The status of olfactory function and the striatal dopaminergic system in drug-induced parkinsonism

Olfactory impairment has been reported in drug-induced parkinsonism (DIP), but the relationship between dopaminergic dysfunction and smell deficits in DIP patients has not been characterized. To this end, we studied 16 DIP patients and 13 patients affected by Parkinson's disease (PD) using the "Sniffin' Sticks" test and [(123)I] FP-CIT SPECT (single-photon emission computed tomography). DIP patients were divided based on normal (n = 9) and abnormal (n = 7) putamen dopamine transporter binding. Nineteen healthy age- and sex-matched subjects served as controls of smell function. Patients with DIP and pathological putamen uptake had abnormal olfactory function. In this group of patients, olfactory TDI scores (odor threshold, discrimination and identification) correlated significantly with putamen uptake values, as observed in PD patients. By contrast, DIP patients with normal putamen uptake showed odor functions-with the exception of the threshold subtest-similar to control subjects. In this group of patients, no significant correlation was observed between olfactory TDI scores and putamen uptake values. The results of our study suggest that the presence of smell deficits in DIP patients might be more associated with dopaminergic loss rather than with a drug-mediated dopamine receptor blockade. These preliminary results might have prognostic and therapeutic implications, as abnormalities in these individuals may be suggestive of an underlying PD-like neurodegenerative process.

Polymer stent coating for prevention of neointimal hyperplasia

AIMS: Restenosis has been the principal limitation of bare metal stents. Based upon the presumption that platelet and inflammatory cell recruitment initiate neointimal proliferation, we explored a novel polymer coating that reduces cell-stent interactions. The purpose of the present study was to investigate the effect of poly(L-lysine)-graft-poly(ethyleneglycol) (PLL-g-PEG) adsorbed to stent surfaces to reduce neointimal hyperplasia in the porcine restenosis model. METHODS AND RESULTS: Seven animals were instrumented each with 2 stainless steel stents (15 mm length, 2.5-3.5 mm diameter), randomly implanted in 1 major epicardial coronary artery. One stent was dip-coated with PLL-g-PEG, whereas the other stent served as the uncoated control stent. All animals were sacrificed after 6 weeks for histological examination. Neointimal hyperplasia was significantly less (-51%) in the PLL-g-PEG-coated stents (1.15 +/- 0.59 mm2) than in the uncoated control stents (2.33 +/- 1.01 mm2; p < 0.001). Conversely, lumen size was larger in the PLL-g-PEG-coated stents (2.91 +/- 1.17 mm2) than in the uncoated stents (2.04 +/- 0.64 mm2; p < 0.001). High magnification histomorphologic examination revealed no signs of inflammation or thrombus formation in either stent group. CONCLUSIONS: Polymeric steric stabilization of stents with PLL-g-PEG significantly reduces neointimal hyperplasia in the porcine restenosis model. Reduction of cell-stent interactions mediated by PLL-g-PEG appear to improve biocompatibility of stainless steel stents without evidence of adverse inflammatory or prothrombotic effects.

The influence of bedrock orientation on the landscape evolution, surface morphology and denudation (10Be) at the Niesen, Switzerland

Landscape evolution and surface morphology in mountainous settings are a function of the relative importance between sediment transport processes acting on hillslopes and in channels, modulated by climate variables. The Niesen nappe in the Swiss Penninic Prealps presents a unique setting in which opposite facing flanks host basins underlain by identical lithologies, but contrasting litho-tectonic architectures where lithologies either dip parallel to the topographic slope or in the opposite direction (i.e. dip slope and non-dip slope). The north-western facing Diemtigen flank represents such a dip slope situation and is characterized by a gentle topography, low hillslope gradients, poorly dissected channels, and it hosts large landslides. In contrast, the south-eastern facing Frutigen side can be described as non-dip slope flank with deeply incised bedrock channels, high mean hillslope gradients and high relief topography. Results from morphometric analysis reveal that noticeable differences in morphometric parameters can be related to the contrasts in the relative importance of the internal hillslope-channel system between both valley flanks. While the contrasting dip-orientations of the underlying flysch bedrock has promoted hillslope and channelized processes to contrasting extents and particularly the occurrence of large landslides on the dip slope flank, the flank averaged beryllium-10 (10Be)-derived denudation rates are very similar and range between 0.20 and 0.26 mm yr−1. In addition, our denudation rates offer no direct relationship to basin's slope, area, steepness or concavity index, but reveal a positive correlation to mean basin elevation that we interpret as having been controlled by climatically driven factors such as frost-induced processes and orographic precipitation. Our findings illustrate that while the landscape properties in this part of the northern Alpine border can mainly be related to the tectonic architecture of the underlying bedrock, the denudation rates have a strong orographic control through elevation dependent mean annual temperature and precipitation.

