Hormonal replacement therapy, prothrombotic mutations and the risk of venous thrombosis

Hormone replacement therapy (HRT) increases the risk of venous thrombosis. We investigated whether this risk is affected by carriership of hereditary prothrombotic abnormalities. Therefore, we determined the two most common prothrombotic mutations, factor V Leiden and prothrombin 20210A in women who participated in a case-control study on venous thrombosis. Relative risks were expressed as odds ratios (OR) with 95% confidence intervals (CI95). Among 7 7 women aged 45-64 years with a first venous thrombosis, 51% were receiving HRT at the time of thrombosis, compared with 24% of control women (OR = 3.3, CI95 1.8-5.8). Among the patients, 23% had a prothrombotic defect, versus 7% among the control women (OR = 3.8, CI95 1.7- 8.5). Women who had factor V Leiden and used HRT had a 15-fold increased risk (OR = 15.5, CI95 3.1-77), which exceeded the expected joint odds ratio of 6.1 (under an additive model). We conclude that the thrombotic risk of HRT may particularly affect women with prothrombotic mutations. Efforts to avoid HRT in women with increased risk of thrombosis are advisable

Late gadolinium enhancement and subclinical cardiac dysfunction on cardiac MRI in asymptomatic HIV-positive men

Background: HIV is associated with an increased risk of cardiovascular disease (CVD) and related clinical events. While traditional risk factors play an important role in the pathology of cardiovascular disease, HIV infection and its sequelae of immune activation and inflammation may have significant effects on the myocardium before becoming clinically evident. Cardiac MRI (CMR) can be used to detect the pattern of these subclinical changes. This will lead to a better understanding of risk factors contributing to cardiovascular disease prior to it becoming clinically significant in HIV-positive patients. Methods: Prospective cohort study of 127 asymptomatic HIV-positive men on ART compared to 35 matched controls. Baseline demographics, HIV parameters, 12-lead ECG, routine biochemistry, and traditional cardiovascular risk factors were recorded. Images were acquired on a 3T Achieva Philips MRI scanner with 5 channel phase array cardiac coil and weight-based IV gadolinium was given at 0.15 mmol/kg dose with post-contrast inversion recovery imaging after 10 minutes. Results: 6/127 (4.7%) of asymptomatic HIV-positive men had late gadolinium enhancement (LGE) on MRI verses 1/35 (2.9%) in the control group. In 3/6 (50%) of cases this was in a classical infarction pattern with subendocardial involvement. 3/6 (50%) were consistent with prior myocarditis. There was no significant difference in mean LVEF (66.93% vs 65.18%), LVMI (60.05g/m2 vs 55.94g/m2) or posterolateral wall thickness (8.28 mm and 8.16 mm) between cases and controls respectively. There was significantly more diastolic dysfunction, E:A ratio < 1, found in the HIV-positive group, 18% vs 7% of controls (p = 0.037). Framingham risk did not predict either of these outcomes. Conclusions: There is an increased incidence of LGE detected on CMR in this asymptomatic HIV-positive cohort. Two distinct pathological processes were identifed as causing these changes, myocardial infarction and myocarditis. These findings were independent of traditional cardiac risk factors, duration of HIV infection and ART therapy. Sub clinical cardiac dysfunction may be underreported in other cardiac evaluation studies. The true impact of other potential risk factors may also be underestimated, highlighting the need for the development of more complex prediction models

The Highly Miniaturised Radiation Monitor

We present the design and preliminary calibration results of a novel highly miniaturised particle radiation monitor (HMRM) for spacecraft use. The HMRM device comprises a telescopic configuration of active pixel sensors enclosed in a titanium shield, with an estimated total mass of 52 g and volume of 15 cm$^3$. The monitor is intended to provide real-time dosimetry and identification of energetic charged particles in fluxes of up to 10$^8$ cm$^{-2}$ s$^{-1}$ (omnidirectional). Achieving this capability with such a small instrument could open new prospects for radiation detection in space.Comment: 17 pages, 15 figure

Thermocurrents and their Role in high Q Cavity Performance

Over the past years it became evident that the quality factor of a superconducting cavity is not only determined by its surface preparation procedure, but is also influenced by the way the cavity is cooled down. Moreover, different data sets exists, some of them indicate that a slow cool-down through the critical temperature is favourable while other data states the exact opposite. Even so there where speculations and some models about the role of thermo-currents and flux-pinning, the difference in behaviour remained a mystery. In this paper we will for the first time present a consistent theoretical model which we confirmed by data that describes the role of thermo-currents, driven by temperature gradients and material transitions. We will clearly show how they impact the quality factor of a cavity, discuss our findings, relate it to findings at other labs and develop mitigation strategies which especially addresses the issue of achieving high quality factors of so-called nitrogen doped cavities in horizontal test

