Estimating loss to follow-up in HIV-infected patients on antiretroviral therapy: the effect of the competing risk of death in Zambia and Switzerland

Background Loss to follow-up (LTFU) is common in antiretroviral therapy (ART) programmes. Mortality is a competing risk (CR) for LTFU; however, it is often overlooked in cohort analyses. We examined how the CR of death affected LTFU estimates in Zambia and Switzerland. Methods and Findings HIV-infected patients aged ≥18 years who started ART 2004–2008 in observational cohorts in Zambia and Switzerland were included. We compared standard Kaplan-Meier curves with CR cumulative incidence. We calculated hazard ratios for LTFU across CD4 cell count strata using cause-specific Cox models, or Fine and Gray subdistribution models, adjusting for age, gender, body mass index and clinical stage. 89,339 patients from Zambia and 1,860 patients from Switzerland were included. 12,237 patients (13.7%) in Zambia and 129 patients (6.9%) in Switzerland were LTFU and 8,498 (9.5%) and 29 patients (1.6%), respectively, died. In Zambia, the probability of LTFU was overestimated in Kaplan-Meier curves: estimates at 3.5 years were 29.3% for patients starting ART with CD4 cells <100 cells/µl and 15.4% among patients starting with ≥350 cells/µL. The estimates from CR cumulative incidence were 22.9% and 13.6%, respectively. Little difference was found between naïve and CR analyses in Switzerland since only few patients died. The results from Cox and Fine and Gray models were similar: in Zambia the risk of loss to follow-up and death increased with decreasing CD4 counts at the start of ART, whereas in Switzerland there was a trend in the opposite direction, with patients with higher CD4 cell counts more likely to be lost to follow-up. Conclusions In ART programmes in low-income settings the competing risk of death can substantially bias standard analyses of LTFU. The CD4 cell count and other prognostic factors may be differentially associated with LTFU in low-income and high-income settings.

Impact of age and comorbidities on long-term survival of patients with high-risk prostate cancer treated with radical prostatectomy: a multi-institutional competing-risks analysis

Survival after surgical treatment using competing-risk analysis has been previously examined in patients with prostate cancer (PCa). However, the combined effect of age and comorbidities has not been assessed in patients with high-risk PCa who might have heterogeneous rates of competing mortality despite the presence of aggressive disease.

Water versus ice: The competing roles of modern climate and Pleistocene glacial erosion in the Central Alps of Switzerland

Recent studies have identified relationships between landscape form, erosion and climate in regions of landscape rejuvenation, associated with increased denudation. Most of these landscapes are located in non-glaciated mountain ranges and are characterized by transient geomorphic features. The landscapes of the Swiss Alps are likewise in a transient geomorphic state as seen by multiple knickzones. In this mountain belt, the transient state has been related to erosional effects during the Late Glacial Maximum (LGM). Here, we focus on the catchment scale and categorize hillslopes based on erosional mechanisms, landscape form and landcover. We then explore relationships of these variables to precipitation and extent of LGM glaciers to disentangle modern versus palaeo controls on the modern shape of the Alpine landscape. We find that in grasslands, the downslope flux of material mainly involves unconsolidated material through hillslope creep, testifying a transport-limited erosional regime. Alternatively, strength-limited hillslopes, where erosion is driven by bedrock failure, are covered by forests and/or expose bedrock, and they display oversteepened hillslopes and channels. There, hillslope gradients and relief are more closely correlated with LGM ice occurrence than with precipitation or the erodibility of the underlying bedrock. We relate the spatial occurrence of the transport- and strength-limited process domains to the erosive effects of LGM glaciers. In particular, strength-limited, rock dominated basins are situated above the equilibrium line altitude (ELA) of the LGM, reflecting the ability of glaciers to scour the landscape beyond threshold slope conditions. In contrast, transport-limited, soil-mantled landscapes are common below the ELA. Hillslopes covered by forests occupy the elevations around the ELA and are constrained by the tree line. We conclude that the current erosional forces at work in the Central Alps are still responding to LGM glaciation, and that the modern climate has not yet impacted on the modern landscape.

Legal Implications of the Use of Export Taxes in Addressing Carbon Leakage: Competing Border Adjustment Measures

The prevailing uncertainties about the future of the post-Kyoto international legal framework for climate mitigation and adaptation increase the likelihood of unilateral trade interventions that aim to address climate policy concerns, as exemplified by the controversial European Union initiative to include the aviation industry in its emissions trading system. The emerging literature suggests that border carbon adjustment (BCA) measures imposed by importing countries would lead to substantial legal complications in relation to World Trade Organization law and hence to possible trade disputes. Lack of legal clarity on BCAs is exacerbated by potential counter or pre-emptive export restrictions that exporting countries might impose on carbon-intensive products. In this context, this paper investigates the interface between legal and welfare implications of competing unilateral BCA measures. It argues that carbon export taxes will be an inevitable part of the future climate change regime in the absence of a multilateral agreement. It also describes the channels through which competing BCAs may lead to trade conflicts and political complications as a result of their distributional and welfare impacts at the domestic and global levels.

