Showing papers by "University of Leicester published in 2005"

Classification of cell death: recommendations of the Nomenclature Committee on Cell Death

Abstract: Different types of cell death are often defined by morphological criteria, without a clear reference to precise biochemical mechanisms. The Nomenclature Committee on Cell Death (NCCD) proposes unified criteria for the definition of cell death and of its different morphologies, while formulating several caveats against the misuse of words and concepts that slow down progress in the area of cell death research. Authors, reviewers and editors of scientific periodicals are invited to abandon expressions like 'percentage apoptosis' and to replace them with more accurate descriptions of the biochemical and cellular parameters that are actually measured. Moreover, at the present stage, it should be accepted that caspase-independent mechanisms can cooperate with (or substitute for) caspases in the execution of lethal signaling pathways and that 'autophagic cell death' is a type of cell death occurring together with (but not necessarily by) autophagic vacuolization. This study details the 2009 recommendations of the NCCD on the use of cell death-related terminology including 'entosis', 'mitotic catastrophe', 'necrosis', 'necroptosis' and 'pyroptosis'.

The Swift X-ray telescope

Abstract: he Swift Gamma-Ray Explorer is designed to make prompt multiwavelength observations of gamma-ray bursts (GRBs) and GRB afterglows. The X-ray telescope (XRT) enables Swift to determine GRB positions with a few arcseconds accuracy within 100 s of the burst onset. The XRT utilizes a mirror set built for JET-X and an XMM-Newton/EPIC MOS CCD detector to provide a sensitive broad-band (0.2–10 keV) X-ray imager with effective area of > 120 cm2 at 1.5 keV, field of view of 23.6 × 23.6 arcminutes, and angular resolution of 18 arcseconds (HPD). The detection sensitivity is 2×10−14 erg cm−2 s−1 in 104 s. The instrument is designed to provide automated source detection and position reporting within 5 s of target acquisition. It can also measure the redshifts of GRBs with Fe line emission or other spectral features. The XRT operates in an auto-exposure mode, adjusting the CCD readout mode automatically to optimize the science return for each frame as the source intensity fades. The XRT will measure spectra and lightcurves of the GRB afterglow beginning about a minute after the burst and will follow each burst for days or weeks.

Synthesising qualitative and quantitative evidence: A review of possible methods:

Abstract: BackgroundThe limitations of traditional forms of systematic review in making optimal use of all forms of evidence are increasingly evident, especially for policy-makers and practitioners. There is...

The cornified envelope: a model of cell death in the skin

Abstract: The epidermis functions as a barrier against the environment by means of several layers of terminally differentiated, dead keratinocytes - the cornified layer, which forms the endpoint of epidermal differentiation and death. The cornified envelope replaces the plasma membrane of differentiating keratinocytes and consists of keratins that are enclosed within an insoluble amalgam of proteins, which are crosslinked by transglutaminases and surrounded by a lipid envelope. New insights into the molecular mechanisms and the physiological endpoints of cornification are increasing our understanding of the pathological defects of this unique form of programmed cell death, which is associated with barrier malfunctions and ichthyosis.

Cdx2 is required for correct cell fate specification and differentiation of trophectoderm in the mouse blastocyst

Abstract: Blastocyst formation marks the segregation of the first two cell lineages in the mammalian preimplantation embryo: the inner cell mass (ICM) that will form the embryo proper and the trophectoderm (TE) that gives rise to the trophoblast lineage. Commitment to ICM lineage is attributed to the function of the two transcription factors, Oct4 (encoded by Pou5f1) and Nanog. However, a positive regulator of TE cell fate has not been described. The T-box protein eomesodermin (Eomes) and the caudal-type homeodomain protein Cdx2 are expressed in the TE, and both Eomes and Cdx2 homozygous mutant embryos die around the time of implantation. A block in early TE differentiation occurs in Eomes mutant blastocysts. However, Eomes mutant blastocysts implant, and Cdx2 and Oct4 expression are correctly restricted to the ICM TE. Blastocoel formation initiates in Cdx2 mutants but epithelial integrity is not maintained and embryos fail to implant. Loss of Cdx2 results in failure to downregulate Oct4 and Nanog in outer cells of the blastocyst and subsequent death of those cells. Thus, Cdx2 is essential for segregation of the ICM and TE lineages at the blastocyst stage by ensuring repression of Oct4 and Nanog in the TE.

Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumours (NETs)

Abstract: These guidelines update previous guidance published in 2005. They have been revised by a group who are members of the UK and Ireland Neuroendocrine Tumour Society with endorsement from the clinical committees of the British Society of Gastroenterology, the Society for Endocrinology, the Association of Surgeons of Great Britain and Ireland (and its Surgical Specialty Associations), the British Society of Gastrointestinal and Abdominal Radiology and others. The authorship represents leaders of the various groups in the UK and Ireland Neuroendocrine Tumour Society, but a large amount of work has been carried out by other specialists, many of whom attended a guidelines conference in May 2009. We have attempted to represent this work in the acknowledgements section. Over the past few years, there have been advances in the management of neuroendocrine tumours, which have included clearer characterisation, more specific and therapeutically relevant diagnosis, and improved treatments. However, there remain few randomised trials in the field and the disease is uncommon, hence all evidence must be considered weak in comparison with other more common cancers.

Resolved Massive Star Clusters in the Milky Way and Its Satellites: Brightness Profiles and a Catalog of Fundamental Parameters

Abstract: We present a database of structural and dynamical properties for 153 spatially resolved star clusters in the Milky Way, the Large and Small Magellanic Clouds, and the Fornax dwarf spheroidal. This database complements and extends others in the literature, such as those of Harris and Mackey & Gilmore. Our cluster sample comprises 50 "young massive clusters" in the LMC and SMC, and 103 old globular clusters between the four galaxies. The parameters we list include central and half-light-averaged surface brightnesses and mass densities; core and effective radii; central potentials, concentration parameters, and tidal radii; predicted central velocity dispersions and escape velocities; total luminosities, masses, and binding energies; central phase-space densities; half-mass relaxation times; and "κ-space" parameters. We use publicly available population-synthesis models to compute stellar-population properties (intrinsic B - V colors, reddenings, and V-band mass-to-light ratios) for the same 153 clusters plus another 63 globulars in the Milky Way. We also take velocity-dispersion measurements from the literature for a subset of 57 (mostly old) clusters to derive dynamical mass-to-light ratios for them, showing that these compare very well to the population-synthesis predictions. The combined data set is intended to serve as the basis for future investigations of structural correlations and the fundamental plane of massive star clusters, including especially comparisons between the systemic properties of young and old clusters. The structural and dynamical parameters are derived from fitting three different models—the modified isothermal sphere of King; an alternate modified isothermal sphere based on the ad hoc stellar distribution function of Wilson; and asymptotic power-law models with constant-density cores—to the surface-brightness profile of each cluster. Surface-brightness data for the LMC, SMC, and Fornax clusters are based in large part on the work of Mackey & Gilmore, but include significant supplementary data culled from the literature and important corrections to Mackey & Gilmore's V-band magnitude scale. The profiles of Galactic globular clusters are taken from Trager et al. We address the question of which model fits each cluster best, finding in the majority of cases that the Wilson models—which are spatially more extended than King models but still include a finite, "tidal" cutoff in density—fit clusters of any age, in any galaxy, as well as or better than King models. Untruncated, asymptotic power laws often fit about as well as Wilson models but can be significantly worse. We argue that the extended halos known to characterize many Magellanic Cloud clusters may be examples of the generic envelope structure of self-gravitating star clusters, not just transient features associated strictly with young age.

Positive Adjustment to Threatening Events: An Organismic Valuing Theory of Growth through Adversity:

Abstract: A positive psychological theory of growth through adversity is proposed. The organismic valuing theory of growth through adversity posits an intrinsic motivation toward growth, showing how this lea...

