Understanding Oestrogen Receptor Function in Breast Cancer and its Interaction with the Progesterone Receptor. New Preclinical Findings and their Clinical Implications.

This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.clon.2015.10.00

Damage function for historic paper. Part I: Fitness for use

Background In heritage science literature and in preventive conservation practice, damage functions are used to model material behaviour and specifically damage (unacceptable change), as a result of the presence of a stressor over time. For such functions to be of use in the context of collection management, it is important to define a range of parameters, such as who the stakeholders are (e.g. the public, curators, researchers), the mode of use (e.g. display, storage, manual handling), the long-term planning horizon (i.e. when in the future it is deemed acceptable for an item to become damaged or unfit for use), and what the threshold of damage is, i.e. extent of physical change assessed as damage. Results In this paper, we explore the threshold of fitness for use for archival and library paper documents used for display or reading in the context of access in reading rooms by the general public. Change is considered in the context of discolouration and mechanical deterioration such as tears and missing pieces: forms of physical deterioration that accumulate with time in libraries and archives. We also explore whether the threshold fitness for use is defined differently for objects perceived to be of different value, and for different modes of use. The data were collected in a series of fitness-for-use workshops carried out with readers/visitors in heritage institutions using principles of Design of Experiments. Conclusions The results show that when no particular value is pre-assigned to an archival or library document, missing pieces influenced readers/visitors’ subjective judgements of fitness-for-use to a greater extent than did discolouration and tears (which had little or no influence). This finding was most apparent in the display context in comparison to the reading room context. The finding also best applied when readers/visitors were not given a value scenario (in comparison to when they were asked to think about the document having personal or historic value). It can be estimated that, in general, items become unfit when text is evidently missing. However, if the visitor/reader is prompted to think of a document in terms of its historic value, then change in a document has little impact on fitness for use

Recognition of Face Identity and Emotion in Expressive Specific Language Impairment

Objective: To study face and emotion recognition in children with mostly expressive specific language impairment (SLI-E). Subjects and Methods: A test movie to study perception and recognition of faces and mimic-gestural expression was applied to 24 children diagnosed as suffering from SLI-E and an age-matched control group of normally developing children. Results: Compared to a normal control group, the SLI-E children scored significantly worse in both the face and expression recognition tasks with a preponderant effect on emotion recognition. The performance of the SLI-E group could not be explained by reduced attention during the test session. Conclusion: We conclude that SLI-E is associated with a deficiency in decoding non-verbal emotional facial and gestural information, which might lead to profound and persistent problems in social interaction and development. Copyright (C) 2012 S. Karger AG, Base

Proof of concept, randomized, placebo-controlled study of the effect of simvastatin on the course of age-related macular degeneration

BACKGROUND: HMG Co-A reductase inhibitors are ubiquitous in our community yet their potential role in age-related macular degeneration (AMD) remains to be determined. METHODOLOGY/PRINCIPAL FINDINGS: OBJECTIVES: To evaluate the effect of simvastatin on AMD progression and the effect modification by polymorphism in apolipoprotein E (ApoE) and complement factor H (CFH) genes. DESIGN: A proof of concept double-masked randomized controlled study. PARTICIPANTS: 114 participants aged 53 to 91 years, with either bilateral intermediate AMD or unilateral non-advanced AMD (with advanced AMD in fellow eye), BCVA ≥ 20/60 in at least one eye, and a normal lipid profile. INTERVENTION: Simvastatin 40 mg/day or placebo, allocated 1:1. MAIN OUTCOME MEASURES: Progression of AMD either to advanced AMD or in severity of non-advanced AMD. Results. The cumulative AMD progression rates were 70% in the placebo and 54% in the simvastatin group. Intent to treat multivariable logistic regression analysis, adjusted for age, sex, smoking and baseline AMD severity, showed a significant 2-fold decrease in the risk of progression in the simvastatin group: OR 0.43 (0.18-0.99), p = 0.047. Post-hoc analysis stratified by baseline AMD severity showed no benefit from treatment in those who had advanced AMD in the fellow eye before enrolment: OR 0.97 (0.27-3.52), p = 0.96, after adjusting for age, sex and smoking. However, there was a significant reduction in the risk of progression in the bilateral intermediate AMD group compared to placebo [adjusted OR 0.23 (0.07-0.75), p = 0.015]. The most prominent effect was observed amongst those who had the CC (Y402H) at risk genotype of the CFH gene [OR 0.08 (0.02-0.45), p = 0.004]. No evidence of harm from simvastatin intervention was detected. CONCLUSION/SIGNIFICANCE: Simvastatin may slow progression of non-advanced AMD, especially for those with the at risk CFH genotype CC (Y402H). Further exploration of the potential use of statins for AMD, with emphasis on genetic subgroups, is warranted. TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry (ANZCTR) ACTRN1260500032065

Why are we not flooded by involuntary thoughts about the past and future? Testing the cognitive inhibition dependency hypothesis

© The Author(s) 2018In everyday life, involuntary thoughts about future plans and events occur as often as involuntary thoughts about the past. However, compared to involuntary autobiographical memories (IAMs), such episodic involuntary future thoughts (IFTs) have become a focus of study only recently. The aim of the present investigation was to examine why we are not constantly flooded by IFTs and IAMs given that they are often triggered by incidental cues while performing undemanding activities. One possibility is that activated thoughts are suppressed by the inhibitory control mechanism, and therefore depleting inhibitory control should enhance the frequency of both IFTs and IAMs. We report an experiment with a between-subjects design, in which participants in the depleted inhibition condition performed a 60-min high-conflict Stroop task before completing a laboratory vigilance task measuring the frequency of IFTs and IAMs. Participants in the intact inhibition condition performed a version of the Stroop task that did not deplete inhibitory control. To control for physical and mental fatigue resulting from performing the 60-min Stroop tasks in experimental conditions, participants in the control condition completed only the vigilance task. Contrary to predictions, the number of IFTs and IAMs reported during the vigilance task, using the probe-caught method, did not differ across conditions. However, manipulation checks showed that participants’ inhibitory resources were reduced in the depleted inhibition condition, and participants were more tired in the experimental than in the control conditions. These initial findings suggest that neither inhibitory control nor physical and mental fatigue affect the frequency of IFTs and IAMs.Peer reviewedFinal Published versio

