Sting of passion

A new exhibition of contemporary jewellery by 12 up-and-coming international jewellery artists opens at Manchester Art Gallery this July. Curated by Manchester-based jewellery artist Jo Bloxham, the exhibition features new conceptual works of jewellery by artists from as far afield as the USA and Mexico. All the works on display have been inspired by Pre-Raphaelite paintings from Manchester Art Gallery’s prestigious collections. The paintings have all been selected by the exhibition curator, Jo Bloxham and include Pre-Raphaelite favourites such as Arthur Hughes’ Ophelia and Rossetti’s The Bower Meadow and Astarte Syriaca. The works portray women as a femme fatale, a seductress, and in some cases, purely as an object of beauty. Bloxham comments that each of the jewellers has responded individually, the works have provoked some strong reactions, and astonishing results: “The jewellers have created an exciting body of work using a diverse selection of materials, from gold and garnets to concrete and broken glass. The Sting of Passion is an opportunity to explore an area of jewellery design rarely seen in the UK.” Polish jeweller, Arek Wolski has added modern irony to his work for Eve Tempted by John Stanhope. Playing on words, Wolski has created a t-shirt brooch, changing the phrase ‘Last Forever’ to a more cynical ‘Lust Forever’. French jeweller, Benjamin Lignel found The Bower Meadow by Dante Gabriel Rossetti deeply unsettling. Lignel says “Here are the real desperate housewives: typecast for maximum excitement. Rossetti’s dancing beauties live the test-tube lives of neutered she-monsters in a tree-lined water-tank.” Nanna Melland from Germany has created a fine, gold chain, to sit around the waist of Rossetti’s Astarte Syriaca in the form of a new girdle

DNA methylation of FKBP5 and response to exposure-based psychological therapy

Differential DNA methylation of the HPA-axis related gene FKBP5 has recently been shown to be associated with varying response to environmental influences, and may play a role in how well people respond to psychological treatments. Participants (n=111) received exposure-based CBT for agoraphobia with or without panic disorder, or specific phobias. Percentage DNA methylation levels were measured for the promoter region and intron 7 of FKBP5. The association between percentage reduction in clinical severity and change in DNA methylation was tested using linear mixed models. The effect of genotype (rs1360780) was tested by the inclusion of an interaction term. The association between change in DNA methylation and FKBP5 expression was examined. Change in percentage DNA methylation at one CpG site of intron 7 was associated with percentage reduction in severity (β=-4.26, p=3.90x10-4), where a decrease in DNA methylation was associated with greater response to therapy. An interaction was detected between rs1360780 and changes in DNA methylation in the promoter region of FKBP5 on treatment outcome (p=0.045), but did not survive correction for multiple testing. Changes in DNA methylation were not associated with FKBP5 expression. Decreasing DNA methylation at one CpG site of intron 7 of FKBP5 was strongly associated with decreasing anxiety severity following exposure-based CBT. In addition, there was suggestive evidence that allele-specific methylation at the promoter region may also be associated with treatment response. The results of this study add to the growing literature demonstrating the role of biological processes such as DNA methylation in response to environmental influences

Impact of coadministration of proton-pump inhibitors and palbociclib in hormone receptor-positive/HER2-negative advanced breast cancer

Background: The capsule formulation of CDK4/6 inhibitor palbociclib has reduced solubility at gastric pH > 4.5 and may have decreased activity when used with proton-pump inhibitors (PPI). Herein, we report the effect of PPI on palbociclib capsule activity and safety in the PARSIFAL study. Methods: First -line endocrine-sensitive, hormone receptor-positive (HR +)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) patients received palbociclib capsules plus fulvestrant or letrozole. The primary endpoint was progression-free survival (PFS). This post-hoc analysis compared PPI use. Patients were PPI-na & iuml;ve (N-PPI) if not on PPI during the study, and either early (E-PPI) or long-term PPI (LT-PPI) if on PPI at study entry or for at least >= 2/3 of treatment, respectively. PPI groups were not mutually exclusive. Results: Among 486 patients, 66.9 % were N-PPI, 13.2 % E-PPI, 18.7 % LT-PPI, and 11.5 % of the PPI users were defined as neither. Median PFS (mPFS) was 29.6 months in the study population, 28.7 months in N-PPI, 23.0 months in E-PPI (Hazard Ratio [HR] 1.5; 95%Confidence Interval [CI] 1.1 -2.2; p = 0.024), and 23.0 months in LT-PPI (HR 1.4; 95%CI 1.0 -1.9; p = 0.035). By landmark analysis, PPI use was associated with poorer mPFS at 3 and 12 months. Grade >= 3 hematological adverse events occurred in 71.7 % of N-PPI, 57.8 % of E-PPI (p = 0.021), and 54.9 % of LT-PPI (p = 0.003). Dose reductions and dosing delays due to hematological toxicity occurred in 70.8 % of N-PPI, 56.3 % of E-PPI (p = 0.018), and 52.7 % of LT-PPI (p = 0.002). Conclusions: PPI use may reduce palbociclib capsule toxicity, dose modifications, and clinical activity in HR +/ HER2- ABC