Models of giant planet formation with migration and disc evolution

Abstract: We present a new model of giant planet formation that extends the core-accretion model of Pollack et al. (1996, Icarus, 124, 62) to include migration, disc evolution and gap formation. We show that taking these effects into account can lead to much more rapid formation of giant planets, making it compatible with the typical disc lifetimes inferred from observations of young circumstellar discs. This speed up is due to the fact that migration prevents the severe depletion of the feeding zone as observed in in situ calculations. Hence, the growing planet is never isolated and it can reach cross-over mass on a much shorter timescale. To illustrate the range of planets that can form in our model, we describe a set of simulations in which we have varied some of the initial parameters and compare the final masses and semi-major axes with those inferred from observed extra-solar planets.

Epidemiology of injuries in English professional rugby union: part 1 match injuries

Abstract: Objectives: To undertake a detailed, large scale epidemiological study of match injuries sustained by professional rugby union players in order to define their incidence, nature, severity, and causes. Methods: A two season prospective design was used to study match injuries associated with 546 rugby union players at 12 English Premiership clubs. Team clinicians reported all match injuries on a weekly basis and provided details of the location, diagnosis, severity, and mechanism of each injury. Match exposures for individual players were recorded on a weekly basis. Loss of time from training and match play was used as the definition of an injury. Results: The overall incidence of injury was 91 injuries/1000 player-hours, and each injury resulted on average in 18 days lost time. Recurrences, which accounted for 18% of injuries, were significantly more severe (27 days) than new injuries (16 days). Thigh haematomas were the most common injury for forwards and backs, but anterior cruciate ligament injuries for forwards and hamstring injuries for backs caused the greatest number of days absence. Contact mechanisms accounted for 72% of injuries, but foul play was only implicated in 6% of injuries. The ruck and maul elements of the game caused most injuries to forwards, and being tackled caused most injuries to backs. The hooker and outside centre were the playing positions at greatest risk of injury. Conclusions: On average, a club will have 18% of their players unavailable for selection as a consequence of match injuries.

Adjusting for treatment effects in studies of quantitative traits: antihypertensive therapy and systolic blood pressure.

Abstract: A population-based study of a quantitative trait may be seriously compromised when the trait is subject to the effects of a treatment. For example, in a typical study of quantitative blood pressure (BP) 15 per cent or more of middle-aged subjects may take antihypertensive treatment. Without appropriate correction, this can lead to substantial shrinkage in the estimated effect of aetiological determinants of scientific interest and a marked reduction in statistical power. Correction relies upon imputation, in treated subjects, of the underlying BP from the observed BP having invoked one or more assumptions about the bioclinical setting. There is a range of different assumptions that may be made, and a number of different analytical models that may be used. In this paper, we motivate an approach based on a censored normal regression model and compare it with a range of other methods that are currently used or advocated. We compare these methods in simulated data sets and assess the estimation bias and the loss of power that ensue when treatment effects are not appropriately addressed. We also apply the same methods to real data and demonstrate a pattern of behaviour that is consistent with that in the simulation studies. Although all approaches to analysis are necessarily approximations, we conclude that two of the adjustment methods appear to perform well across a range of realistic settings. These are: (1) the addition of a sensible constant to the observed BP in treated subjects; and (2) the censored normal regression model. A third, non-parametric, method based on averaging ordered residuals may also be advocated in some settings. On the other hand, three approaches that are used relatively commonly are fundamentally flawed and should not be used at all. These are: (i) ignoring the problem altogether and analysing observed BP in treated subjects as if it was underlying BP; (ii) fitting a conventional regression model with treatment as a binary covariate; and (iii) excluding treated subjects from the analysis. Given that the more effective methods are straightforward to implement, there is no argument for undertaking a flawed analysis that wastes power and results in excessive bias.

Learning as peripheral participation in communities of practice: a reassessment of key concepts in workplace learning

Abstract: This article explores the strengths and weaknesses of Lave and Wenger's concept of 'legitimate peripheral participation' as a means of understanding workplace learning. It draws on recent ESRC-funded research by the authors in contemporary workplace settings in the UK (manufacturing industry and secondary schools) to establish the extent to which Lave and Wenger's theories can adequately illuminate the nature and process of learning at work. The new research presented here, which was located in complex institutional settings, highlights the diverse nature of patterns and forms of participation. Case study evidence is used to identify individual and contextual factors which underpin and illuminate the ways in which employees learn. The paper argues that whilst Lave and Wenger's work continues to provide an important source of theoretical insight and inspiration for research in to learning at work, it has significant limitations. These limitations relate to the application of their perspective to contemporary workplaces in advanced industrial societies and to the institutional environments in which people work. These complex settings play a crucial role in the configuration of opportunities and barriers to learning that employees encounter.

