Prevention of Catheter-Related Bacteremia with a Daily Ethanol Lock in Patients with Tunnelled Catheters: A Randomized, Placebo-Controlled Trial

Background: Catheter-related bloodstream infection (CRBSI) results in significant attributable morbidity and mortality. In this randomized, double-blind, placebo-controlled trial, we studied the efficacy and safety of a daily ethanol lock for the prevention of CRBSI in patients with a tunnelled central venous catheter (CVC). Methodology: From 2005 through 2008, each lumen of the CVC of adult hematology patients was locked for 15 minutes per day with either 70%-ethanol or placebo, where after the lock solution was flushed through. As a primary endpoint, the incidence rates of endoluminal CRBSI were compared. Principal Findings: The intent-to-treat analysis was based on 376 patients, accounting for 448 CVCs and 27,745 catheter days. For ethanol locks, the incidence of endoluminal CRBSI per 1000 CVC-days was 0.70 (95%-CI, 0.4-1.3), compared to 1.19 (95% confidence interval, 0.7-1.9) for placebo (incidence rate-ratio, 0.59; 95% confidence interval, 0.27-1.30; P = .19). For endoluminal CRBSI according to the strictest definition (positive hub culture and identical bacterial strain in blood), a 3.6-fold, non-significant, reduction was observed for patients receiving ethanol (2 of 226 versus 7 of 222; P = .103). No lifethreatening adverse events were observed. More patients receiving ethanol discontinued lock-therapy (11 of 226 versus 1 of 222; P = .006) or continued with decreased lock-frequency (10 of 226 versus 0 of 222; P = .002), due to non-severe adverse events. Conclusions: In this study, the reduction in the incidence of endoluminal CRBSI using preventive ethanol locks was nonsignificant, although the low incidence of endoluminal CRBSI precludes definite conclusions. Therefore, the lack of statistical significance may partially reflect a lack of power. Significantly more patients treated with ethanol locks discontinued their prophylactic treatment due to adverse effects, which were non-severe but reasonably ethanol related. Additional studies should be performed in populations with higher incidence of (endoluminal) CRBSI. Alternative sources of bacteremia, like exoluminal CRBSI or microbial translocation during chemotherapy-induced mucositis may have been more important in our patients. Trial Registration: ClinicalTrials.gov NCT00122642

Miocene Antarctic Ice Sheet area adapts significantly faster than volume to CO2-induced climate change

The strongly varying benthic δ18O levels of the early and mid-Miocene (23 to 14 Myr ago) are primarily caused by a combination of changes in Antarctic Ice Sheet (AIS) volume and deep-ocean temperatures. These factors are coupled since AIS changes affect deep-ocean temperatures. It has recently been argued that this is due to changes in ice sheet area rather than volume because area changes affect the surface albedo. This finding would be important when the transient AIS grows relatively faster in extent than in thickness, which we test here. We analyse simulations of Miocene AIS variability carried out using the three-dimensional ice sheet model IMAU-ICE forced by warm (high CO2, no ice) and cold (low CO2, large East AIS) climate snapshots. These simulations comprise equilibrium and idealized quasiorbital transient runs with strongly varying CO2 levels (280 to 840 ppm). Our simulations show a limited direct effect of East AIS changes on Miocene orbital-timescale benthic δ18O variability because of the slow build-up of volume. However, we find that relative to the equilibrium ice sheet size, the AIS area adapts significantly faster and more strongly than volume to the applied forcing variability. Consequently, during certain intervals the ice sheet is receding at the margins, while ice is still building up in the interior. That means the AIS does not adapt to a changing equilibrium size at the same rate or with the same sign everywhere. Our results indicate that the Miocene Antarctic Ice Sheet affects deep-ocean temperatures more than its volume suggests

F18 fluorodeoxyglucose uptake in progressive transformation of germinal centres

FDG-PET/CT is a widely established imaging modality for staging, restaging and monitoring therapy response in lymphoma patients. Progressive transformation of germinal centres (PTGC) is a benign condition presenting characteristically as asymptomatic lymphadenopathy. This paper presents a case of a 53-year-old man with a history of Hodgkin’s disease (HD) whose F18 FDG-PET/CT scan showed high uptake in left axillary lymph nodes (SUV 3.8). A subsequent, left axillary lymph node biopsy revealed PTGC. PTGC can present as a false positive finding on FDG-PET/CT in lymphoma patients and biopsy should be done in HD patients in clinical remission but have a positive FDG-PET/CT scan

A State-Dependent Quantification of Climate Sensitivity Based on Paleodata of the Last 2.1 Million Years

The evidence from both data and models indicates that specific equilibrium climate sensitivity S[X]—the global annual mean surface temperature change (ΔTg) as a response to a change in radiative forcing X (ΔR[X])—is state dependent. Such a state dependency implies that the best fit in the scatterplot of ΔTg versus ΔR[X] is not a linear regression but can be some nonlinear or even nonsmooth function. While for the conventional linear case the slope (gradient) of the regression is correctly interpreted as the specific equilibrium climate sensitivity S[X], the interpretation is not straightforward in the nonlinear case. We here explain how such a state-dependent scatterplot needs to be interpreted and provide a theoretical understanding—or generalization—how to quantify S[X] in the nonlinear case. Finally, from data covering the last 2.1 Myr we show that—due to state dependency—the specific equilibrium climate sensitivity which considers radiative forcing of CO2 and land ice sheet (LI) albedo, $S_{[CO_2,LI]}$, is larger during interglacial states than during glacial conditions by more than a factor 2

Benchmarking the vertically integrated ice-sheet model IMAU-ICE (version 2.0)

