Genetic partitioning of interleukin-6 signalling in mice dissociates Stat3 from Smad3-mediated lung fibrosis

Idiopathic pulmonary fibrosis (IPF) is a fatal disease that is unresponsive to current therapies and characterized by excessive collagen deposition and subsequent fibrosis. While inflammatory cytokines, including interleukin (IL)-6, are elevated in IPF, the molecular mechanisms that underlie this disease are incompletely understood, although the development of fibrosis is believed to depend on canonical transforming growth factor (TGF)-β signalling. We examined bleomycin-induced inflammation and fibrosis in mice carrying a mutation in the shared IL-6 family receptor gp130. Using genetic complementation, we directly correlate the extent of IL-6-mediated, excessive Stat3 activity with inflammatory infiltrates in the lung and the severity of fibrosis in corresponding gp130757F mice. The extent of fibrosis was attenuated in B lymphocyte-deficient gp130757F;µMT−/− compound mutant mice, but fibrosis still occurred in their Smad3−/− counterparts consistent with the capacity of excessive Stat3 activity to induce collagen 1α1 gene transcription independently of canonical TGF-β/Smad3 signalling. These findings are of therapeutic relevance, since we confirmed abundant STAT3 activation in fibrotic lungs from IPF patients and showed that genetic reduction of Stat3 protected mice from bleomycin-induced lung fibrosis

Improving adherence to acute low back pain guideline recommendations with chiropractors and physiotherapists: the ALIGN cluster randomised controlled trial

Background Acute low back pain is a common condition, has high burden, and there are evidence-to-practice gaps in the chiropractic and physiotherapy setting for imaging and giving advice to stay active. The aim of this cluster randomised trial was to estimate the effects of a theory- and evidence-based implementation intervention to increase chiropractors’ and physiotherapists’ adherence to a guideline for acute low back pain compared with the comparator (passive dissemination of the guideline). In particular, the primary aim of the intervention was to reduce inappropriate imaging referral and improve patient low back pain outcomes, and to determine whether this intervention was cost-effective. Methods Physiotherapy and chiropractic practices in the state of Victoria, Australia, comprising at least one practising clinician who provided care to patients with acute low back pain, were invited to participate. Patients attending these practices were included if they had acute non-specific low back pain (duration less than 3 months), were 18 years of age or older, and were able to understand and read English. Practices were randomly assigned either to a tailored, multi-faceted intervention based on the guideline (interactive educational symposium plus academic detailing) or passive dissemination of the guideline (comparator). A statistician independent of the study team undertook stratified randomisation using computer-generated random numbers; four strata were defined by professional group and the rural or metropolitan location of the practice. Investigators not involved in intervention delivery were blinded to allocation. Primary outcomes were X-ray referral self-reported by clinicians using a checklist and patient low back pain-specific disability (at 3 months). Results A total of 104 practices (43 chiropractors, 85 physiotherapists; 755 patients) were assigned to the intervention and 106 practices (45 chiropractors, 97 physiotherapists; 603 patients) to the comparator; 449 patients were available for the patient-level primary outcome. There was no important difference in the odds of patients being referred for X-ray (adjusted (Adj) OR: 1.40; 95% CI 0.51, 3.87; Adj risk difference (RD): 0.01; 95% CI − 0.02, 0.04) or patient low back pain-specific disability (Adj mean difference: 0.37; 95% CI − 0.48, 1.21, scale 0–24). The intervention did lead to improvement for some key secondary outcomes, including giving advice to stay active (Adj OR: 1.96; 95% CI 1.20, 3.22; Adj RD: 0.10; 95% CI 0.01, 0.19) and intending to adhere to the guideline recommendations (e.g. intention to refer for X-ray: Adj OR: 0.27; 95% CI 0.17, 0.44; intention to give advice to stay active: Adj OR: 2.37; 95% CI 1.51, 3.74). Conclusions Intervention group clinicians were more likely to give advice to stay active and to intend to adhere to the guideline recommendations about X-ray referral. The intervention did not change the primary study outcomes, with no important differences in X-ray referral and patient disability between groups, implying that hypothesised reductions in health service utilisation and/or productivity gains are unlikely to offset the direct costs of the intervention. We report these results with the caveat that we enrolled less patients into the trial than our determined sample size. We cannot recommend this intervention as a cost-effective use of resources

