pinecone/core-2020-05-10-deduplication huggingface dataset:
Tamoxifen for prevention of breast cancer: extended long-term follow-up of the IBIS-I breast cancer prevention trial.

Â© Cuzick et al. Open Access article distributed under the terms of CC BY.http://dx.doi.org/10.1016/S1470-2045(14)71171-4BACKGROUND: Four previously published randomised clinical trials have shown that tamoxifen can reduce the risk of breast cancer in healthy women at increased risk of breast cancer in the first 10 years of follow-up. We report the long-term follow-up of the IBIS-I trial, in which the participants and investigators remain largely masked to treatment allocation. METHODS: In the IBIS-I randomised controlled trial, premenopausal and postmenopausal women 35-70 years of age deemed to be at an increased risk of developing breast cancer were randomly assigned (1:1) to receive oral tamoxifen 20 mg daily or matching placebo for 5 years. Patients were randomly assigned to the two treatment groups by telephone or fax according to a block randomisation schedule (permuted block sizes of six or ten). Patients and investigators were masked to treatment assignment by use of central randomisation and coded drug supply. The primary endpoint was the occurrence of breast cancer (invasive breast cancer and ductal carcinoma in situ), analysed by intention to treat. Cox proportional hazard models were used to assess breast cancer occurrence and mortality. The trial is closed to recruitment and active treatment is completed, but long-term follow-up is ongoing. This trial is registered with controlledtrials.com, number ISRCTN91879928. FINDINGS: Between April 14, 1992, and March 30, 2001, 7154 eligible women recruited from genetics clinics and breast care clinics in eight countries were enrolled into the IBIS-I trial and were randomly allocated to the two treatment groups: 3579 to tamoxifen and 3575 to placebo. After a median follow up of 16.0 years (IQR 14.1-17.6), 601 breast cancers have been reported (251 [7.0%] in 3579 patients in the tamoxifen group vs 350 [9.8%] in 3575 women in the placebo group; hazard ratio [HR] 0.71 [95% CI 0.60-0.83], p<0.0001). The risk of developing breast cancer was similar between years 0-10 (226 [6.3%] in 3575 women in the placebo group vs 163 [4.6%] in 3579 women in the tamoxifen group; hazard ratio [HR] 0.72 [95% CI 0.59-0.88], p=0.001) and after 10 years (124 [3.8%] in 3295 women vs 88 [2.6%] in 3343, respectively; HR 0.69 [0.53-0.91], p=0.009). The greatest reduction in risk was seen in invasive oestrogen receptor-positive breast cancer (HR 0.66 [95% CI 0.54-0.81], p<0.0001) and ductal carcinoma in situ (0.65 [0.43-1.00], p=0.05), but no effect was noted for invasive oestrogen receptor-negative breast cancer (HR 1.05 [95% CI 0.71-1.57], p=0.8). INTERPRETATION: These results show that tamoxifen offers a very long period of protection after treatment cessation, and thus substantially improves the benefit-to-harm ratio of the drug for breast cancer prevention. FUNDING: Cancer Research UK (UK) and the National Health and Medical Research Council (Australia)
SUSYFLAVOR v2: A Computational tool for FCNC and CP-violating processes in the MSSM

We present SUSY_FLAVOR version 2 — a Fortran 77 program that calculates low-energy flavor observables\ud
in the general R-parity conserving MSSM. For a set of MSSM parameters as input, the code gives\ud
predictions for:\ud
1. Electric dipole moments of the leptons and the neutron.\ud
2. Anomalous magnetic moments (i.e. g − 2) of the leptons.\ud
3. Radiative lepton decays (μ → eγ and τ → μγ , eγ ).\ud
4. Rare Kaon decays (K0\ud
L → π0 ¯νν and K+ → π+ ¯νν).\ud
5. Leptonic B decays (Bs,d → l+l−, B → τ ν and B → Dτ ν).\ud
6. Radiative B decays (B → ¯ Xsγ ).\ud
7. ΔF = 2 processes ( ¯ K0–K0, ¯D–D, ¯Bd–Bd and ¯Bs–Bs mixing).\ud
Comparing to SUSY_FLAVOR v1, where the matching conditions were calculated strictly at one-loop level,\ud
SUSY_FLAVOR v2 performs the resummation of all chirally enhanced corrections, i.e. takes into account\ud
the enhanced effects from tan β and/or large trilinear soft mixing terms to all orders in perturbation\ud
theory. Also, in SUSY_FLAVOR v2 new routines calculation of B → (D)τ ν, g − 2, radiative lepton decays\ud
and Br(l → l′γ ) were added. All calculations are done using exact diagonalization of the sfermion mass\ud
matrices. The program can be obtained from http://www.fuw.edu.pl/susy_flavor
CALIFA, the Calar Alto Legacy Integral Field Area survey III. Second public data release

