Could NICE guidance on the choice of blood pressure lowering drugs be simplified?

Reecha Sofat and colleagues argue that prescribing advice needs updating in the light of recent evidence that all classes of blood pressure lowering drugs are broadly equivalen

Enhanced X-ray variability from V1647 Ori, the young star in outburst illuminating McNeil's Nebula

We report a ~38 ks X-ray observation of McNeil's Nebula obtained with XMM on 2004 April 4. V1647 Ori, the young star in outburst illuminating McNeil's Nebula, is detected with XMM and appears variable in X-rays. We investigate the hardness ratio variability and time variations of the event energy distribution with quantile analysis, and show that the large increase of the count rate from V1647 Ori observed during the second half of the observation is not associated with any large plasma temperature variations as for typical X-ray flares from young low-mass stars. X-ray spectral fitting shows that the bulk (~75%) of the intrinsic X-ray emission in the 0.5-8 keV energy band comes from a soft plasma component (0.9 keV) reminiscent of the X-ray spectrum of the classical T Tauri star TW Hya, for which X-ray emission is believed to be generated by an accretion shock onto the photosphere of a low-mass star. The hard plasma component (4.2 keV) contributes ~25% of the total X-ray emission, and can be understood only in the framework of plasma heating sustained by magnetic reconnection events. We find a hydrogen column density of NH=4.1E22 cm-2, which points out a significant excess of hydrogen column density compared to the value derived from optical/IR observations, consistent with the picture of the rise of a wind/jet unveiled from ground optical spectroscopy. The X-ray flux observed with XMM ranges from roughly the flux observed by Chandra on 2004 March 22 (~10 times greater than the pre-outburst X-ray flux) to a value two times greater than that caught by Chandra on 2004 March 7 (~200 times greater than the pre-outburst X-ray flux). We have investigated the possibility that V1647 Ori displays a periodic variation in X-ray brightness as suggested by the combined Chandra+XMM data set (abridged).Comment: 11 pages and 8 Figures. Accepted for publication by Astronomy & Astrophysic

Oral Bisphosphonates and Risk of Atrial Fibrillation and Flutter in Women: A Self-Controlled Case-Series Safety Analysis

Background: A recent trial unexpectedly reported that atrial fibrillation, when defined as serious, occurred more often in participants randomized to an annual infusion of the relatively new parenteral bisphosphonate, zoledronic acid, than among those given placebo, but had limited power. Two subsequent population-based case-control studies of patients receiving a more established oral bisphosphonate, alendronic acid, reported conflicting results, possibly due to uncontrolled confounding factors.Methodology/Principal Findings: We used the United Kingdom General Practice Research Database to assess the risk of atrial fibrillation and flutter in women exposed to the oral bisphosphonates, alendronic acid and risedronate sodium. The self-controlled case-series method was used to minimise the potential for confounding. The age-adjusted incidence rate ratio for atrial fibrillation or flutter in individuals during their exposure to these oral bisphosphonates (n = 2195) was 1.07 (95% CI 0.94 - 1.21). The age-adjusted incidence rate ratio for alendronic acid (n = 1489) and risedronate sodium (n = 649) exposed individuals were 1.09 (95% CI 0.93 - 1.26) and 0.99 (95% CI 0.78 - 1.26) respectively. In post-hoc analyses, an increased risk of incident atrial fibrillation or flutter was detected for patients during their first few months of alendronic acid therapy.Conclusions/Significance: We found no robust evidence of an overall long-term increased risk of atrial fibrillation or flutter associated with continued exposure to the oral bisphosphonates, alendronic acid and risedronate sodium. A possible signal for an increase in risk during the first few months of therapy with alendronic acid needs to be re-assessed in additional studies

Trabectedin for Metastatic Soft Tissue Sarcoma: A Retrospective Single Center Analysis

