Suprathreshold heat pain response predicts activity-related pain, but not rest-related pain, in an exercise-induced injury model

© 2014 Coronado et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Exercise-induced injury models are advantageous for studying pain since the onset of pain is controlled and both pre-injury and post-injury factors can be utilized as explanatory variables or predictors. In these studies, rest-related pain is often considered the primary dependent variable or outcome, as opposed to a measure of activity-related pain. Additionally, few studies include pain sensitivity measures as predictors. In this study, we examined the influence of pre-injury and post-injury factors, including pain sensitivity, for induced rest and activity-related pain following exercise induced muscle injury. The overall goal of this investigation was to determine if there were convergent or divergent predictors of rest and activityrelated pain. One hundred forty-three participants provided demographic, psychological, and pain sensitivity information and underwent a standard fatigue trial of resistance exercise to induce injury of the dominant shoulder. Pain at rest and during active and resisted shoulder motion were measured at 48- and 96-hours post-injury. Separate hierarchical models were generated for assessing the influence of pre-injury and post-injury factors on 48- and 96-hour rest-related and activityrelated pain. Overall, we did not find a universal predictor of pain across all models. However, pre-injury and post-injury suprathreshold heat pain response (SHPR), a pain sensitivity measure, was a consistent predictor of activity-related pain, even after controlling for known psychological factors. These results suggest there is differential prediction of pain. A measure of pain sensitivity such as SHPR appears more influential for activity-related pain, but not rest-related pain, and may reflect different underlying processes involved during pain appraisal

Impact of CTLA-4 checkpoint antibodies on ligand binding and Transendocytosis

Anti-CTLA-4 antibodies have pioneered the field of tumour immunotherapy. However, despite impressive clinical response data, the mechanism by which anti-CTLA-4 antibodies work is still controversial. Two major checkpoint antibodies (ipilimumab and tremelimumab) have been trialled clinically. Both have high affinity binding to CTLA-4 and occupy the ligand binding site, however recently it has been suggested that in some settings such antibodies may not block ligand-CTLA-4 interactions. Here we evaluated blocking capabilities of these antibodies in a variety of settings using both soluble and cell bound target proteins. We found that when ligands (CD80 or CD86) were expressed on cells, soluble CTLA-4-Ig bound in line with affinity expectations and that this interaction was effectively disrupted by both ipilimumab and tremelimumab antibodies. Similarly, cellular CTLA-4 binding to soluble ligands was comparably prevented. We further tested the ability of these antibodies to block transendocytosis, whereby CTLA-4 captures ligands from target cells during a cognate cell-cell interaction. Once again ipilimumab and tremelimumab were similar in preventing removal of ligand by transendocytosis. Furthermore, even once transendocytosis was ongoing and cell contact was fully established, the addition of these antibodies could prevent further ligand transfer. Together these data indicate that the above checkpoint inhibitors performed in-line with predictions based on affinity and binding site data and are capable of blocking CTLA-4-ligand interactions in a wide range of settings tested

A solid state light-matter interface at the single photon level

Coherent and reversible mapping of quantum information between light and matter is an important experimental challenge in quantum information science. In particular, it is a decisive milestone for the implementation of quantum networks and quantum repeaters. So far, quantum interfaces between light and atoms have been demonstrated with atomic gases, and with single trapped atoms in cavities. Here we demonstrate the coherent and reversible mapping of a light field with less than one photon per pulse onto an ensemble of 10 millions atoms naturally trapped in a solid. This is achieved by coherently absorbing the light field in a suitably prepared solid state atomic medium. The state of the light is mapped onto collective atomic excitations on an optical transition and stored for a pre-programmed time up of to 1 mu s before being released in a well defined spatio-temporal mode as a result of a collective interference. The coherence of the process is verified by performing an interference experiment with two stored weak pulses with a variable phase relation. Visibilities of more than 95% are obtained, which demonstrates the high coherence of the mapping process at the single photon level. In addition, we show experimentally that our interface allows one to store and retrieve light fields in multiple temporal modes. Our results represent the first observation of collective enhancement at the single photon level in a solid and open the way to multimode solid state quantum memories as a promising alternative to atomic gases.Comment: 5 pages, 5 figures, version submitted on June 27 200

Ebookness

Since the mid-2000s, the ebook has stabilized into an ontologically distinct form, separate from PDFs and other representations of the book on the screen. The current article delineates the ebook from other emerging digital genres with recourse to the methodologies of platform studies and book history. The ebook is modelled as three concentric circles representing its technological, textual and service infrastructure innovations. This analysis reveals two distinct properties of the ebook: a simulation of the services of the book trade and an emphasis on user textual manipulation. The proposed model is tested with reference to comparative studies of several ebooks published since 2007 and defended against common claims of ebookness about other digital textual genres

The effects of dynamical substructure on Milky Way mass estimates from the high-velocity tail of the local stellar halo