This paper describes the Second Public Data Release (DR2) of the Calar Alto Legacy Integral Field Area (CALIFA) survey. The data for 200 objects are made public, including the 100 galaxies of the First Public Data Release (DR1). Data were obtained with the integral-field spectrograph PMAS /PPak mounted on the 3.5 m telescope at the Calar Alto observatory. Two different spectral setups are available for each galaxy, (i) a low-resolution V500 setup covering the wavelength range 3745-7500 Å with a spectral resolution of 6.0 Å (FWHM); and (ii) a medium-resolution V1200 setup covering the wavelength range 3650-4840 Å with a spectral resolution of 2.3 Å (FWHM). The sample covers a redshift range between 0.005 and 0.03, with a wide range of properties in the color-magnitude diagram, stellar mass, ionization conditions, and morphological types. All the cubes in the data release were reduced with the latest pipeline, which includes improved spectrophotometric calibration, spatial registration, and spatial resolution. The spectrophotometric calibration is better than 6% and the median spatial resolution is 2´´ 4. In total, the second data release contains over 1.5 million spectra
Vasopressor meets vasodepressor: The AT1-B2 receptor heterodimer

The AT1 receptor for the vasopressor angiotensin II is one of the most important drug targets for the treatment of cardiovascular diseases. Sensitization of the AT1 receptor system is a common feature contributing to the pathogenesis of many cardiovascular disorders but underlying mechanisms are not fully understood. More than a decade ago, evidence was provided for control of AT1R activation by heterodimerization with the B2 receptor for the vasodepressor peptide, bradykinin, a physiological counterpart of the vasoconstrictor angiotensin II. AT1-B2 receptor heterodimerization was shown to enhance AT1R-stimulated signaling under pathophysiological conditions such as experimental and human pregnancy hypertension. Notably, AT1R signal sensitization of patients with preeclampsia hypertension was attributed to AT1R-B2R heterodimerization. Vice versa, transgenic mice lacking the AT1-B2 receptor heterodimer due to targeted deletion of the B2R gene showed a significantly reduced AT1R-stimulated vasopressor response compared to transgenic mice with abundant AT1R-B2R heterodimerization. Biophysical methods such as BRET and FRET confirmed those data by demonstrating efficient AT1-B2 receptor heterodimerization in transfected cells and transgenic mice. Recently, a study on AT1R-specific biased agonism directed the focus to the AT1-B2 receptor heterodimer again. The β-arrestin-biased [Sar1,Ile4,Ile8]-angiotensin II promoted not only the recruitment of β-arrestin to the AT1R but also stimulated the down-regulation of the AT1R-associated B2 receptor by co-internalization. Thereby specific targeting of the AT1R-B2R heterodimer became feasible and could open the way to a new class of drugs, which specifically interfere with pathological angiotensin II-AT1 receptor system activation
A single-blinded, randomized clinical trial of how to implement an evidence-based treatment for generalized anxiety disorder [IMPLEMENT] - effects of three different strategies of implementation