Soft tissue sarcoma (STS) comprises a large variety of rare malignant tumors. Development of distant metastasis is frequent, even in patients undergoing initial curative surgery. Trabectedin, a tetrahydroisoquinoline alkaloid isolated from the Caribbean marine tunicate Ecteinascidia turbinata, was approved in 2007 for patients with advanced STS after failure of anthracyclines and ifosfamide, or for patients unsuited to receive these agents. In this study, we retrospectively analyzed 25 patients who had been treated with trabectedin at our institution between 2007 and 2010. The majority (72%) had been heavily pre-treated with ≥2 previous lines of chemotherapy. Response assessed by conventional RECIST criteria was low, with only one patient achieving a partial remission (PR) and 10 stable disease (SD) after three cycles of treatment. However, median progression-free survival (PFS) and overall survival (OS) were significantly prolonged in this population compared to non-responders, with 7.7 months versus 2.1 months (p < 0.0001; HR 15.37, 95% CI 4.3 to 54.5) and 12.13 months versus 5.54 months (p = 0.0137; HR 3.7, 95% CI 1.3 to 10.5), respectively. PFS for all patients was 58% at three months and 37% at six months. Side effects, including neutropenia, elevation of liver transaminases/liver function tests, and nausea/vomiting, were usually mild and manageable. However, dose reductions due to side effects were necessary in five patients. We conclude that trabectedin is an effective and generally well tolerated treatment for STS even in a heavily pre-treated patient population

The Use of Positron Emission Tomography in Soft Tissue Sarcoma Patients under Therapy with Trabectedin

Background: We used 2-deoxy-2-[18F] fluoro-D-glucose (FDG) positron emission tomography (PET) to evaluate the FDG uptake in patients with advanced and/or metastatic soft tissue sarcoma (STS) undergoing therapy with Ecteinascidin-743 (ET-743, Trabectedin, YondelisTM). Patients and Methods: The pilot study included nine patients with metastatic STS receiving a minimum of one cycle of treatment with trabectedin. Patients were examined using PET prior to onset of therapy and after completion of one or three cycles of trabectedin. Restaging according to Response Evaluation Criteria in Solid Tumours (RECIST) was performed in parallel using computed tomography (CT) and/or magnetic resonance imaging (MRI) and served for reference. Results: Clinical outcome of nine evaluable patients was as follows: one patient with partial remission (PR), three patients with stable disease (SD), and five patients with progressive disease (PD). A more than 40% decrease of the standardized uptake value (SUV) of sequential PET examination could be demonstrated for the responding patient (PR), whereas patients with SD or PD showed a stable SUV, but no increase in SUV. Conclusion: To our knowledge, this is the first small series of patients being treated with trabectedin and monitored using sequential PET imaging demonstrating SUV stabilization in nearly all monitored patients

An X-ray Outburst from the Rapidly Accreting Young Star That Illuminates McNeil's Nebula

Young, low-mass stars are luminous X-ray sources whose powerful X-ray flares may exert a profound influence over the process of planet formation. The origin of such emission is uncertain. Although many or perhaps most recently formed, low-mass stars emit X-rays as a consequence of solar-like coronal activity, it has also been suggested that X-ray emission may be a direct result of mass accretion onto the forming star. Here we report X-ray imaging spectroscopy observations which reveal a factor ~50 increase in the X-ray flux from a young star that is presently undergoing a spectacular optical/IR outburst. The outburst is thought to be due to the sudden onset of a phase of rapid accretion. The coincidence of a surge in X-ray brightness with the optical/IR eruption demonstrates that strongly enhanced high-energy emission from young stars can occur as a consequence of high accretion rates. We suggest that such accretion- enhanced X-ray emission from erupting young stars may be short-lived, because intense star-disk magnetospheric interactions are quenched rapidly by the subsequent accretion flood.Comment: 15 pages, 3 figures; published in Natur

Near infrared (NIR)-spectroscopy and in-vitro dissolution absorption system 2 (IDAS2) can help detect changes in the quality of generic drugs