We investigate the impact of dynamical streams and substructure on estimates of the local escape speed and total mass of Milky-Way-mass galaxies from modelling the high-velocity tail of local halo stars. We use a suite of high-resolution magnetohydrodynamical cosmological zoom-in simulations that resolve phase space substructure in local volumes around solar-like positions. We show that phase space structure varies significantly between positions in individual galaxies and across the suite. Substructure populates the high-velocity tail unevenly and leads to discrepancies in the mass estimates. We show that a combination of streams, sample noise, and truncation of the high-velocity tail below the escape speed leads to a distribution of mass estimates with a median that falls below the true value by ∼20 per cent ∼20 per cent ⁠, and a spread of a factor of 2 across the suite. Correcting for these biases, we derive a revised value for the Milky Way mass presented in Deason et al. of 1.29 +0.37 −0.47 × 10 12 M ⊙ 1.29−0.47+0.37×1012M⊙ ⁠

Individualised therapy of angiotensin converting enzyme (ACE) inhibitors in stable coronary artery disease: overview of the primary results of the PERindopril GENEtic association (PERGENE) study

In patients with stable coronary artery disease (CAD) without overt heart failure, ACE inhibitors are among the most commonly used drugs as these agents have been proven effective in reducing the risk of cardiovascular events. Considerable individual variations in the blood pressure response to ACE inhibitors are observed and as such heterogeneity in clinical treatment effect would be likely as well. Assessing the consistency of treatment benefit is essential for the rational and cost-effective prescription of ACE inhibitors. Information on heterogeneities in treatment effect between subgroups of patients could be used to develop an evidence-based guidance for the installation of ACE-inhibitor therapy. Obviously, therapy should only be applied in those patients who most likely will benefit. Attempts to develop such treatment guidance by using clinical characteristics have been unsuccessful. No heterogeneity in risk reduction by ACE inhibitors has been observed in relation to relevant clinical characteristics. A new approach to such ‘guided-therapy’ could be to integrate more patient-specific characteristics such as the patients’ genetic information. If proven feasible, pharmacogenetic profiling could optimise patients’ benefit of treatment and reduce unnecessary treatment of patients. Cardiovascular pharmacogenetic research of ACE inhibitors in coronary artery disease patients is in a formative stage and studies are limited. The PERGENE study is a large pharmacogenetic substudy of the EUROPA trial, aimed to assess the achievability of pharmacogenetic profiling. We provide an overview of the main results of the PERGENE study in terms of the genetic determinants of treatment benefit and blood pressure response. The main results of the PERGENE study show a pharmacogenetic profile related to the treatment benefit of perindopril identifying responders and non-responders to treatment

Forecasting Tunisian type 2 diabetes prevalence to 2027: validation of a simple model.

BACKGROUND: Most projections of type 2 diabetes (T2D) prevalence are simply based on demographic change (i.e. ageing). We developed a model to predict future trends in T2D prevalence in Tunisia, explicitly taking into account trends in major risk factors (obesity and smoking). This could improve assessment of policy options for prevention and health service planning. METHODS: The IMPACT T2D model uses a Markov approach to integrate population, obesity and smoking trends to estimate future T2D prevalence. We developed a model for the Tunisian population from 1997 to 2027, and validated the model outputs by comparing with a subsequent T2D prevalence survey conducted in 2005. RESULTS: The model estimated that the prevalence of T2D among Tunisians aged over 25 years was 12.0% in 1997 (95% confidence intervals 9.6%-14.4%), increasing to 15.1% (12.5%-17.4%) in 2005. Between 1997 and 2005, observed prevalence in men increased from 13.5% to 16.1% and in women from 12.9% to 14.1%. The model forecast for a dramatic rise in prevalence by 2027 (26.6% overall, 28.6% in men and 24.7% in women). However, if obesity prevalence declined by 20% in the 10 years from 2013, and if smoking decreased by 20% over 10 years from 2009, a 3.3% reduction in T2D prevalence could be achieved in 2027 (2.5% in men and 4.1% in women). CONCLUSIONS: This innovative model provides a reasonably close estimate of T2D prevalence for Tunisia over the 1997-2027 period. Diabetes burden is now a significant public health challenge. Our model predicts that this burden will increase significantly in the next two decades. Tackling obesity, smoking and other T2D risk factors thus needs urgent action. Tunisian decision makers have therefore defined two strategies: obesity reduction and tobacco control. Responses will be evaluated in future population surveys

Heralded quantum entanglement between two crystals

Quantum networks require the crucial ability to entangle quantum nodes. A prominent example is the quantum repeater which allows overcoming the distance barrier of direct transmission of single photons, provided remote quantum memories can be entangled in a heralded fashion. Here we report the observation of heralded entanglement between two ensembles of rare-earth-ions doped into separate crystals. A heralded single photon is sent through a 50/50 beamsplitter, creating a single-photon entangled state delocalized between two spatial modes. The quantum state of each mode is subsequently mapped onto a crystal, leading to an entangled state consisting of a single collective excitation delocalized between two crystals. This entanglement is revealed by mapping it back to optical modes and by estimating the concurrence of the retrieved light state. Our results highlight the potential of rare-earth-ions doped crystals for entangled quantum nodes and bring quantum networks based on solid-state resources one step closer.Comment: 10 pages, 5 figure

A cooperative instinct

Acting on a gut feeling may sometimes lead to poor decisions, but it will usually support the common good, according to a study showing that human intuition favours cooperative, rather than selfish, behaviour