Deformation and failure of the ice bridge on the Wilkins Ice Shelf, Antarctica

A narrow bridge of floating ice that connected the Wilkins Ice Shelf, Antarctica, to two confining islands eventually collapsed in early April 2009. In the month preceding the collapse, we observed deformation of the ice bridge by means of satellite imagery and from an in situ GPS station. TerraSAR-X images (acquired in stripmap mode) were used to compile a time series. The ice bridge bent most strongly in its narrowest part (westerly), while the northern end (near Charcot Island) shifted in a northeasterly direction. In the south, the ice bridge experienced compressive strain parallel to its long axis. GPS position data were acquired a little south of the narrowest part of the ice bridge from 19 January 2009. Analysis of these data showed both cyclic and monotonic components of motion. Meteorological data and re-analysis of the output of weather-prediction models indicated that easterly winds were responsible for the cyclic motion component. In particular, wind stress on the rough ice melange that occupied the area to the east exerted significant pressure on the ice bridge. The collapse of the ice bridge began with crack formation in the southern section parallel to the long axis of the ice bridge and led to shattering of the southern part. Ultimately, the narrowest part, only 900 m wide, ruptured. The formation of many small icebergs released energy of >125 × 106 J

Receptor activation using multi-biomarker pharmacokinetic/pharmacodynamic modelling

receptor activation was evaluated using quinpirole as a paradigm compound. ), as well as plasma concentrations of 13 hormones and neuropeptides, were measured. Experiments were performed at day 1 and repeated after 7-day s.c. drug administration. PK/PD modelling was applied to identify the in vivo concentration-effect relations and neuroendocrine dynamics. receptor expression levels on the pituitary hormone-releasing cells predicted the concentration-effect relationship differences. Baseline levels (ACTH, prolactin, TSH), hormone release (ACTH) and potency (TSH) changed with treatment duration. agonists in clinical practice. Further development towards quantitative systems pharmacology models will eventually facilitate mechanistic drug development. BACKGROUND AND PURPOSE EXPERIMENTAL APPROACH KEY RESULTS CONCLUSIONS AND IMPLICATION

Reproducibility of the Pleth Variability Index in premature infants

The aim was to assess the reproducibility of the Pleth Variability Index (PVI), developed for non-invasive monitoring of peripheral perfusion, in preterm neonates below 32 weeks of gestational age. Three PVI measurements were consecutively performed in stable, comfortable preterm neonates in the first 48 h of life. On each occasion, pulse oximeter sensors were attached to two different limbs for 5 min. Reproducibility was assessed with the intra-class correlation coefficient (ICC) and Bland–Altman analysis. A total of 25 preterm neonates were included. Inter-limb comparison showed fair to moderate ICC’s with 95%-confidence intervals (95%-CI). Left hand–right hand ICC = 0.498, 95%-CI (0.119–0.753); right foot–right hand ICC = 0.314 (−0.088–0.644); right foot–left foot ICC = 0.315 (−0.089–0.628). Intra-limb comparison showed fair to moderate ICC for right foot–right foot ICC = 0.380 (−0.014–0.677); and good ICC for right hand–right hand ICC = 0.646 (0.194–0.852). Bland–Altman plots showed moderate reproducibility of measurements between different limbs and of the same limb in consecutive time periods, with large biases and wide limits of agreement. The findings from this study indicate that PVI measurement is poorly reproducible when measured on different limbs and on the same limb in stable and comfortable preterm neonates

Fingerprints of CNS drug effects: a plasma neuroendocrine reflection of D2 receptor activation using multi-biomarker pharmacokinetic/pharmacodynamic modelling

Background and PurposeBecause biological systems behave as networks, multi‐biomarker approaches increasingly replace single biomarker approaches in drug development. To improve the mechanistic insights into CNS drug effects, a plasma neuroendocrine fingerprint was identified using multi‐biomarker pharmacokinetic/pharmacodynamic (PK/PD) modelling. Short‐ and long‐term D2 receptor activation was evaluated using quinpirole as a paradigm compound.Experimental ApproachRats received 0, 0.17 or 0.86 mg·kg−1 of the D2 agonist quinpirole i.v. Quinpirole concentrations in plasma and brain extracellular fluid (brainECF), as well as plasma concentrations of 13 hormones and neuropeptides, were measured. Experiments were performed at day 1 and repeated after 7‐day s.c. drug administration. PK/PD modelling was applied to identify the in vivo concentration–effect relations and neuroendocrine dynamics.Key ResultsThe quinpirole pharmacokinetics were adequately described by a two‐compartment model with an unbound brainECF‐to‐plasma concentration ratio of 5. The release of adenocorticotropic hormone (ACTH), growth hormone, prolactin and thyroid‐stimulating hormone (TSH) from the pituitary was influenced. Except for ACTH, D2 receptor expression levels on the pituitary hormone‐releasing cells predicted the concentration–effect relationship differences. Baseline levels (ACTH, prolactin, TSH), hormone release (ACTH) and potency (TSH) changed with treatment duration.Conclusions and ImplicationsThe integrated multi‐biomarker PK/PD approach revealed a fingerprint reflecting D2 receptor activation. This forms the conceptual basis for in vivo evaluation of on‐ and off‐target CNS drug effects. The effect of treatment duration is highly relevant given the long‐term use of D2 agonists in clinical practice. Further development towards quantitative systems pharmacology models will eventually facilitate mechanistic drug development.Pharmacolog

