Thromboembolism and bleeding in patients with atrial fibrillation and liver disease - a nationwide register-based cohort study:Thromboembolism and bleeding in liver disease

BackgroundBalancing the risk of thromboembolism and bleeding in patients with liver disease and atrial fibrillation/flutter is particularly challenging.PurposeTo examine the risks of thromboembolism and bleeding with use/non-use of oral anticoagulation (including vitamin K-antagonists and direct oral anticoagulants) in patients with liver disease and AF.MethodsDanish nationwide register-based cohort study of anticoagulant naive individuals with liver disease, incident atrial fibrillation/flutter, and a CHA2DS2-VASc-score≥1 (men) or ≥2 (women), alive 30 days after atrial fibrillation/flutter diagnosis. Thromboembolism was a composite of ischaemic stroke, transient ischaemic attack, or venous thromboembolism. Bleeding was a composite of gastrointestinal, intracerebral, or urogenital bleeding requiring hospitalisation, or epistaxis requiring emergency department visit or hospital admission. Cause-specific Cox-regression was used to estimate absolute risks and average risk ratios standardised to covariate distributions. Because of significant interactions with anticoagulants, results for thromboembolism were stratified for CHA2DS2-VASc-score, and results for bleeding were stratified for cirrhotic/non-cirrhotic liver disease.ResultsFour hundred and nine of 1,238 patients with liver disease and new atrial fibrillation/flutter initiated anticoagulants. Amongst patients with a CHA2DS2-VASc-score of 1-2 (2-3 for women), five-year thromboembolism incidence rates were low and similar in the anticoagulant (6.5%) versus no anticoagulant (5.5%) groups (average risk ratio 1.19 [95%CI, 0.22-2.16]). In patients with a CHA2DS2-VASc-score>2 (>3 for women), incidence rates were 16% versus 24% (average risk ratio 0.66 [95%CI, 0.45-0.87]). Bleeding risks appeared higher amongst patients with cirrhotic versus non-cirrhotic disease but were not significantly affected by anticoagulant status.ConclusionOral anticoagulant initiation in patients with liver disease, incident new atrial fibrillation/flutter, and a high CHA2DS2-VASc-score was associated with a reduced thromboembolism risk. Bleeding risk was not increased with anticoagulation, irrespective of the type of liver disease

A randomised comparison of deferasirox versus deferoxamine for the treatment of transfusional iron overload in sickle cell disease

Deferasirox is a once-daily, oral iron chelator developed for treating transfusional iron overload. Preclinical studies indicated that the kidney was a potential target organ of toxicity. As patients with sickle cell disease often have abnormal baseline renal function, the primary objective of this randomised, open-label, phase II trial was to evaluate the safety and tolerability of deferasirox in comparison with deferoxamine in this population. Assessment of efficacy, as measured by change in liver iron concentration (LIC) using biosusceptometry, was a secondary objective. A total of 195 adult and paediatric patients received deferasirox (n = 132) or deferoxamine (n = 63). Adverse events most commonly associated with deferasirox were mild, including transient nausea, vomiting, diarrhoea, abdominal pain and skin rash. Abnormal laboratory studies with deferasirox were occasionally associated with mild non-progressive increases in serum creatinine and reversible elevations in liver function tests. Discontinuation rates from deferasirox (11·4%) and deferoxamine (11·1%) were similar. Over 1 year, similar dose-dependent LIC reductions were observed with deferasirox and deferoxamine. Once-daily oral deferasirox has acceptable tolerability and appears to have similar efficacy to deferoxamine in reducing iron burden in transfused patients with sickle cell disease

Anthropology in the Clinic: The Problem of Cultural Competency and How to Fix It

RefereedMichael Crichton FundHarvard Medical SchoolNational Institute of Mental Health Training Grant on “Culture and Mental Health Services” (5T32MH018006-21

Light emission from a scanning tunneling microscope: Fully retarded calculation

The light emission rate from a scanning tunneling microscope (STM) scanning a noble metal surface is calculated taking retardation effects into account. As in our previous, non-retarded theory [Johansson, Monreal, and Apell, Phys. Rev. B 42, 9210 (1990)], the STM tip is modeled by a sphere, and the dielectric properties of tip and sample are described by experimentally measured dielectric functions. The calculations are based on exact diffraction theory through the vector equivalent of the Kirchoff integral. The present results are qualitatively similar to those of the non-retarded calculations. The light emission spectra have pronounced resonance peaks due to the formation of a tip-induced plasmon mode localized to the cavity between the tip and the sample. At a quantitative level, the effects of retardation are rather small as long as the sample material is Au or Cu, and the tip consists of W or Ir. However, for Ag samples, in which the resistive losses are smaller, the inclusion of retardation effects in the calculation leads to larger changes: the resonance energy decreases by 0.2-0.3 eV, and the resonance broadens. These changes improve the agreement with experiment. For a Ag sample and an Ir tip, the quantum efficiency is $\approx$ 10$^{-4}$ emitted photons in the visible frequency range per tunneling electron. A study of the energy dissipation into the tip and sample shows that in total about 1 % of the electrons undergo inelastic processes while tunneling.Comment: 16 pages, 10 figures (1 ps, 9 tex, automatically included); To appear in Phys. Rev. B (15 October 1998

