Psychological interventions are a mainstay of modern pain management practice and a recommended feature of a modern pain treatment service. Systematic reviews for the evidence of psychological ...interventions are reviewed in this article. The evidence for effectiveness is strongest for cognitive behavioural therapy with a focus on cognitive coping strategies and behavioural rehearsal. Most evidence is available for treatments of adult pain, although adolescent chronic pain treatments are also reviewed. It is clear that treatment benefit can be achieved with cognitive behavioural methods. It is possible to effect change in pain, mood, and disability, changes not achieved by chance or by exposure to any other treatment. However, the overall effect sizes of treatments for adults, across all trials, are modest. Reasons for the relatively modest treatment effects are discussed within the context of all treatments for chronic pain being disappointing when measured by the average. Suggestions for improving both trials and evidence summaries are made. Finally, consideration is given to what can be achieved by the pain specialist without access to specialist psychology resource.
Summary
Background
The Harmonising Outcome Measures for Eczema (HOME) initiative has defined four core outcome domains for a core outcome set (COS) to be measured in all atopic eczema (AE) trials to ...ensure cross‐trial comparison: clinical signs, symptoms, quality of life and long‐term control.
Objectives
The aim of this paper is to report on the consensus process that was used to select the core instrument to consistently assess symptoms in all future AE trials.
Methods
Following the HOME roadmap, two systematic reviews were performed which identified three instruments that had sufficient evidence of validity, reliability and feasibility to be considered for the final COS.
Results
At the fourth international HOME meeting, there was broad consensus among all stakeholders that the Patient‐Oriented Eczema Measure (POEM) should be used as the core instrument (87·5% agreed, 9·4% unsure, 3·1% disagreed).
Conclusions
All relevant stakeholders are encouraged to use POEM as the chosen instrument to measure the core domain of symptoms in all future AE clinical trials. Other instruments of interest can be used in addition to POEM.
What's already known about this topic?
There is insufficient high‐quality evidence for many of the treatments of atopic eczema (AE), which is partly due to the heterogeneity in outcomes used in clinical trials.
The Harmonising Outcome Measures for Eczema initiative defined ‘symptoms’ as one of the core outcome domains that should be measured in AE clinical trials.
What does this study add?
Consensus was reached on the Patient‐Oriented Eczema Measure (POEM) as the core instrument to measure symptoms.
This statement should promote awareness among all stakeholders.
What are the clinical implications of this work?
Not only itch and sleeplessness are symptoms important for patients with AE.
All relevant stakeholders are encouraged to use POEM as the chosen instrument to measure the core domain of symptoms in all future AE clinical trials.
Respond to this article
Linked Comment: Naldi. Br J Dermatol 2017; 176:852–853
Plain language summary available online
Summary
Background
Anti‐tumour necrosis factor‐α (TNFα) antibodies are efficacious in inflammatory bowel disease (IBD). These drugs carry the theoretical risk of malignancy, particularly lymphoma, ...but no systematic review and meta‐analysis has examined this issue.
Aim
To pool data from all available placebo‐controlled studies to estimate risk of malignancy with anti‐TNFα therapy in IBD.
Methods
MEDLINE, EMBASE and the Cochrane central register of controlled trials were searched to November 2013. Randomised controlled trials (RCTs) comparing anti‐TNFα therapy with placebo in adults with Crohn's disease (CD) or ulcerative colitis (UC) were eligible. Data were pooled to obtain a relative risk (RR) of malignancy with a 95% confidence interval (CI).
Results
The search strategy identified 25 338 citations, of which 22 RCTs were eligible (11 infliximab, six adalimumab, four certolizumab and one golimumab) involving 7054 patients (4566 CD and 2488 UC). In total, there were 16 (0.39%) malignancies in 4135 IBD patients allocated to anti‐TNFα, compared with 13 (0.45%) in 2919 patients randomised to placebo. There were no cases of lymphoma in the active treatment group, compared with three (0.1%) in the control group. The RR of malignancy for patients receiving anti‐TNFα therapy compared with placebo was 0.77 (95% CI 0.37–1.59). When seven individuals with nonmelanoma skin cancer were excluded from the analysis, the RR was 0.90 (95% CI 0.40–2.02).