Ice-dynamical processes constitute a large uncertainty in future projections of sea-level rise caused by anthropogenic climate change. Improving our understanding of these processes requires ice-sheet models that perform well at simulating both past and future ice-sheet evolution. Here, we present version 2.0 of the ice-sheet model IMAU-ICE, which uses the depth-integrated viscosity approximation (DIVA) to solve the stress balance. We evaluate its performance in a range of benchmark experiments, including simple analytical solutions and both schematic and realistic model intercomparison exercises. IMAU-ICE has adopted recent developments in the numerical treatment of englacial stress and sub-shelf melt near the grounding line, which result in good performance in experiments concerning grounding-line migration (MISMIP, MISMIP+) and buttressing (ABUMIP). This makes it a model that is robust, versatile, and user-friendly, which will provide a firm basis for (palaeo-)glaciological research in the coming years

Modelling feedbacks between the Northern Hemisphere ice sheets and climate during the last glacial cycle

During the last glacial cycle (LGC), ice sheets covered large parts of Eurasia and North America, which resulted in ∼120 m of sea level change. Ice sheet-climate interactions have considerable influence on temperature and precipitation patterns and therefore need to be included when simulating this time period. Ideally, ice sheet-climate interactions are simulated by a high-resolution Earth system model. While these models are capable of simulating climates at a certain point in time, such as the pre-industrial (PI) or the Last Glacial Maximum (LGM; 21 000 years ago), a full transient glacial cycle is currently computationally unfeasible as it requires a too-large amount of computation time. Nevertheless, ice sheet models require forcing that captures the gradual change in climate over time to calculate the accumulation and melt of ice and its effect on ice sheet extent and volume changes. Here we simulate the LGC using an ice sheet model forced by LGM and PI climates. The gradual change in climate is modelled by transiently interpolating between pre-calculated results from a climate model for the LGM and the PI. To assess the influence of ice sheet-climate interactions, we use two different interpolation methods: the climate matrix method, which includes a temperature-albedo and precipitation-topography feedback, and the glacial index method, which does not. To investigate the sensitivity of the results to the prescribed climate forcing, we use the output of several models that are part of the Paleoclimate Modelling Intercomparison Project Phase III (PMIP3). In these simulations, ice volume is prescribed, and the climate is reconstructed with a general circulation model (GCM). Here we test those models by using their climate to drive an ice sheet model over the LGC. We find that the ice volume differences caused by the climate forcing exceed the differences caused by the interpolation method. Some GCMs produced unrealistic LGM volumes, and only four resulted in reasonable ice sheets, with LGM Northern Hemisphere sea level contribution ranging between 74-113 m with respect to the present day. The glacial index and climate matrix methods result in similar ice volumes at the LGM but yield a different ice evolution with different ice domes during the inception phase of the glacial cycle and different sea level rates during the deglaciation phase. The temperature-albedo feedback is the main cause of differences between the glacial index and climate matrix methods

Strategies for fitting nonlinear ecological models in R, AD Model Builder, and BUGS

Summary: 1. Ecologists often use nonlinear fitting techniques to estimate the parameters of complex ecological models, with attendant frustration. This paper compares three open-source model fitting tools and discusses general strategies for defining and fitting models. 2. R is convenient and (relatively) easy to learn, AD Model Builder is fast and robust but comes with a steep learning curve, while BUGS provides the greatest flexibility at the price of speed. 3. Our model-fitting suggestions range from general cultural advice (where possible, use the tools and models that are most common in your subfield) to specific suggestions about how to change the mathematical description of models to make them more amenable to parameter estimation. 4. A companion web site (https://groups.nceas.ucsb.edu/nonlinear-modeling/projects) presents detailed examples of application of the three tools to a variety of typical ecological estimation problems; each example links both to a detailed project report and to full source code and data

Sea ice breakup and marine melt of a retreating tidewater outlet glacier in northeast Greenland (81°N)

Rising temperatures in the Arctic cause accelerated mass loss from the Greenland Ice Sheet and reduced sea ice cover. Tidewater outlet glaciers represent direct connections between glaciers and the ocean where melt rates at the ice-ocean interface are influenced by ocean temperature and circulation. However, few measurements exist near outlet glaciers from the northern coast towards the Arctic Ocean that has remained nearly permanently ice covered. Here we present hydrographic measurements along the terminus of a major retreating tidewater outlet glacier from Flade Isblink Ice Cap. We show that the region is characterized by a relatively large change of the seasonal freshwater content, corresponding to ~2 m of freshwater, and that solar heating during the short open water period results in surface layer temperatures above 1 °C. Observations of temperature and salinity supported that the outlet glacier is a floating ice shelf with near-glacial subsurface temperatures at the freezing point. Melting from the surface layer significantly influenced the ice foot morphology of the glacier terminus. Hence, melting of the tidewater outlet glacier was found to be critically dependent on the retreat of sea ice adjacent to the terminus and the duration of open water

Angiogenesis extent and macrophage density increase simultaneously with pathological progression in B-cell non-Hodgkin's lymphomas

Node biopsies of 30 benign lymphadenopathies and 71 B-cell non-Hodgkin's lymphomas (B-NHLs) were investigated for microvessel and macrophage counts using immunohistochemistry and morphometric analysis. Both counts were significantly higher in B-NHL. Moreover, when these were grouped into low-grade and high-grade lymphomas, according to the Kiel classification and Working Formulation (WF), statistically significant higher counts were found in the high-grade tumours. Immunohistochemistry and electron microscopy revealed a close spatial association between microvessels and macrophages. Overall, the results suggest that, in analogy to what has already been shown in solid tumours, angiogenesis occurring in B-NHLs increases with tumour progression, and that macrophages promote the induction of angiogenesis via the release of their angiogenic factors. © 1999 Cancer Research Campaig