A short γ-ray burst apparently associated with an elliptical galaxy at redshift z = 0.225

Abstract: Gamma-ray bursts (GRBs) are either ‘long and soft’, or ‘short and hard’. The long-duration type leave a strong afterglow and have been extensively studied. So we have a good idea of what causes them: explosions of massive stars in distant star-forming galaxies. Short GRBs, with no strong afterglow, were harder to pin down. The Swift satellite, launched last November, is designed to study bursts as soon as they happen. Having shown its worth with long GRBs (reported in the 18 August issue of Nature), Swift has now bagged a short burst, GRB 050509B, precisely measured its location and detected the X-ray afterglow. Four papers this week report on this and another recent short burst. Now, over 20 years after they were first recognized, the likely origin of the short GRBs is revealed as a merger between neutron stars of a binary system and the instantaneous production of a black hole. Gamma-ray bursts (GRBs) come in two classes1: long (> 2 s), soft-spectrum bursts and short, hard events. Most progress has been made on understanding the long GRBs, which are typically observed at high redshift (z ≈ 1) and found in subluminous star-forming host galaxies. They are likely to be produced in core-collapse explosions of massive stars2. In contrast, no short GRB had been accurately (< 10″) and rapidly (minutes) located. Here we report the detection of the X-ray afterglow from—and the localization of—the short burst GRB 050509B. Its position on the sky is near a luminous, non-star-forming elliptical galaxy at a redshift of 0.225, which is the location one would expect3,4 if the origin of this GRB is through the merger of neutron-star or black-hole binaries. The X-ray afterglow was weak and faded below the detection limit within a few hours; no optical afterglow was detected to stringent limits, explaining the past difficulty in localizing short GRBs.

Absorptive capacity and productivity spillovers From FDI: a threshold regression analysis

Abstract: This paper explores whether the effect of foreign direct investment (FDI) on productivity growth is dependent on absorptive capacity using recently developed threshold regression techniques. In manufacturing sectors where technology-exploiting multinationals are prevalent, the results point to the presence of nonlinear threshold effects: the productivity benefit from FDI increases with absorptive capacity until some threshold level beyond which it becomes less pronounced. But there is also a minimum absorptive capacity threshold level below which productivity spillovers from FDI are negligible or even negative. On the contrary, no evidence of productivity spillovers is found in sectors where FDI appears to be motivated by technology-sourcing considerations.

Loss of function mutations in the gene encoding Omi/HtrA2 in Parkinson's disease

Abstract: Recently targeted disruption of Omi/HtrA2 has been found to cause neurodegeneration and a parkinsonian phenotype in mice. Using a candidate gene approach, we performed a mutation screening of the Omi/ HtrA2 gene in German Parkinson's disease (PD) patients. In four patients, we identified a novel heterozygous G399S mutation, which was absent in healthy controls. Moreover, we identified a novel A141S polymorphism that was associated with PD (P < 0.05). Both mutations resulted in defective activation of the protease activity of Omi/HtrA2. Immunohistochemistry and functional analysis in stably transfected cells revealed that S399 mutant Omi/HtrA2 and to a lesser extent, the risk allele of the A141S polymorphism induced mitochondrial dysfunction associated with altered mitochondrial morphology. Cells overexpressing S399 mutant Omi/ HtrA2 were more susceptible to stress-induced cell death than wild-type. On the basis of functional genomics, our results provide a novel link between mitochondrial dysfunction and neurodegeneration in PD.