Conclusions
Anti‐TNFα therapy was not associated with an increased risk of malignancy in patients with IBD. However, no trials provided data for risk of malignancy beyond 1 year of treatment, meaning that an increased risk in the longer term cannot be excluded.
Acid mine drainage (AMD) is a widespread environmental problem associated with both working and abandoned mining operations, resulting from the microbial oxidation of pyrite in presence of water and ...air, affording an acidic solution that contains toxic metal ions. The generation of AMD and release of dissolved heavy metals is an important concern facing the mining industry. The present study aimed at evaluating the use of low-cost sorbents like coal fly ash, natural clinker and synthetic zeolites to clean-up AMD generated at the Parys Mountain copper–lead–zinc deposit, Anglesey (North Wales), and to remove heavy metals and ammonium from AMD. pH played a very important role in the sorption/removal of the contaminants and a higher adsorbent ratio in the treatment of AMD promoted the increase of the pH, particularly using natural clinker-based faujasite (7.70–9.43) and the reduction of metal concentration. Na-phillipsite showed a lower efficiency as compared to that of faujasite. Selectivity of faujasite for metal removal was, in decreasing order, Fe
>
As
>
Pb
>
Zn
>
Cu
>
Ni
>
Cr. Based on these results, the use of these materials has the potential to provide improved methods for the treatment of AMD.
Leucine-rich repeat-containing G-protein coupled receptor (LGR5 or GPR49) potentiates canonical Wnt/β-catenin signalling and is a marker of normal stem cells in several tissues, including the ...intestine. Consistent with stem cell potential, single isolated LGR5
cells from the gut generate self-organising crypt/villus structures in vitro termed organoids or 'mini-guts', which accurately model the parent tissue. The well characterised deregulation of Wnt/β-catenin signalling that occurs during the adenoma-carcinoma sequence in colorectal cancer (CRC) renders LGR5 an interesting therapeutic target. Furthermore, recent studies demonstrating that CRC tumours contain LGR5
subsets and retain a degree of normal tissue architecture has heightened translational interest. Such reports fuel hope that specific subpopulations or molecules within a tumour may be therapeutically targeted to prevent relapse and induce long-term remissions. Despite these observations, many studies within this field have produced conflicting and confusing results with no clear consensus on the therapeutic value of LGR5. This review will recap the various oncogenic and tumour suppressive roles that have been described for the LGR5 molecule in CRC. It will further highlight recent studies indicating the plasticity or redundancy of LGR5
cells in intestinal cancer progression and assess the overall merit of therapeutically targeting LGR5 in CRC.
Cryovolcanism on Ceres Ruesch, O.; Platz, T.; Schenk, P. ...
Science (American Association for the Advancement of Science),
09/2016, Letnik:
353, Številka:
6303
Journal Article
Recenzirano
Odprti dostop
Volcanic edifices are abundant on rocky bodies of the inner solar system. In the cold outer solar system, volcanism can occur on solid bodies with a water-ice shell, but derived cryovolcanic ...constructs have proved elusive. We report the discovery, using Dawn Framing Camera images, of a landform on dwarf planet Ceres that we argue represents a viscous cryovolcanic dome. Parent material of the cryomagma is a mixture of secondary minerals, including salts and water ice. Absolute model ages from impact craters reveal that extrusion of the dome has occurred recently. Ceres' evolution must have been able to sustain recent interior activity and associated surface expressions. We propose salts with low eutectic temperatures and thermal conductivities as key drivers for Ceres' long-term internal evolution.
starbench: the D-type expansion of an H ii region Bisbas, T. G; Haworth, T. J; Williams, R. J. R ...
Monthly notices of the Royal Astronomical Society,
10/2015, Letnik:
453, Številka:
2
Journal Article
Recenzirano
Odprti dostop
starbench is a project focused on benchmarking and validating different star formation and stellar feedback codes. In this first starbench paper we perform a comparison study of the D-type expansion ...of an H ii region. The aim of this work is to understand the differences observed between the 12 participating numerical codes against the various analytical expressions examining the D-type phase of H ii region expansion. To do this, we propose two well-defined tests which are tackled by 1D and 3D grid- and smoothed particle hydrodynamics-based codes. The first test examines the ‘early phase’ D-type scenario during which the mechanical pressure driving the expansion is significantly larger than the thermal pressure of the neutral medium. The second test examines the ‘late phase’ D-type scenario during which the system relaxes to pressure equilibrium with the external medium. Although they are mutually in excellent agreement, all 12 participating codes follow a modified expansion law that deviates significantly from the classical Spitzer solution in both scenarios. We present a semi-empirical formula combining the two different solutions appropriate to both early and late phases that agrees with high-resolution simulations to ≲ 2 per cent. This formula provides a much better benchmark solution for code validation than the Spitzer solution. The present comparison has validated the participating codes and through this project we provide a data set for calibrating the treatment of ionizing radiation hydrodynamics codes.