Deceleration and trapping of heavy diatomic molecules using a ring-decelerator

We present an analysis of the deceleration and trapping of heavy diatomic molecules in low-field seeking states by a moving electric potential. This moving potential is created by a 'ring-decelerator', which consists of a series of ring-shaped electrodes to which oscillating high voltages are applied. Particle trajectory simulations have been used to analyze the deceleration and trapping efficiency for a group of molecules that is of special interest for precision measurements of fundamental discrete symmetries. For the typical case of the SrF molecule in the (N,M) = (2, 0) state, the ring-decelerator is shown to outperform traditional and alternate-gradient Stark decelerators by at least an order of magnitude. If further cooled by a stage of laser cooling, the decelerated molecules allow for a sensitivity gain in a parity violation measurement, compared to a cryogenic molecular beam experiment, of almost two orders of magnitude

Early systemic microvascular damage in pigs with atherogenic diabetes mellitus coincides with renal angiopoietin dysbalance

Background: Diabetes mellitus (DM) is associated with a range of microvascular complications including diabetic nephropathy (DN). Microvascular abnormalities in the kidneys are common histopathologic findings in DN, which represent one manifestation of ongoing systemic microvascular damage. Recently, sidestream dark-field (SDF) imaging has emerged as a noninvasive tool that enables one to visualize the microcirculation. In this study, we investigated whether changes in the systemic microvasculature induced by DM and an atherogenic diet correlated spatiotemporally with renal damage. Methods: Atherosclerotic lesion development was triggered in streptozotocin-induced DM pigs (140 mg/kg body weight) by administering an atherogenic diet for approximately 11 months. Fifteen months following induction of DM, microvascular morphology was visualized in control pigs (n = 7), non-diabetic pigs fed an atherogenic diet (ATH, n = 5), and DM pigs fed an atherogenic diet (DM+ATH, n = 5) using SDF imaging of oral mucosal tissue. Subsequently, kidneys were harvested from anethesized pigs and the expression levels of well-established markers for microvascular integrity, such as Angiopoietin-1 (Angpt1) and Angiopoietin-2 (Angpt2) were determined immunohistochemically, while endothelial cell (EC) abundance was determined by immunostaining for von Willebrand factor (vWF). Results: Our study revealed an increase in the capillary tortuosity index in DM+ATH pigs (2.31±0.17) as compared to the control groups (Controls 0.89±0.08 and ATH 1.55±0.11; p<0.05). Kidney biopsies showed marked glomerular lesions consisting of mesangial expansion and podocyte lesions. Furthermore, we observed a disturbed Angpt2/ Angpt1balance in the cortex of the kidney, as evidenced by increased expression of Angpt2 in DM+ATH pigs as compared to Control pigs (p<0.05). Conclusion: In the setting of DM, atherogenesis leads to the augmentation of mucosal capillary tortuosity, indicative of systemic microvascular damage. Concomitantly, a dysbalance in renal angiopoietins was correlated with the development of diabetic nephropathy. As such, our studies strongly suggest that defects in the systemic microvasculature mirror the accumulation of microvascular damage in the kidney

A multi-disciplinary perspective on climate model evaluation for Antarctica

A workshop was organized by Antarctic Climate 21 (AntClim21), with the topic 'evaluation of climate models' representation of Antarctic climate from the perspective of long-term twenty-first-century climate change.' The suggested approach for evaluating whether climate models over- or underestimate the effects of ozone depletion is to diagnose simulated historical trends in lower-stratospheric temperature and compare these to observational estimates. With regard to more regional changes over Antarctica, such as West Antarctic warming, the simulation of teleconnection patterns to the tropical Pacific was highlighted. To improve the evaluation of low-frequency variability and trends in climate models, the use and development of approaches to emulate ice-core proxies in models was recommended. It is recommended that effort be put into improving datasets of ice thickness, motion, and composition to allow for a more complete evaluation of sea ice in climate models. One process that was highlighted in particular is the representation of Antarctic clouds and resulting precipitation. It is recommended that increased effort be put into observations of clouds over Antarctica, such as the use of instruments that can detect cloud-base height or the use of remote sensing resources

The modelled surface mass balance of the Antarctic Peninsula at 5.5 km horizontal resolution.

This study presents a high-resolution (similar to 5.5 km) estimate of surface mass balance (SMB) over the period 1979-2014 for the Antarctic Peninsula (AP), generated by the regional atmospheric climate model RACMO2.3 and a firn densification model (FDM). RACMO2.3 is used to force the FDM, which calculates processes in the snowpack, such as meltwater percolation, refreezing and runoff. We evaluate model output with 132 in situ SMB observations and discharge rates from six glacier drainage basins, and find that the model realistically simulates the strong spatial variability in precipitation, but that significant biases remain as a result of the highly complex topography of the AP. It is also clear that the observations significantly underrepresent the high-accumulation regimes, complicating a full model evaluation. The SMB map reveals large accumulation gradients, with precipitation values above 3000 mm we yr(-1) in the western AP (WAP) and below 500 mm we yr(-1) in the eastern AP (EAP), not resolved by coarser data sets such as ERA-Interim. The average AP ice-sheet-integrated SMB, including ice shelves (an area of 4.1 x 10(5) km(2)), is estimated at 351 Gt yr(-1) with an interannual variability of 58 Gt yr(-1), which is dominated by precipitation (PR) (365 +/- 57 Gt yr(-1)). The WAP (2.4 x 10(5) km(2)) SMB (276 +/- 47 Gt yr(-1)), where PR is large (276 +/- 47 Gt yr(-1)), dominates over the EAP (1.7 x 10(5) km(2)) SMB (75 +/- 11 Gt yr(-1)) and PR (84 +/- 11 Gt yr(-1)). Total sublimation is 11 +/- 2 Gt yr(-1) and meltwater runoff into the ocean is 4 +/- 4 Gt yr(-1). There are no significant trends in any of the modelled AP SMB components, except for snowmelt that shows a significant decrease over the last 36 years (-0.36 Gt yr(-2))