The AUXIN RESPONSE FACTOR 2 gene of Arabidopsis links auxin signalling, cell division, and the size of seeds and other organs

Abstract: Control of seed size involves complex interactions among the zygotic embryo and endosperm, the maternally derived seed coat, and the parent plant. Here we describe a mutant in Arabidopsis, megaintegumenta (mnt), in which seed size and weight are dramatically increased. One factor in this is extra cell division in the integuments surrounding mnt mutant ovules, leading to the formation of enlarged seed coats. Unusually for integument mutants, mnt does not impair female fertility. The mnt lesion also has pleiotropic effects on vegetative and floral development, causing extra cell division and expansion in many organs. mnt was identified as a mutant allele of AUXIN RESPONSE FACTOR 2 (ARF2), a member of a family of transcription factors that mediate gene expression in response to auxin. The mutant phenotype and gene expression studies described here provide evidence that MNT/ARF2 is a repressor of cell division and organ growth. The mutant phenotype also illustrates the importance of growth of the ovule before fertilization in determining final size of the seed.

SIP1/ZEB2 induces EMT by repressing genes of different epithelial cell–cell junctions

Abstract: SIP1/ZEB2 is a member of the δEF-1 family of two-handed zinc finger nuclear factors. The expression of these transcription factors is associated with epithelial mesenchymal transitions (EMT) during development. SIP1 is also expressed in some breast cancer cell lines and was detected in intestinal gastric carcinomas, where its expression is inversely correlated with that of E-cadherin. Here, we show that expression of SIP1 in human epithelial cells results in a clear morphological change from an epithelial to a mesenchymal phenotype. Induction of this epithelial dedifferentiation was accompanied by repression of several cell junctional proteins, with concomitant repression of their mRNA levels. Besides E-cadherin, other genes coding for crucial proteins of tight junctions, desmosomes and gap junctions were found to be transcriptionally regulated by the transcriptional repressor SIP1. Moreover, study of the promoter regions of selected genes by luciferase reporter assays and chromatin immunoprecipitation shows that repression is directly mediated by SIP1. These data indicate that, during epithelial dedifferentiation, SIP1 represses in a coordinated manner the transcription of genes coding for junctional proteins contributing to the dedifferentiated state; this repression occurs by a general mechanism mediated by Smad Interacting Protein 1 (SIP1)-binding sites.

NMDA receptors are expressed in developing oligodendrocyte processes and mediate injury

Abstract: Injury to oligodendrocyte processes, the structures responsible for myelination, is implicated in many forms of brain disorder. Here we show NMDA (N-methyl-D-aspartate) receptor subunit expression on oligodendrocyte processes, and the presence of NMDA receptor subunit messenger RNA in isolated white matter. NR1, NR2A, NR2B, NR2C, NR2D and NR3A subunits showed clustered expression in cell processes, but NR3B was absent. During modelled ischaemia, NMDA receptor activation resulted in rapid Ca2+-dependent detachment and disintegration of oligodendroglial processes in the white matter of mice expressing green fluorescent protein (GFP) specifically in oligodendrocytes (CNP-GFP mice). This effect occurred at mouse ages corresponding to both the initiation and the conclusion of myelination. NR1 subunits were found mainly in oligodendrocyte processes, whereas AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid)/kainate receptor subunits were mainly found in the somata. Consistent with this observation, injury to the somata was prevented by blocking AMPA/kainate receptors, and preventing injury to oligodendroglial processes required the blocking of NMDA receptors. The presence of NMDA receptors in oligodendrocyte processes explains why previous studies that have focused on the somata have not detected a role for NMDA receptors in oligodendrocyte injury. These NMDA receptors bestow a high sensitivity to acute injury and represent an important new target for drug development in a variety of brain disorders.

Simulating Hamiltonian Dynamics

Abstract: Geometric integrators are time-stepping methods, designed such that they exactly satisfy conservation laws, symmetries or symplectic properties of a system of differential equations. In this book the authors outline the principles of geometric integration and demonstrate how they can be applied to provide efficient numerical methods for simulating conservative models. Beginning from basic principles and continuing with discussions regarding the advantageous properties of such schemes, the book introduces methods for the N-body problem, systems with holonomic constraints, and rigid bodies. More advanced topics treated include high-order and variable stepsize methods, schemes for treating problems involving multiple time-scales, and applications to molecular dynamics and partial differential equations. The emphasis is on providing a unified theoretical framework as well as a practical guide for users. The inclusion of examples, background material and exercises enhance the usefulness of the book for self-instruction or as a text for a graduate course on the subject.