Search for intermediate mass black hole binaries in the first and second observing runs of the Advanced LIGO and Virgo network

Gravitational-wave astronomy has been firmly established with the detection of gravitational waves from the merger of ten stellar-mass binary black holes and a neutron star binary. This paper reports on the all-sky search for gravitational waves from intermediate mass black hole binaries in the first and second observing runs of the Advanced LIGO and Virgo network. The search uses three independent algorithms: two based on matched filtering of the data with waveform templates of gravitational-wave signals from compact binaries, and a third, model-independent algorithm that employs no signal model for the incoming signal. No intermediate mass black hole binary event is detected in this search. Consequently, we place upper limits on the merger rate density for a family of intermediate mass black hole binaries. In particular, we choose sources with total masses M=m1+m2ϵ[120,800] M and mass ratios q=m2/m1ϵ[0.1,1.0]. For the first time, this calculation is done using numerical relativity waveforms (which include higher modes) as models of the real emitted signal. We place a most stringent upper limit of 0.20 Gpc-3 yr-1 (in comoving units at the 90% confidence level) for equal-mass binaries with individual masses m1,2=100 M and dimensionless spins χ1,2=0.8 aligned with the orbital angular momentum of the binary. This improves by a factor of ∼5 that reported after Advanced LIGO's first observing run

All-sky search for short gravitational-wave bursts in the second Advanced LIGO and Advanced Virgo run

We present the results of a search for short-duration gravitational-wave transients in the data from the second observing run of Advanced LIGO and Advanced Virgo. We search for gravitational-wave transients with a duration of milliseconds to approximately one second in the 32-4096 Hz frequency band with minimal assumptions about the signal properties, thus targeting a wide variety of sources. We also perform a matched-filter search for gravitational-wave transients from cosmic string cusps for which the waveform is well modeled. The unmodeled search detected gravitational waves from several binary black hole mergers which have been identified by previous analyses. No other significant events have been found by either the unmodeled search or the cosmic string search. We thus present the search sensitivities for a variety of signal waveforms and report upper limits on the source rate density as a function of the characteristic frequency of the signal. These upper limits are a factor of 3 lower than the first observing run, with a 50% detection probability for gravitational-wave emissions with energies of ∼10-9 Mc2 at 153 Hz. For the search dedicated to cosmic string cusps we consider several loop distribution models, and present updated constraints from the same search done in the first observing run

Search for Eccentric Binary Black Hole Mergers with Advanced LIGO and Advanced Virgo during Their First and Second Observing Runs

When formed through dynamical interactions, stellar-mass binary black holes (BBHs) may retain eccentric orbits (e > 0.1 at 10 Hz) detectable by ground-based gravitational-wave detectors. Eccentricity can therefore be used to differentiate dynamically formed binaries from isolated BBH mergers. Current template-based gravitational-wave searches do not use waveform models associated with eccentric orbits, rendering the search less efficient for eccentric binary systems. Here we present the results of a search for BBH mergers that inspiral in eccentric orbits using data from the first and second observing runs (O1 and O2) of Advanced LIGO and Advanced Virgo. We carried out the search with the coherent WaveBurst algorithm, which uses minimal assumptions on the signal morphology and does not rely on binary waveform templates. We show that it is sensitive to binary mergers with a detection range that is weakly dependent on eccentricity for all bound systems. Our search did not identify any new binary merger candidates. We interpret these results in light of eccentric binary formation models. We rule out formation channels with rates ⪆100 Gpc-3 yr-1 for e > 0.1, assuming a black hole mass spectrum with a power-law index ≲2

Spontaneous and deliberate future thinking: A dual process account

© 2019 Springer Nature.This is the final published version of an article published in Psychological Research, licensed under a Creative Commons Attri-bution 4.0 International License. Available online at: https://doi.org/10.1007/s00426-019-01262-7.In this article, we address an apparent paradox in the literature on mental time travel and mind-wandering: How is it possible that future thinking is both constructive, yet often experienced as occurring spontaneously? We identify and describe two ‘routes’ whereby episodic future thoughts are brought to consciousness, with each of the ‘routes’ being associated with separable cognitive processes and functions. Voluntary future thinking relies on controlled, deliberate and slow cognitive processing. The other, termed involuntary or spontaneous future thinking, relies on automatic processes that allows ‘fully-fledged’ episodic future thoughts to freely come to mind, often triggered by internal or external cues. To unravel the paradox, we propose that the majority of spontaneous future thoughts are ‘pre-made’ (i.e., each spontaneous future thought is a re-iteration of a previously constructed future event), and therefore based on simple, well-understood, memory processes. We also propose that the pre-made hypothesis explains why spontaneous future thoughts occur rapidly, are similar to involuntary memories, and predominantly about upcoming tasks and goals. We also raise the possibility that spontaneous future thinking is the default mode of imagining the future. This dual process approach complements and extends standard theoretical approaches that emphasise constructive simulation, and outlines novel opportunities for researchers examining voluntary and spontaneous forms of future thinking.Peer reviewe