Giant positive magnetoresistance in metallic VOx thin films

We report on giant positive magnetoresistance effect observed in VOx thin films, epitaxially grown on SrTiO3 substrate. The MR effect depends strongly on temperature and oxygen content and is anisotropic. At low temperatures its magnitude reaches 70% in a magnetic field of 5 T. Strong electron-electron interactions in the presence of strong disorder may qualitatively explain the results. An alternative explanation, related to a possible magnetic instability, is also discussed.Comment: 4 pages, 5 figures included in the text, references update

Implementing evidence-based recommended practices for the management of patients with mild traumatic brain injuries in Australian emergency care departments: study protocol for a cluster randomised controlled trial

Background: Mild head injuries commonly present to emergency departments. The challenges facing clinicians in emergency departments include identifying which patients have traumatic brain injury, and which patients can safely be sent home. Traumatic brain injuries may exist with subtle symptoms or signs, but can still lead to adverse outcomes. Despite the existence of several high quality clinical practice guidelines, internationally and in Australia, research shows inconsistent implementation of these recommendations. The aim of this trial is to test the effectiveness of a targeted, theory- and evidence-informed implementation intervention to increase the uptake of three key clinical recommendations regarding the emergency department management of adult patients (18 years of age or older) who present following mild head injuries (concussion), compared with passive dissemination of these recommendations. The primary objective is to establish whether the intervention is effective in increasing the percentage of patients for which appropriate post-traumatic amnesia screening is performed. Methods/design: The design of this study is a cluster randomised trial. We aim to include 34 Australian 24-hour emergency departments, which will be randomised to an intervention or control group. Control group departments will receive a copy of the most recent Australian evidence-based clinical practice guideline on the acute management of patients with mild head injuries. The intervention group will receive an implementation intervention based on an analysis of influencing factors, which include local stakeholder meetings, identification of nursing and medical opinion leaders in each site, a train-the-trainer day and standardised education and interactive workshops delivered by the opinion leaders during a 3 month period of time. Clinical practice outcomes will be collected retrospectively from medical records by independent chart auditors over the 2 month period following intervention delivery (patient level outcomes). In consenting hospitals, eligible patients will be recruited for a follow-up telephone interview conducted by trained researchers. A cost-effectiveness analysis and process evaluation using mixed-methods will be conducted. Sample size calculations are based on including 30 patients on average per department. Outcome assessors will be blinded to group allocation

Predictors of premature termination from psychotherapy for anorexia nervosa: Low treatment credibility, early therapy alliance, and self-transcendence

Objective: Failure to complete treatment for anorexia nervosa (AN) is- common, clinically concerning but difficult to predict. This study examines whether therapy-related factors (patient-rated pretreatment credibility and early therapeutic alliance) predict subsequent premature termination of treatment (PTT) alongside self-transcendence (a previously identified clinical predictor) in women with AN. Methods: 56 women aged 17–40 years participating in a randomized outpatient psychotherapy trial for AN. Treatment completion was defined as attending 15/20 planned sessions. Measures were the Treatment Credibility, Temperament and Character Inventory, Vanderbilt Therapeutic Alliance Scale and the Vanderbilt Psychotherapy Process Scale. Statistics were univariate tests, correlations, and logistic regression. Results: Treatment credibility and certain early patient and therapist alliance/process subscales predicted PTT. Lower self-transcendence and lower early process accounted for 33% of the variance in predicting PTT. Discussion: Routine assessment of treatment credibility and early process (comprehensively assessed from multiple perspectives) may help clinicians reduce PTT thereby enhancing treatment outcomes

A Quantitative Model of Energy Release and Heating by Time-dependent, Localized Reconnection in a Flare with a Thermal Loop-top X-ray Source