BACKGROUND: Despite long-standing calls to disseminate evidence-based treatments for generalized anxiety (GAD), modest progress has been made in the study of how such treatments should be implemented. The primary objective of this study was to test three competing strategies on how to implement a cognitive behavioral treatment (CBT) for out-patients with GAD (i.e., comparison of one compensation vs. two capitalization models).\ud
METHODS: For our three-arm, single-blinded, randomized controlled trial (implementation of CBT for GAD [IMPLEMENT]), we recruited adults with GAD using advertisements in high-circulation newspapers to participate in a 14-session cognitive behavioral treatment (Mastery of your Anxiety and Worry, MAW-packet). We randomly assigned eligible patients using a full randomization procedure (1:1:1) to three different conditions of implementation: adherence priming (compensation model), which had a systematized focus on patients' individual GAD symptoms and how to compensate for these symptoms within the MAW-packet, and resource priming and supportive resource priming (capitalization model), which had systematized focuses on patients' strengths and abilities and how these strengths can be capitalized within the same packet. In the intention-to-treat population an outcome composite of primary and secondary symptoms-related self-report questionnaires was analyzed based on a hierarchical linear growth model from intake to 6-month follow-up assessment. This trial is registered at ClinicalTrials.gov (identifier: NCT02039193) and is closed to new participants.\ud
FINDINGS: From June 2012 to Nov. 2014, from 411 participants that were screened, 57 eligible participants were recruited and randomly assigned to three conditions. Forty-nine patients (86%) provided outcome data at post-assessment (14% dropout rate). All three conditions showed a highly significant reduction of symptoms over time. However, compared with the adherence priming condition, both resource priming conditions indicated faster symptom reduction. The observer ratings of a sub-sample of recorded videos (n = 100) showed that the therapists in the resource priming conditions conducted more strength-oriented interventions in comparison with the adherence priming condition. No patients died or attempted suicide.\ud
INTERPRETATION: To our knowledge, this is the first trial that focuses on capitalization and compensation models during the implementation of one prescriptive treatment packet for GAD. We have shown that GAD related symptoms were significantly faster reduced by the resource priming conditions, although the limitations of our study included a well-educated population. If replicated, our results suggest that therapists who implement a mental health treatment for GAD might profit from a systematized focus on capitalization models.\ud
FUNDING: Swiss Science National Foundation (SNSF-Nr. PZ00P1_136937/1) awarded to CF
Magnetothermoelectric response from holography

In this note we study the effects of a magnetic field on transport using holographic models with broken translational invariance. We show that, after carefully sub-tracting off non-trivial magnetisation currents, it is possible to express the DC transport currents of the boundary theory in terms of properties of a black hole horizon. This allows us to obtain simple analytic expressions for the electrical, thermoelectric and heat conductivity tensors. Our results apply to both isotropic and anisotropic models, including holographic Q-lattices and to certain theories where translational invariance is broken by linear sources for axions
An interactive exhibit to assist with understanding of project delays

Time, a dynamic concept, can be difficult to understand in static form. As a consequence, the proactive management and retrospective analysis of delays on construction projects can prove challenging using conventional methods. This can result in time overruns and the rejection of valid delay claims that can develop into dispute if they are not resolved. Disputes have a negative effect on the construction industry, but their occurrence, value, and duration are rising. This research aims to reduce the likelihood and severity of common delay disputes by providing a solution that aims to (1) assist with the proactive management of delays; and (2) improve the presentation of delay claim information. A detailed background study was undertaken that identified technological opportunities and modes of presentation as potential ways of overcoming the challenges associated with managing and analyzing delays. Two stages of assessment were then undertaken to determine the suitability and application of these findings. The first stage used a workshop with 50 construction adjudicators to determine the appropriateness of modes of presentation in assisting construction claims. The second stage developed the workshop findings with previous research and integrated modes of presentation with delay analysis. The output was an interactive exhibit that was assessed through a simulation based on case study data. The interactive exhibit is intended to support, not replace, traditional methods of delay analysis; however, the solution has difficulties with technology as well as the challenge of creating a holistic tool for both proactive management and retrospective analysis. It is perceived that the interactive exhibit will add most value to the resolution of construction delay claims, but that further investigation is required to validate the proposed concept before it is used in practice
Identifying non-stationary groundwater level responses to North Atlantic ocean-atmosphere teleconnection patterns using wavelet coherence

The first comprehensive use of wavelet methods to identify non-stationary time-frequency relations between North Atlantic ocean-atmosphere teleconnection patterns and groundwater levels is described. Long-term hydrogeological time series from three boreholes within different aquifers across the UK are analysed to identify statistically significant wavelet coherence between the North Atlantic Oscillation, East Atlantic pattern, and the Scandinavia pattern and monthly groundwater-level time series. Wavelet coherence measures the cross-correlation of two time series as a function of frequency, and can be interpreted as a correlation coefficient value. Results not only indicate that there are common statistically significant periods of multiannual-to-decadal wavelet coherence between the three teleconnection indices and groundwater levels in each of the boreholes, but they also show that there are periods when groundwater levels at individual boreholes show distinctly different patterns of significant wavelet coherence with respect to the teleconnection indices. The analyses presented demonstrate the value of wavelet methods in identifying the synchronization of groundwater-level dynamics by non-stationary climate variability on time scales that range from interannual to decadal or longer
Current concept of reverse cholesterol transport and novel strategy for atheroprotection.