Bedrock bedding, landsliding and erosional budgets in the Central European Alps

We explore the controls of the litho-tectonic architecture on the erosional flux in the 370-km2 Glogn basin (European Alps). In this basin, the bedding and schistosity of the bedrock dip parallel to the topographic slope on the NW valley flank, leading to a non-dip slope situation on the opposite SE valley side. While the dip slope condition has promoted the occurrence of landslides (e.g. the c. 30-km2 deep-seated Lumnezia landslide), the opposite non-dip slope side of the valley hosts >100-m-deeply incised tributary streams. 10Be concentrations of stream sediments yield catchment-averaged denudation rates that vary between 0.27 ± 0.03 and 2.19 ± 0.37 mm a−1, while the spatially averaged denudation rate of the entire basin is 1.99 ± 0.34 mm a−1. Our 10Be-based approach reveals that the Lumnezia landslide front contributes c. 30–65% of the entire sediment budget, although it covers <5% of the Glogn basin. This suggests a primary control of the bedrock bedding on erosion rates and processes.

Tuberculosis in Cape Town: An age-structured transmission model.

BACKGROUND Tuberculosis (TB) is the leading cause of death in South Africa. The burden of disease varies by age, with peaks in TB notification rates in the HIV-negative population at ages 0-5, 20-24, and 45-49 years. There is little variation between age groups in the rates in the HIV-positive population. The drivers of this age pattern remain unknown. METHODS We developed an age-structured simulation model of Mycobacterium tuberculosis (Mtb) transmission in Cape Town, South Africa. We considered five states of TB progression: susceptible, infected (latent TB), active TB, treated TB, and treatment default. Latently infected individuals could be re-infected; a previous Mtb infection slowed progression to active disease. We further considered three states of HIV progression: HIV negative, HIV positive, on antiretroviral therapy. To parameterize the model, we analysed treatment outcomes from the Cape Town electronic TB register, social mixing patterns from a Cape Town community and used literature estimates for other parameters. To investigate the main drivers behind the age patterns, we conducted sensitivity analyses on all parameters related to the age structure. RESULTS The model replicated the age patterns in HIV-negative TB notification rates of Cape Town in 2009. Simulated TB notification rate in HIV-negative patients was 1000/100,000 person-years (pyrs) in children aged <5 years and decreased to 51/100,000 in children 5-15 years. The peak in early adulthood occurred at 25-29 years (463/100,000 pyrs). After a subsequent decline, simulated TB notification rates gradually increased from the age of 30 years. Sensitivity analyses showed that the dip after the early adult peak was due to the protective effect of latent TB and that retreatment TB was mainly responsible for the rise in TB notification rates from the age of 30 years. CONCLUSION The protective effect of a first latent infection on subsequent infections and the faster progression in previously treated patients are the key determinants of the age-structure of TB notification rates in Cape Town.

Benchmarking numerical models of brittle thrust wedges

We report quantitative results from three brittle thrust wedge experiments, comparing numerical results directly with each other and with corresponding analogue results. We first test whether the participating codes reproduce predictions from analytical critical taper theory. Eleven codes pass the stable wedge test, showing negligible internal deformation and maintaining the initial surface slope upon horizontal translation over a frictional interface. Eight codes participated in the unstable wedge test that examines the evolution of a wedge by thrust formation from a subcritical state to the critical taper geometry. The critical taper is recovered, but the models show two deformation modes characterised by either mainly forward dipping thrusts or a series of thrust pop-ups. We speculate that the two modes are caused by differences in effective basal boundary friction related to different algorithms for modelling boundary friction. The third experiment examines stacking of forward thrusts that are translated upward along a backward thrust. The results of the seven codes that run this experiment show variability in deformation style, number of thrusts, thrust dip angles and surface slope. Overall, our experiments show that numerical models run with different numerical techniques can successfully simulate laboratory brittle thrust wedge models at the cm-scale. In more detail, however, we find that it is challenging to reproduce sandbox-type setups numerically, because of frictional boundary conditions and velocity discontinuities. We recommend that future numerical-analogue comparisons use simple boundary conditions and that the numerical Earth Science community defines a plasticity test to resolve the variability in model shear zones.