While Health authorities in Panama strive to increase generic drug use to contain the rising costs of medicines, there is still hesitation to embrace generic drugs. Thus, regulators and drug companies need to ensure the quality, safety and efficacy of generic drugs. One prevailing concern is the absence of control over lot-to-lot changes, which may impact consistent therapeutic performance. The objective of this work was to determine whether near-infrared spectroscopy (NIR) could detect product changes. Calibration models were built using reference (standard) tablets of two products: Virax® (200 mg acyclovir) and Amlopin® (5 mg amlodipine). Then, to assess the sensitivity of NIR to product changes we compared reference versus deliberately-modified formulations of these products. Comparisons were made using principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) of NIR spectra. Several modified lots were different from reference lots, and 3D score plots showed greater discrimination by PLS-DA than PCA. The Kth nearest neighbour scores (KNN) of the modified batches were used to classify formulations as identical or not identical versus the reference. In addition, the differences detected by NIR were correlated with different in vitro dissolution and/or permeation in the in vitro dissolution absorption system 2 (IDAS2): NIR and IDAS2 yielded the same difference rank-order of difference for the modified lots tested. This study suggests that NIR and IDAS2 can help detect lots of generic drugs that differ from the reference lots. This strategy may help regulatory agencies in developing countries to safeguard patients against changes in generic products

Calibration of the charge and energy loss per unit length of the MicroBooNE liquid argon time projection chamber using muons and protons

We describe a method used to calibrate the position- and time-dependent response of the MicroBooNE liquid argon time projection chamber anode wires to ionization particle energy loss. The method makes use of crossing cosmic-ray muons to partially correct anode wire signals for multiple effects as a function of time and position, including cross-connected TPC wires, space charge effects, electron attachment to impurities, diffusion, and recombination. The overall energy scale is then determined using fully-contained beam-induced muons originating and stopping in the active region of the detector. Using this method, we obtain an absolute energy scale uncertainty of 2% in data. We use stopping protons to further refine the relation between the measured charge and the energy loss for highly-ionizing particles. This data-driven detector calibration improves both the measurement of total deposited energy and particle identification based on energy loss per unit length as a function of residual range. As an example, the proton selection efficiency is increased by 2% after detector calibration

Reconstruction and measurement of (100) MeV energy electromagnetic activity from π0 arrow γγ decays in the MicroBooNE LArTPC

We present results on the reconstruction of electromagnetic (EM) activity from photons produced in charged current νμ interactions with final state π0s. We employ a fully-automated reconstruction chain capable of identifying EM showers of (100) MeV energy, relying on a combination of traditional reconstruction techniques together with novel machine-learning approaches. These studies demonstrate good energy resolution, and good agreement between data and simulation, relying on the reconstructed invariant π0 mass and other photon distributions for validation. The reconstruction techniques developed are applied to a selection of νμ + Ar → μ + π0 + X candidate events to demonstrate the potential for calorimetric separation of photons from electrons and reconstruction of π0 kinematics

The Pandora multi-algorithm approach to automated pattern recognition of cosmic-ray muon and neutrino events in the MicroBooNE detector.

The development and operation of liquid-argon time-projection chambers for neutrino physics has created a need for new approaches to pattern recognition in order to fully exploit the imaging capabilities offered by this technology. Whereas the human brain can excel at identifying features in the recorded events, it is a significant challenge to develop an automated, algorithmic solution. The Pandora Software Development Kit provides functionality to aid the design and implementation of pattern-recognition algorithms. It promotes the use of a multi-algorithm approach to pattern recognition, in which individual algorithms each address a specific task in a particular topology. Many tens of algorithms then carefully build up a picture of the event and, together, provide a robust automated pattern-recognition solution. This paper describes details of the chain of over one hundred Pandora algorithms and tools used to reconstruct cosmic-ray muon and neutrino events in the MicroBooNE detector. Metrics that assess the current pattern-recognition performance are presented for simulated MicroBooNE events, using a selection of final-state event topologies