How vague is vague? A simulation study of the impact of the use of vague prior distributions in MCMC using WinBUGS.

Abstract: There has been a recent growth in the use of Bayesian methods in medical research. The main reasons for this are the development of computer intensive simulation based methods such as Markov chain Monte Carlo (MCMC), increases in computing power and the introduction of powerful software such as WinBUGS. This has enabled increasingly complex models to be fitted. The ability to fit these complex models has led to MCMC methods being used as a convenient tool by frequentists, who may have no desire to be fully Bayesian. Often researchers want 'the data to dominate' when there is no prior information and thus attempt to use vague prior distributions. However, with small amounts of data the use of vague priors can be problematic. The results are potentially sensitive to the choice of prior distribution. In general there are fewer problems with location parameters. The main problem is with scale parameters. With scale parameters, not only does one have to decide the distributional form of the prior distribution, but also whether to put the prior distribution on the variance, standard deviation or precision. We have conducted a simulation study comparing the effects of 13 different prior distributions for the scale parameter on simulated random effects meta-analysis data. We varied the number of studies (5, 10 and 30) and compared three different between-study variances to give nine different simulation scenarios. One thousand data sets were generated for each scenario and each data set was analysed using the 13 different prior distributions. The frequentist properties of bias and coverage were investigated for the between-study variance and the effect size. The choice of prior distribution was crucial when there were just five studies. There was a large variation in the estimates of the between-study variance for the 13 different prior distributions. With a large number of studies the choice of prior distribution was less important. The effect size estimated was not biased, but the precision with which it was estimated varied with the choice of prior distribution leading to varying coverage intervals and, potentially, to different statistical inferences. Again there was less of a problem with a larger number of studies. There is a particular problem if the between-study variance is close to the boundary at zero, as MCMC results tend to produce upwardly biased estimates of the between-study variance, particularly if inferences are based on the posterior mean. The choice of 'vague' prior distribution can lead to a marked variation in results, particularly in small studies. Sensitivity to the choice of prior distribution should always be assessed.

Consumption of the putative chemopreventive agent curcumin by cancer patients: assessment of curcumin levels in the colorectum and their pharmacodynamic consequences.

Abstract: Curcumin, a constituent of the spice turmeric, has been shown to reduce the adenoma burden in rodent models of colorectal cancer accompanied by a reduction of levels of the oxidative DNA adduct 3-(2-deoxy-beta-di-erythro-pentafuranosyl)-pyr[1,2-alpha]-purin-10(3H)one (M(1)G) and of expression of the enzyme cyclooxygenase-2 (COX-2). We tested the hypothesis that pharmacologically active levels of curcumin can be achieved in the colorectum of humans as measured by effects on levels of M(1)G and COX-2 protein. Patients with colorectal cancer ingested curcumin capsules (3,600, 1,800, or 450 mg daily) for 7 days. Biopsy samples of normal and malignant colorectal tissue, respectively, were obtained at diagnosis and at 6 to 7 hours after the last dose of curcumin. Blood was taken 1 hour after the last dose of curcumin. Curcumin and its metabolites were detected and quantitated by high-performance liquid chromatography with detection by UV spectrophotometry or mass spectrometry. M(1)G levels and COX-2 protein expression were measured by immunoslot blot and Western blotting, respectively. The concentrations of curcumin in normal and malignant colorectal tissue of patients receiving 3,600 mg of curcumin were 12.7 +/- 5.7 and 7.7 +/- 1.8 nmol/g, respectively. Curcumin sulfate and curcumin glucuronide were identified in the tissue of these patients. Trace levels of curcumin were found in the peripheral circulation. M(1)G levels were 2.5-fold higher in malignant tissue as compared with normal tissue (P < 0.05 by ANOVA). Administration of curcumin (3,600 mg) decreased M(1)G levels from 4.8 +/- 2.9 adducts per 107 nucleotides in malignant colorectal tissue to 2.0 +/- 1.8 adducts per 107 nucleotides (P < 0.05 by ANOVA). COX-2 protein levels in malignant colorectal tissue were not affected by curcumin. The results suggest that a daily dose of 3.6 g curcumin achieves pharmacologically efficacious levels in the colorectum with negligible distribution of curcumin outside the gut.