Laboratory Characterization and Astrophysical Detection of Vibrationally Excited States of Vinyl Cyanide in Orion-KL

New laboratory data of CH$_2$CHCN (vinyl cyanide) in its ground and vibrationally excited states at the microwave to THz domain allow searching for these excited state transitions in the Orion-KL line survey. Frequency-modulated spectrometers combined into a single broadband 50-1900 GHz spectrum provided measurements of CH$_2$CHCN covering a spectral range of 18-1893 GHz, whose assignments was confirmed by Stark modulation spectra in the 18-40 GHz region and by ab-initio anharmonic force field calculations. For analyzing the emission lines of CH$_2$CHCN species detected in Orion-KL we used the excitation and radiative transfer code (MADEX) at LTE conditions. The rotational transitions of the ground state of this molecule emerge from four cloud components of hot core nature which trace the physical and chemical conditions of high mass star forming regions in the Orion-KL Nebula. The total column density of CH$_2$CHCN in the ground state is (3.0$\pm$0.9)x10$^{15}$ cm$^{-2}$. We report on the first interstellar detection of transitions in the v10=1/(v11=1,v15=1) dyad in space, and in the v11=2 and v11=3 states in Orion-KL. The lowest energy vibrationally excited states of vinyl cyanide such as v11=1 (at 328.5 K), v15=1 (at 478.6 K), v11=2 (at 657.8 K), the v10=1/(v11=1,v15=1) dyad (at 806.4/809.9 K), and v11=3 (at 987.9 K) are populated under warm and dense conditions, so they probe the hottest parts of the Orion-KL source. Column density and rotational and vibrational temperatures for CH$_2$CHCN in their ground and excited states, as well as for the isotopologues, have been constrained by means of a sample of more than 1000 lines in this survey. Moreover, we present the detection of methyl isocyanide (CH$_3$NC) for the first time in Orion-KL and a tentative detection of vinyl isocyanide (CH$_2$CHNC) and give column density ratios between the cyanide and isocyanide isomers.Comment: 46 pages, 22 figures, 14 tables, 9 online table

MetaNetter 2:A Cytoscape plugin for ab initio network analysis and metabolite feature classification

Metabolomics frequently relies on the use of high resolution mass spectrometry data. Classification and filtering of this data remain a challenging task due to the plethora of complex mass spectral artefacts, chemical noise, adducts and fragmentation that occur during ionisation and analysis. Additionally, the relationships between detected compounds can provide a wealth of information about the nature of the samples and the biochemistry that gave rise to them. We present a biochemical networking tool: MetaNetter 2 that is based on the original MetaNetter, a Cytoscape plugin that creates ab initio networks. The new version supports two major improvements: the generation of adduct networks and the creation of tables that map adduct or transformation patterns across multiple samples, providing a readout of compound relationships. We have applied this tool to the analysis of adduct patterns in the same sample separated under two different chromatographies, allowing inferences to be made about the effect of different buffer conditions on adduct detection, and the application of the chemical transformation analysis to both a single fragmentation analysis and an all-ions fragmentation dataset. Finally, we present an analysis of a dataset derived from anaerobic and aerobic growth of the organism Staphylococcus aureus demonstrating the utility of the tool for biological analysis

Cooling rates of chondrules from diffusion profiles in relict olivine grains

Chondrule cooling rates are one of the important constraints on chondrule formation and can be used to distinguish between different chondrule formation mechanisms. Here we have modelled diffusion profiles observed across the boundary between forsteritic-olivine relict grains and more fayalitic overgrowth. We show that the cooling of chondrules is complex and good model fits are produced with non-linear cooling rates, offering additional scope for constraining the origin of chondrules

Two-directional synthesis and biological evaluation of alkaloid 5-epi-cis-275B′

The first total synthesis of myrmicine ant alkaloid 5-epi-cis-275B0 (4) is presented. A tandem cyclisation stablished the entire core of the structure in a single transformation as well as the required 2,5-anti stereochemistry. Two-directional synthesis was used to furnish the cyclisation precursor 2, as in each of the subsequent steps towards the natural product. The first electrophysiology studies for 4 (against nicotinic acetylcholine receptors) were also conducted, finding modest inhibition of current

Orthogonally bifunctionalised polyacrylamide nanoparticles: a support for the assembly of multifunctional nanodevices

Polyacrylamide nanoparticles bearing two orthogonal reactive functionalities were prepared by reverse microemulsion polymerisation. Water-soluble photosensitisers and peptide or carbohydrate moieties were sequentially attached to the new nanospecies by orthogonal conjugations based on copper- catalysed azide-alkyne cycloaddition and isothiocyanate chemistry