Elevated levels of low-density lipoprotein cholesterol (LDL-C) increase the risk of coronary heart disease (CHD), but pharmacologic therapy to decrease LDL-C significantly reduces the risk of cardiovascular events. Despite the effectiveness of statin therapy, there remains significant residual cardiovascular risk. A low plasma concentration of high-density lipoprotein cholesterol (HDL-C) is associated with increased risk of CHD. Moreover, recent studies have shown that HDL-C levels during statin treatment remain an independent predictor of the risk of cardiovascular events. However, recent clinical trials aimed at reducing CHD risk by raising HDL-C levels have not shown satisfactory results and it is becoming evident that a functional HDL-C is a more desirable target than simply elevating its level. This review summarizes the function of HDL-C in reverse cholesterol transfer from peripheral tissue and discusses the latest HDL-targeting therapeutic strategies including the manipulation of microRNAs
Development of polymeric hollow fiber membranes containing catalytic metal nanoparticles

Metal nanoparticles (MNPs) have unique physico-chemical properties advantageous for catalytic applications which differ from bulk material. However, the main drawback of MNPs is their insufficient stability due to a high trend for aggregation. To cope with this inconvenience, the stabilization of MNPs in polymeric matrices has been tested. This procedure is a promising strategy to maintain catalytic properties.\ud
\ud
The aim of this work is the synthesis of polymer-stabilized MNPs inside functionalized polymeric membranes in order to build catalytic membrane reactors. First, the polymeric support must have functional groups capable to retain nanoparticle precursors (i.e. sulfonic), then, nanoparticles can grow inside the polymeric matrix by chemical reduction of metal ions.\ud
\ud
Two different strategies have been used in this work. Firstly, polyethersulfone microfiltration hollow fibers have been modified by applying polyelectrolyte multilayers. Secondly, polysulfone ultrafiltration membranes were modified by UV-photografting using sodium p-styrene sulfonate as a vinyl monomer. The catalytic performance of developed hollow fibers has been evaluated by using the reduction of nitrophenol to aminophenol by sodium borohydride. Hollow fiber modules with Pd MNPs have been tested in dead-end and cross-flow filtration. Complete nitrophenol degradation is possible depending on operation parameters such as applied pressure and permeate flux.Postprint (author’s final draft
High precision X-ray log N - Log S distributions: Implications for the obscured AGN population

Context. Our knowledge of the properties of AGN, especially those of optical type-2 objects, is very incomplete. Because extragalactic\ud
source count distributions are dependent on the cosmological and statistical properties of AGN, they provide a direct method of\ud
investigating the underlying source populations.\ud
Aims. We aim to constrain the extragalactic source count distributions over a broad range of X-ray fluxes and in various energy bands\ud
to test whether the predictions from X-ray background synthesis models agree with the observational constraints provided by our\ud
measurements.\ud
Methods. We have used 1129 XMM-Newton observations at |b| > 20◦ covering a total sky area of 132.3 deg2 to compile the largest\ud
complete samples of X-ray selected objects to date both in the 0.5−1 keV, 1−2 keV, 2−4.5 keV, 4.5−10 keV bands employed in\ud
standard XMM-Newton data processing and in the 0.5−2 keV and 2−10 keV energy bands more usually considered in source count\ud
studies. Our survey includes in excess of 30 000 sources and spans fluxes from ∼10−15 to 10−12 erg cm−2 s−1 below 2 keV and from\ud
∼10−14 to 10−12 erg cm−2 s−1 above 2 keV where the bulk of the cosmic X-ray background energy density is produced.\ud
Results. The very large sample size we obtained means our results are not limited by cosmic variance or low counting statistics. A\ud
break in the source count distributions was detected in all energy bands except the 4.5−10 keV band. We find that an analytical model\ud
comprising 2 power-law components cannot adequately describe the curvature seen in the source count distributions. The shape of\ud
the log N(>S ) − log S is strongly dependent on the energy band with a general steepening apparent as we move to higher energies.\ud
This is due to the fact that non-AGN populations, comprised mainly of stars and clusters of galaxies, contribute up to 30% of the\ud
source population at energies <2 keV and at fluxes ≥10−13 erg cm−2 s−1, and these populations of objects have significantly flatter\ud
source count distributions than AGN. We find a substantial increase in the relative fraction of hard X-ray sources at higher energies,\ud
from ≥55% below 2 keV to ≥77% above 2 keV. However, the majority of sources detected above 4.5 keV still have significant flux\ud
below 2 keV. Comparison with predictions from the synthesis models suggest that the models might be overpredicting the number of\ud
faint absorbed AGN, which would call for fine adjustment of some model parameters such as the obscured to unobscured AGN ratio\ud
and/or the distribution of column densities at intermediate obscuration.866
Targeting of the Arpc3 actin nucleation factor by miR-29a/b regulates dendritic spine morphology