Gas-phase radical chemistry in the troposphere

Abstract: Atmospheric free radicals are low concentration, relatively fast reacting species whose influence is felt throughout the atmosphere. Reactive radicals have a key role in maintaining a balanced atmospheric composition through their central function in controlling the oxidative capacity of the atmosphere. In this tutorial review, the chemistry of three main groups of atmospheric radicals HOx, NOx and XOx (X = Cl, Br, I) are examined in terms of their sources, interconversions and sinks. Key examples of the chemistry are given for each group of radicals in their atmospheric context.

Trunk Muscle Stabilization Training Plus General Exercise Versus General Exercise Only: Randomized Controlled Trial of Patients With Recurrent Low Back Pain

Abstract: BACKGROUND AND PURPOSE: The purpose of this randomized controlled trial was to examine the usefulness of the addition of specific stabilization exercises to a general back and abdominal muscle exercise approach for patients with subacute or chronic nonspecific back pain by comparing a specific muscle stabilization-enhanced general exercise approach with a general exercise-only approach. SUBJECTS: Fifty-five patients with recurrent, nonspecific back pain (stabilization-enhanced exercise group: n=29, general exercise-only group: n=26) and no clinical signs suggesting spinal instability were recruited. METHODS: Both groups received an 8-week exercise intervention and written advice (The Back Book). Outcome was based on self-reported pain (Short-Form McGill Pain Questionnaire), disability (Roland-Morris Disability Questionnaire), and cognitive status (Pain Self-Efficacy Questionnaire, Tampa Scale of Kinesiophobia, Pain Locus of Control Scale) measured immediately before and after intervention and 3 months after the end of the intervention period. RESULTS: Outcome measures for both groups improved. Furthermore, self-reported disability improved more in the general exercise-only group immediately after intervention but not at the 3-month follow-up. There were generally no differences between the 2 exercise approaches for any of the other outcomes. DISCUSSION AND CONCLUSION: A general exercise program reduced disability in the short term to a greater extent than a stabilization-enhanced exercise approach in patients with recurrent nonspecific low back pain. Stabilization exercises do not appear to provide additional benefit to patients with subacute or chronic low back pain who have no clinical signs suggesting the presence of spinal instability.

Non‐linear X‐ray variability in X‐ray binaries and active galaxies

Abstract: We show that the rms-flux relation recently discovered in the X-ray light curves of Active Galactic Nuclei (AGN) and X-ray binaries (XRBs) implies that the light curves have a formally non-linear, exponential form, provided the rms-flux relation applies to variations on all time-scales (as it appears to). This phenomenological model implies that stationary data will have a log normal flux distribution. We confirm this result using an observation of Cyg X-1, and further demonstrate that our model predicts the existence of the powerful millisecond flares observed in Cyg X-1 in the low/hardstate, and explains the general shape and amplitude of the bicoherence spectrum in that source. Our model predicts that the most variable light curves will show the most extreme non-linearity. This result can naturally explain the apparent non-linear variability observed in some highly variable Narrow Line Seyfert 1 (NLS1) galaxies, as well as the low states observed on long time-scales in the NLS1 NGC 4051, as being nothing more than extreme manifestations of the same variability process that is observed in XRBs and less variable AGN. That variability process must be multiplicative (with variations coupled together on all time-scales) and cannot be additive (such as shot-noise), or related to self-organised criticality, or result from completely independent variations in many separate emitting regions. Successful models for variability must reproduce the observed rms-flux relation and non-linear behaviour, which are more fundamental characteristics of the variability process than the power spectrum or spectral-timing properties. Models where X-ray variability is driven by accretion rate variations produced at different radii remain the most promising.