Competition and cooperation between antiferrodistortive and ferroelectric instabilities in the model perovskite SrTiO₃

We use density functional theory to explore the interplay between octahedral rotations and ferroelectricity in the model compound SrTiO3. We find that over the experimentally relevant range octahedral rotations suppress ferroelectricity as is generally assumed in the literature. Somewhat surprisingly, we observe that at larger angles the previously weakened ferroelectric instability strengthens significantly. By analyzing geometry changes, energetics, force constants and charges, we explain the mechanisms behind this transition from competition to cooperation with increasing octahedral rotation angle.

Kelvin-Helmholtz instabilities at the magnetic cavity boundary of comet 67P/Churyumov-Gerasimenko

We investigate the plasma environment of comet 67P/Churyumov-Gerasimenko, the target of the European Space Agency's Rosetta mission. Rosetta will rendezvous with the comet in 2014 at almost 3.5 AU and follow it all the way to and past perihelion at 1.3 AU. During its journey towards the inner solar system the comet's environment will significantly change. The interaction of the solar wind with a well developed neutral coma leads to the formation of an upstream bow shock and, closer to the comet, the inner shock separating the solar wind, with cometary pick-up ions mass-loaded, from the inner cometary ions which are dragged outward through abundant collisions and charge exchange with the expanding neutral gas. As a consequence the interplanetary magnetic field is prevented from penetrating the innermost region of the comet, the so-called magnetic cavity. We use our magnetohydrodynamics model BATSRUS (Block-Adaptive-Tree-Solarwind-Roe-Upwind-Scheme) to simulate the solar wind - comet interaction. The model includes photoionization, ion-electron recombination, and charge exchange. Under certain conditions our model predicts an unstable plasma flow at the inner shock. We show that the plasma shear flow around the magnetic cavity can lead to Kelvin-Helmholtz instabilities. We investigate the onset of this phenomenon with change of heliocentric distance and furthermore show that a previously stable magnetic cavity boundary can become unstable when the neutral gas is predominately released from the dayside of the comet.

On the initiation of boudinage and folding instabilities in layered elasto-visco-plastic solids - Insights from natural microstructures and numerical simulations

The present understanding of the initiation of boudinage and folding structures is based on viscosity contrasts and stress exponents, considering an intrinsically unstable state of the layer. The criterion of localization is believed to be prescribed by geometry-material interactions, which are often encountered in natural structures. An alternative localization phenomenon has been established for ductile materials, in which instability emerges for critical material parameters and loading rates from homogeneous conditions. In this thesis, conditions are sought under which this type of instability prevails and whether localization in geological materials necessarily requires a trigger by geometric imperfections. The relevance of critical deformation conditions, material parameters and the spatial configuration of instabilities are discussed in a geological context. In order to analyze boudinage geometries, a numerical eigenmode analysis is introduced. This method allows determining natural frequencies and wavelengths of a structure and inducing perturbations on these frequencies. In the subsequent coupled thermo-mechanical simulations, using a grain size evolution and end-member flow laws, localization emerges when material softening through grain size sensitive viscous creep sets in. Pinch-and-swell structures evolve along slip lines through a positive feedback between the matrix response and material bifurcations inside the layer, independent from the mesh-discretization length scale. Since boudinage and folding are considered to express the same general instability, both structures should arise independently of the sign of the loading conditions and for identical material parameters. To this end, the link between material to energy instabilities is approached by means of bifurcation analyses of the field equations and finite element simulations of the coupled system of equations. Boudinage and folding structures develop at the same critical energy threshold, where dissipative work by temperature-sensitive creep overcomes the diffusive capacity of the layer. This finding provides basis for a unified theory for strain localization in layered ductile materials. The numerical simulations are compared to natural pinch-and-swell microstructures, tracing the adaption of grain sizes, textures and creep mechanisms in calcite veins. The switch from dislocation to diffusion creep relates to strain-rate weakening, which is induced by dissipated heat from grain size reduction, and marks the onset of continuous necking. The time-dependent sequence uncovers multiple steady states at different time intervals. Microstructurally and mechanically stable conditions are finally expressed in the pinch-and-swell end members. The major outcome of this study is that boudinage and folding can be described as the same coupled energy-mechanical bifurcation, or as one critical energy attractor. This finding allows the derivation of critical deformation conditions and fundamental material parameters directly from localized structures in the field.