The diverse leukocyte infiltrate in atherosclerotic mouse aortas was recently analyzed in 9 single-cell RNA sequencing and 2 mass cytometry studies. In a comprehensive meta-analysis, we confirm 4 ...known macrophage subsets—resident, inflammatory, interferon-inducible cell, and Trem2 (triggering receptor expressed on myeloid cells-2) foamy macrophages—and identify a new macrophage subset resembling cavity macrophages. We also find that monocytes, neutrophils, dendritic cells, natural killer cells, innate lymphoid cells-2, and CD (cluster of differentiation)-8 T cells form prominent and separate immune cell populations in atherosclerotic aortas. Many CD4 T cells express IL (interleukin)-17 and the chemokine receptor CXCR (C-X-C chemokine receptor)-6. A small number of regulatory T cells and T helper 1 cells is also identified. Immature and naive T cells are present in both healthy and atherosclerotic aortas. Our meta-analysis overcomes limitations of individual studies that, because of their experimental approach, over- or underrepresent certain cell populations. Mass cytometry studies demonstrate that cell surface phenotype provides valuable information beyond the cell transcriptomes. The present analysis helps resolve some long-standing controversies in the field. First, Trem2 foamy macrophages are not proinflammatory but interferon-inducible cell and inflammatory macrophages are. Second, about half of all foam cells are smooth muscle cell-derived, retaining smooth muscle cell transcripts rather than transdifferentiating to macrophages. Third, Pf4, which had been considered specific for platelets and megakaryocytes, is also prominently expressed in the main population of resident vascular macrophages. Fourth, a new type of resident macrophage shares transcripts with cavity macrophages. Finally, the discovery of a prominent innate lymphoid cell-2 cluster links the single-cell RNA sequencing work to recent flow cytometry data suggesting a strong atheroprotective role of innate lymphoid cells-2. This resolves apparent discrepancies regarding the role of T helper 2 cells in atherosclerosis based on studies that predated the discovery of innate lymphoid cells-2 cells.
Enzymes catalysing the methylation of the 5-position of cytosine (mC) have essential roles in regulating gene expression and maintaining cellular identity. Recently, TET1 was found to hydroxylate the ...methyl group of mC, converting it to 5-hydroxymethyl cytosine (hmC). Here we show that TET1 binds throughout the genome of embryonic stem cells, with the majority of binding sites located at transcription start sites (TSSs) of CpG-rich promoters and within genes. The hmC modification is found in gene bodies and in contrast to mC is also enriched at CpG-rich TSSs. We provide evidence further that TET1 has a role in transcriptional repression. TET1 binds a significant proportion of Polycomb group target genes. Furthermore, TET1 associates and colocalizes with the SIN3A co-repressor complex. We propose that TET1 fine-tunes transcription, opposes aberrant DNA methylation at CpG-rich sequences and thereby contributes to the regulation of DNA methylation fidelity.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The geomorphology of Ceres Buczkowski, D. L.; Schmidt, B. E.; Williams, D. A. ...
Science (American Association for the Advancement of Science),
09/2016, Letnik:
353, Številka:
6303
Journal Article
Recenzirano
Odprti dostop
Analysis of Dawn spacecraft Framing Camera image data allows evaluation of the topography and geomorphology of features on the surface of Ceres. The dwarf planet is dominated by numerous craters, but ...other features are also common. Linear structures include both those associated with impact craters and those that do not appear to have any correlation to an impact event. Abundant lobate flows are identified, and numerous domical features are found at a range of scales. Features suggestive of near-surface ice, cryomagmatism, and cryovolcanism have been identified. Although spectroscopic analysis has currently detected surface water ice at only one location on Ceres, the identification of these potentially ice-related features suggests that there may be at least some ice in localized regions in the crust.
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