The CLIF Consortium Acute Decompensation score (CLIF-C ADs) for prognosis of hospitalised cirrhotic patients without acute-on-chronic liver failure

BACKGROUND & AIMS: Cirrhotic patients with acute decompensation frequently develop acute-on-chronic liver failure (ACLF), which is associated with high mortality rates. Recently, a specific score for these patients has been developed using the CANONIC study database. The aims of this study were to develop and validate the CLIF-C AD score, a specific prognostic score for hospitalised cirrhotic patients with acute decompensation (AD), but without ACLF, and to compare this with the Child-Pugh, MELD, and MELD-Na scores. METHODS: The derivation set included 1016 CANONIC study patients without ACLF. Proportional hazards models considering liver transplantation as a competing risk were used to identify score parameters. Estimated coefficients were used as relative weights to compute the CLIF-C ADs. External validation was performed in 225 cirrhotic AD patients. CLIF-C ADs was also tested for sequential use. RESULTS: Age, serum sodium, white-cell count, creatinine and INR were selected as the best predictors of mortality. The C-index for prediction of mortality was better for CLIF-C ADs compared with Child-Pugh, MELD, and MELD-Nas at predicting 3- and 12-month mortality in the derivation, internal validation and the external dataset. CLIF-C ADs improved in its ability to predict 3-month mortality using data from days 2, 3-7, and 8-15 (C-index: 0.72, 0.75, and 0.77 respectively). CONCLUSIONS: The new CLIF-C ADs is more accurate than other liver scores in predicting prognosis in hospitalised cirrhotic patients without ACLF. CLIF-C ADs therefore may be used to identify a high-risk cohort for intensive management and a low-risk group that may be discharged early

R&D Paths of Pixel Detectors for Vertex Tracking and Radiation Imaging

This report reviews current trends in the R&D of semiconductor pixellated sensors for vertex tracking and radiation imaging. It identifies requirements of future HEP experiments at colliders, needed technological breakthroughs and highlights the relation to radiation detection and imaging applications in other fields of science.Comment: 17 pages, 2 figures, submitted to the European Strategy Preparatory Grou

Genome-wide association study identifies 30 loci associated with bipolar disorder.

Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study (GWAS) including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P < 1 × 10-4 in an additional 9,412 cases and 137,760 controls. Eight of the 19 variants that were genome-wide significant (P < 5 × 10-8) in the discovery GWAS were not genome-wide significant in the combined analysis, consistent with small effect sizes and limited power but also with genetic heterogeneity. In the combined analysis, 30 loci were genome-wide significant, including 20 newly identified loci. The significant loci contain genes encoding ion channels, neurotransmitter transporters and synaptic components. Pathway analysis revealed nine significantly enriched gene sets, including regulation of insulin secretion and endocannabinoid signaling. Bipolar I disorder is strongly genetically correlated with schizophrenia, driven by psychosis, whereas bipolar II disorder is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential biological mechanisms for bipolar disorder

Leisure, refuge and solidarity:messages in visitors’ books as microforms of travel writing

Visitors’ books not only trace developments in modern tourism, but they also reveal changes in the socio-cultural and language attitudes of travellers from all walks of life over prolonged periods of time. This article investigates messages in visitors’ books from Wales from the mid-nineteenth century up to the present and argues for their recognition as microforms of travel writing. Despite their brevity, entries in visitors’ books are a highly complex form of travel writing particularly in the inscribers’ self-fashioning of identity for future readers. The article examines how writerly choices are not only directly rooted in the discourse of travel, but also in socio-political circumstances in the individual travellers’ countries of origin and their travel destinations

Simulation of sea ice transport through Fram Strait: Natural variability and sensitivity to forcing

The interannual variability of the sea ice transport through Fram Strait is simulated with a dynamic‐thermodynamic sea ice model. Forcing with daily varying wind fields for the 7‐year period 1986–1992 causes a high variability of sea ice drift on timescales from days to years. Annual means of simulated ice transport through Pram Strait differ up to a factor of 2. Additional sensitivity studies investigate the response of sea ice transports to variations of the prescribed atmospheric and oceanic forcing. Wind speed, ocean current speed, air temperature, and precipitation rate are systematically varied over a wide range. The model predicts an almost linear relation of ice transport with wind speed and ocean current, a strong, nonlinear relation with air temperature, and a rather small sensitivity to changes in precipitation. The results show that the interannual variability of wind forcing causes considerable variations of sea ice export through Fram Strait. The fluxes of freshwater and negative latent heat associated with the sea ice transport can significantly affect the ocean circulation in the Greenland Sea and in the North Atlantic. This shows how variations of the ocean circulation are coupled to the variability of the atmosphere by the mechanism of sea ice advection. To adequately represent these important interactions in the coupled system atmosphere‐cryosphere‐ocean, both the dynamics and the thermodynamics of sea ice must be included in climate models