The SuperCam Instrument Suite on the Mars 2020 Rover: Science Objectives and Mast-Unit Description

On the NASA 2020 rover mission to Jezero crater, the remote determination of the texture, mineralogy and chemistry of rocks is essential to quickly and thoroughly characterize an area and to optimize the selection of samples for return to Earth. As part of the Perseverance payload, SuperCam is a suite of five techniques that provide critical and complementary observations via Laser-Induced Breakdown Spectroscopy (LIBS), Time-Resolved Raman and Luminescence (TRR/L), visible and near-infrared spectroscopy (VISIR), high-resolution color imaging (RMI), and acoustic recording (MIC). SuperCam operates at remote distances, primarily 2-7 m, while providing data at sub-mm to mm scales. We report on SuperCam's science objectives in the context of the Mars 2020 mission goals and ways the different techniques can address these questions. The instrument is made up of three separate subsystems: the Mast Unit is designed and built in France; the Body Unit is provided by the United States; the calibration target holder is contributed by Spain, and the targets themselves by the entire science team. This publication focuses on the design, development, and tests of the Mast Unit; companion papers describe the other units. The goal of this work is to provide an understanding of the technical choices made, the constraints that were imposed, and ultimately the validated performance of the flight model as it leaves Earth, and it will serve as the foundation for Mars operations and future processing of the data.In France was provided by the Centre National d'Etudes Spatiales (CNES). Human resources were provided in part by the Centre National de la Recherche Scientifique (CNRS) and universities. Funding was provided in the US by NASA's Mars Exploration Program. Some funding of data analyses at Los Alamos National Laboratory (LANL) was provided by laboratory-directed research and development funds

Relatório de estágio em farmácia comunitária

Relatório de estágio realizado no âmbito do Mestrado Integrado em Ciências Farmacêuticas, apresentado à Faculdade de Farmácia da Universidade de Coimbr

Thermally-induced aggregation and fusion of protein-free lipid vesicles

\u3cp\u3eMembrane fusion is an important phenomenon in cell biology and pathology. This phenomenon can be modeled using vesicles of defined size and lipid composition. Up to now fusion models typically required the use of chemical (polyethyleneglycol, cations) or enzymatic catalysts (phospholipases). We present here a model of lipid vesicle fusion induced by heat. Large unilamellar vesicles consisting of a phospholipid (dioleoylphosphatidylcholine), cholesterol and diacylglycerol in a 43:57:3mol ratio were employed. In this simple system, fusion was the result of thermal fluctuations, above 60°C. A similar system containing phospholipid and cholesterol but no diacylglycerol was observed to aggregate at and above 60°C, in the absence of fusion. Vesicle fusion occurred under our experimental conditions only when \u3csup\u3e31\u3c/sup\u3eP NMR and cryo-transmission electron microscopy of the lipid mixtures used in vesicle preparation showed non-lamellar lipid phase formation (hexagonal and cubic). Non-lamellar structures are probably the result of lipid reassembly of the products of individual fusion events, or of fusion intermediates. A temperature-triggered mechanism of lipid reassembly might have occurred at various stages of protocellular evolution.\u3c/p\u3

Annals of Hematology / Fibrinolysis in patients with a mild-to-moderate bleeding tendency of unknown cause

In more than 50% of patients with a mild-to-moderate bleeding tendency, no underlying cause can be identified (bleeding of unknown cause, BUC). Data on parameters of fibrinolysis in BUC are scarce in the literature and reveal discrepant results. It was the aim of this study to investigate increased fibrinolysis as a possible mechanism of BUC. We included 270 patients (227 females, median age 44 years, 2575th percentile 3258) with BUC and 98 healthy controls (65 females, median age 47 years, 2575thpercentile 3955). Tissue plasminogen activator (tPA-) antigen and activity, plasminogen activator inhibitor type-1 (PAI-1), tPA-PAI-1 complexes, thrombin activatable fibrinolysis inhibitor (TAFI), 2-antiplasmin, and D-dimer were determined. While PAI-1 deficiency was equally frequent in patients with BUC and controls (91/270, 34%, and 33/98, 34%, p = 0.996), tPA activity levels were more often above the detection limit in patients than in controls (103/213, 48%, and 23/98, 23%, p < 0.0001). We found lower levels of tPA-PAI-1 complexes (6.86 (3.9910.00) and 9.11 (7.1713.12), p < 0.001) and higher activity of TAFI (18.61 (15.8022.58) and 17.03 (14.0220.02), p < 0.001) and 2-antiplasmin (102 (94109) and 98 (90106], p = 0.003) in patients compared to controls. Detectable tPA activity (OR 3.02, 95%CI 1.755.23, p < 0.0001), higher levels of TAFI (OR 2.57, 95%CI 1.484.46, p = 0.0008) and 2-antiplasmin (OR 1.03, 95%CI 1.011.05, p = 0.011), and lower levels of tPA-PAI-1 complexes (OR 0.90, 95%CI 0.860.95, p < 0.0001) were independently associated with BUC in sex-adjusted logistic regression analyses. We conclude that the fibrinolytic system can play an etiological role for bleeding in patients with BUC.(VLID)349866