PMCID: PMC3207289Previous studies have demonstrated that microribonucleic acids (miRs) are key regulators of protein expression in the brain and modulate dendritic spine morphology and synaptic activity. To identify novel miRs involved in neuronal plasticity, we exposed adult mice to chronic treatments with nicotine, cocaine, or amphetamine, which are psychoactive drugs that induce well-documented neuroadaptations. We observed brain region- and drug-specific changes in miR expression levels and identified miR-29a/b as regulators of synaptic morphology. In vitro imaging experiments indicated that miR-29a/b reduce mushroom-shaped dendritic spines on hippocampal neurons with a concomitant increase in filopodial-like outgrowths, suggesting an effect on synapse formation via actin cytoskeleton remodeling. We identified Arpc3, a component of the ARP2/3 actin nucleation complex, as a bona fide target for down-regulation by miR-29a/b. This work provides evidence that targeting of Arpc3 by miR-29a/b fine tunes structural plasticity by regulating actin network branching in mature and developing spines.Peer-reviewedPublisher Version7625
Vacuum metastability with black holes.

We consider the possibility that small black holes can act as nucleation seeds for the decay of a metastable vacuum, focussing particularly on the Higgs potential. Using a thin-wall bubble approximation for the nucleation process, which is possible when generic quantum gravity corrections are added to the Higgs potential, we show that primordial black holes can stimulate vacuum decay. We demonstrate that for suitable parameter ranges, the vacuum decay process dominates over the Hawking evaporation process. Finally, we comment on the application of these results to vacuum decay seeded by black holes produced in particle collisions
High-level over-expression, purification, and crystallization of a novel phospholipase C/sphingomyelinase from Pseudomonas aeruginosa.

The hemolytic phospholipase C/sphingomyelinase PlcH from the opportunistic pathogen Pseudomonas aeruginosa represents the founding member of a growing family of virulence factors identified in a wide range of bacterial and fungal pathogens. In P. aeruginosa PlcH is co-expressed with a 17 kDa chaperone (PlcR2) and secreted as a fully folded heterodimer (PlcHR2) of approximately 95 kDa, by the twin arginine translocase (TAT) via the cytoplasmic membrane and through the outer membrane, by the Xcp (TypeII) secretory system. PlcHR2 has been shown to be an important virulence factor in model P. aeruginosa infections and is selectively cytotoxic, at picomolar concentrations to mammalian endothelial cells. Here we report how the various challenges starting from protein overexpression in the native organism P. aeruginosa, the use of detergents in the crystallization and data collection using the most advanced μ-focus synchrotron beam lines were overcome. Native diffraction data of this heterodimeric protein complex were collected up to a resolution of 4 Å, whereas needle-shaped crystals of l-selenomethionine substituted PlcHR2 with a maximum diameter of 10 micron were used to collect data sets with a maximum resolution of 2.75 Å
Associated production of a top pair and a Higgs boson beyond NLO

We consider soft gluon emission corrections to the production of a
top-antitop pair in association with a Higgs boson at hadron colliders. In
particular, we present a soft-gluon resummation formula for this production
process and gather all elements needed to evaluate it at
next-to-next-to-leading logarithmic order. We employ these results to obtain
approximate next-to-next-to-leading order (NNLO) formulas, and implement them
in a bespoke parton-level Monte Carlo program which can be used to calculate
the total cross section along with arbitrary differential distributions. We use
this tool to study the phenomenological impact of the approximate NNLO
corrections, finding that they increase the total cross section and the
differential distributions which we evaluated in this work.Comment: 35 pages, 5 tables and 12 figures. Version published in JHEP 1603
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