We present a quantitative model of the magnetic energy stored and then released through magnetic reconnection for a flare on 26 Feb 2004. This flare, well observed by RHESSI and TRACE, shows evidence of non-thermal electrons only for a brief, early phase. Throughout the main period of energy release there is a super-hot (T>30 MK) plasma emitting thermal bremsstrahlung atop the flare loops. Our model describes the heating and compression of such a source by localized, transient magnetic reconnection. It is a three-dimensional generalization of the Petschek model whereby Alfven-speed retraction following reconnection drives supersonic inflows parallel to the field lines, which form shocks heating, compressing, and confining a loop-top plasma plug. The confining inflows provide longer life than a freely-expanding or conductively-cooling plasma of similar size and temperature. Superposition of successive transient episodes of localized reconnection across a current sheet produces an apparently persistent, localized source of high-temperature emission. The temperature of the source decreases smoothly on a time scale consistent with observations, far longer than the cooling time of a single plug. Built from a disordered collection of small plugs, the source need not have the coherent jet-like structure predicted by steady-state reconnection models. This new model predicts temperatures and emission measure consistent with the observations of 26 Feb 2004. Furthermore, the total energy released by the flare is found to be roughly consistent with that predicted by the model. Only a small fraction of the energy released appears in the super-hot source at any one time, but roughly a quarter of the flare energy is thermalized by the reconnection shocks over the course of the flare. All energy is presumed to ultimately appear in the lower-temperature T<20 MK, post-flare loops

3D MHD Flux Emergence Experiments: Idealized models and coronal interactions

This paper reviews some of the many 3D numerical experiments of the emergence of magnetic fields from the solar interior and the subsequent interaction with the pre-existing coronal magnetic field. The models described here are idealized, in the sense that the internal energy equation only involves the adiabatic, Ohmic and viscous shock heating terms. However, provided the main aim is to investigate the dynamical evolution, this is adequate. Many interesting observational phenomena are explained by these models in a self-consistent manner.Comment: Review article, accepted for publication in Solar Physic

Charge ordering and antiferromagnetic exchange in layered molecular crystals of the theta type

We consider the electronic properties of layered molecular crystals of the type theta-D$_2$A, where A is an anion and D is a donor molecule such as BEDT-TTF [where BEDT-TTF is bis-(ethylenedithia-tetrathiafulvalene)] which is arranged in the theta type pattern within the layers. We argue that the simplest strongly correlated electron model that can describe the rich phase diagram of these materials is the extended Hubbard model on the square lattice at a quarter filling. In the limit where the Coulomb repulsion on a single site is large, the nearest-neighbour Coulomb repulsion, V, plays a crucial role. When V is much larger than the intermolecular hopping integral t the ground state is an insulator with charge ordering. In this phase antiferromagnetism arises due to a novel fourth-order superexchange process around a plaquette on the square lattice. We argue that the charge ordered phase is destroyed below a critical non-zero value V, of the order of t. Slave boson theory is used to explicitly demonstrate this for the SU(N) generalisation of the model, in the large N limit. We also discuss the relevance of the model to the all-organic family beta''-(BEDT-TTF)$_2$SF$_5$YSO$_3$ where Y = CH$_2$CF$_2$, CH$_2$, CHF.Comment: 15 pages, 6 eps figure

A Precious Bequest: Contemporary Research with the WPA-CCC Collections from Moundville, Alabama *

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72459/1/j.1749-6632.1981.tb28184.x.pd

Origins of the Ambient Solar Wind: Implications for Space Weather

The Sun's outer atmosphere is heated to temperatures of millions of degrees, and solar plasma flows out into interplanetary space at supersonic speeds. This paper reviews our current understanding of these interrelated problems: coronal heating and the acceleration of the ambient solar wind. We also discuss where the community stands in its ability to forecast how variations in the solar wind (i.e., fast and slow wind streams) impact the Earth. Although the last few decades have seen significant progress in observations and modeling, we still do not have a complete understanding of the relevant physical processes, nor do we have a quantitatively precise census of which coronal structures contribute to specific types of solar wind. Fast streams are known to be connected to the central regions of large coronal holes. Slow streams, however, appear to come from a wide range of sources, including streamers, pseudostreamers, coronal loops, active regions, and coronal hole boundaries. Complicating our understanding even more is the fact that processes such as turbulence, stream-stream interactions, and Coulomb collisions can make it difficult to unambiguously map a parcel measured at 1 AU back down to its coronal source. We also review recent progress -- in theoretical modeling, observational data analysis, and forecasting techniques that sit at the interface between data and theory -- that gives us hope that the above problems are indeed solvable.Comment: Accepted for publication in Space Science Reviews. Special issue connected with a 2016 ISSI workshop on "The Scientific Foundations of Space Weather." 44 pages, 9 figure