of the single grain distributions and the agreement of age estimates between methods. The application of the MAM to the single grain data resulted in consistent age estimates for both the fading corrected IRSL and the post-IR IRSL ages, and suggests that both approaches are suitable for dating these samples. Keywords

A prehistoric thoroughfare between the Ganges and the Himalayas

The greater Himalayan region, including the Tibetan plateau in the north and the Gangetic plain in the south, served as the principal prehistoric thoroughfare for the peopling of East and Southeast Asia. The descendants of ancient migrants through this region ultimately settled lands as far away as New Zealand, Madagascar and the Americas. Several of the keys to understanding the ethnogenesis of human diversity in Asia include the Father Tongue correlation, possible refugia during the Last Glacial Maximum and the hypothesis that language families may have arisen as the result of demographic bottlenecks in prehistory. Ethnolinguistically informed inferences based on Asian Y chromosomal phylogeography permit a reconstruction of episodes of ethnolinguistic prehistory which lie beyond the linguistic event horizon, i.e. beyond the time depth empirically accessible to historical linguistics. The origins of the language families which make up the hypothetical Uralo-Siberian and East Asian linguistic phyla are argued to have lain in the northeastern corner of the Indian subcontinent. Several other Asian language families are shown to be tied to the subcontinent. The Centripetal Migration model, which assumes that migrations in quest of a better life unfolded in both centrifugal and centripetal directions with respect to technologically more advanced centres of civilisation, is opposed to the Farming Language Dispersal theory, which assumes that all linguistic dispersals were driven by agricultural centrifugal migration.

Lower-tropospheric humidity: climatology, trends and the relation to the ITCZ

The tropical region is an area of maximum humidity and serves as the major humidity source of the globe. Among other phenomena, it is governed by the so-called Inter-Tropical Convergence Zone (ITCZ) which is commonly defined by converging low-level winds or enhanced precipitation. Given its importance as a humidity source, we investigate the humidity fields in the tropics in different reanalysis data sets, deduce the climatology and variability and assess the relationship to the ITCZ. Therefore, a new analysis method of the specific humidity distribution is introduced which allows detecting the location of the humidity maximum, the strength and the meridional extent. The results show that the humidity maximum in boreal summer is strongly shifted northward over the warm pool/Asia Monsoon area and the Gulf of Mexico. These shifts go along with a peak in the strength in both areas; however, the extent shrinks over the warm pool/Asia Monsoon area, whereas it is wider over the Gulf of Mexico. In winter, such connections between location, strength and extent are not found. Still, a peak in strength is again identified over the Gulf of Mexico in boreal winter. The variability of the three characteristics is dominated by inter-annual signals in both seasons. The results using ERA-interim data suggest a positive trend in the Gulf of Mexico/Atlantic region from 1979 to 2010, showing an increased northward shift in the recent years. Although the trend is only weakly confirmed by the results using MERRA reanalysis data, it is in phase with a trend in hurricane activity�a possible hint of the importance of the new method on hurricanes. Furthermore, the position of the maximum humidity coincides with one of the ITCZ in most areas. One exception is the western and central Pacific, where the area is dominated by the double ITCZ in boreal winter. Nevertheless, the new method enables us to gain more insight into the humidity distribution, its variability and the relationship to ITCZ characteristics.