Fragmenting densely mineralised acellular protrusions from articular calcified cartilage: a role in osteoarthritis?

Fragmenting densely mineralised acellular protrusions from articular calcified cartilage: a role in osteoarthritis? A. Boyde a, G.R. Davis a, D. Mills a, T. Zikmund a, V.L. Adams b, L.R. Ranganath b, N. Jeffery b, J.A. Gallagher b a Dental Physical Sciences, Oral Growth and Development, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK b Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK Objectives High density mineralised protrusions (HDMP) from the tidemark mineralising front into hyaline articular cartilage (HAC) were first discovered in Thoroughbred racehorse fetlock joints and later in Icelandic horse hock joints. If these fragment, they could make a significant contribution to joint destruction in osteoarthritis. We looked for them in human material. Methods Whole femoral heads removed at operation for joint replacement or from dissection room cadavers were studied by MRI DESS at 0.23mm resolution and 26 micron resolution high contrast x-ray microtomography (XMT), then sectioned and embedded in PMMA, and block faces polished and the blocks re-imaged with 6 micron resolution XMT. Tissue mineralisation density was imaged qualitatively by backscattered electron SEM (BSE SEM) at 20kV using uncoated samples at 50Pa chamber pressure to achieve charge neutralisation. HAC histology was studied by BSE SEM after staining block faces with ammonium triiodide solution. Block surfaces were sequentially repolished and restained. Results Figure: 3D rendering of 6 micron voxel resolution XMT data set showing HDMP complex projecting above subchondral bone plate. Human femoral head removed at arthroplasty. We found examples of HDMP in HAC in human hips. Their 3D shapes are complex and may show cutting blade forms. Their mineral content (a) exceeds that of articular calcified cartilage (ACC), otherwise the densest tissue in the joint and (b) is not uniform. The mineral phase morphology frequently shows the agglomeration of many fine particles into larger concretions. Cracks within them are frequent. Dense fragments may be found within damaged HAC. Conclusions HDMP arise via the extrusion of an uncharacterised matrix into clefts in HAC. Little evidence of their existence remains after tissue has been decalcified with usual histological protocols. Their formation may be an extension of a normal but poorly recognised crack self-healing mechanism found in bone and ACC. They are surrounded by HAC, are dense and brittle and show innumerable fault lines within them. We provide evidence that they break in vivo by being able to find matching fragments in HAC. We conclude that these hard and sharp particles contribute to the shredding destruction of HAC. The osteoarthritis research community should be aware of their existence so that the frequency and possible clinical significance can be assessed in the future. Larger HDMP can be detected with the best MRI imaging

Growth and dislocation studies of β-HMX

Background: The defect structure of organic materials is important as it plays a major role in their crystal growth properties. It also can play a subcritical role in “hot-spot” detonation processes of energetics and one such energetic is cyclotetramethylene-tetranitramine, in the commonly used beta form (β-HMX). Results: The as-grown crystals grown by evaporation from acetone show prismatic, tabular and columnar habits, all with {011}, {110}, (010) and (101) faces. Etching on (010) surfaces revealed three different types of etch pits, two of which could be identified with either pure screw or pure edge dislocations, the third is shown to be an artifact of the twinning process that this material undergoes. Examination of the {011} and {110} surfaces show only one type of etch pit on each surface; however their natural asymmetry precludes the easy identification of their Burgers vector or dislocation type. Etching of cleaved {011} surfaces demonstrates that the etch pits can be associated with line dislocations. All dislocations appear randomly on the crystal surfaces and do not form alignments characteristic of mechanical deformation by dislocation slip. Conclusions: Crystals of β-HMX grown from acetone show good morphological agreement with that predicted by modelling, with three distinct crystal habits observed depending upon the supersaturation of the growth solution. Prismatic habit was favoured at low supersaturation, while tabular and columnar crystals were predominant at higher super saturations. The twin plane in β-HMX was identified as a (101) reflection plane. The low plasticity of β-HMX is shown by the lack of etch pit alignments corresponding to mechanically induced dislocation arrays. On untwinned {010} faces, two types of dislocations exist, pure edge dislocations with b = [010] and pure screw dislocations with b = [010]. On twinned (010) faces, a third dislocation type exists and it is proposed that these pits are associated with pure screw dislocations with b = [010]

External sources of clean technology: evidence from the clean development mechanism

New technology is fundamental to sustainable development. However, inventors from industrialized countries often refuse technology transfer because they worry about reverse-engineering. When can clean technology transfer succeed? We develop a formal model of the political economy of North–South technology transfer. According to the model, technology transfer is possible if (1) the technology in focus has limited global commercial potential or (2) the host developing country does not have the capacity to absorb new technologies for commercial use. If both conditions fail, inventors from industrialized countries worry about the adverse competitiveness effects of reverse-engineering, so technology transfer fails. Data analysis of technology transfer in 4,894 projects implemented under the Kyoto Protocol’s Clean Development Mechanism during the 2004–2010 period provides evidence in support of the model

An upper limit on the contribution of accreting white dwarfs to the type Ia supernova rate

There is wide agreement that Type Ia supernovae (used as standard candles for cosmology) are associated with the thermonuclear explosions of white dwarf stars. The nuclear runaway that leads to the explosion could start in a white dwarf gradually accumulating matter from a companion star until it reaches the Chandrasekhar limit, or could be triggered by the merger of two white dwarfs in a compact binary system. The X-ray signatures of these two possible paths are very different. Whereas no strong electromagnetic emission is expected in the merger scenario until shortly before the supernova, the white dwarf accreting material from the normal star becomes a source of copious X-rays for ~1e7 yr before the explosion. This offers a means of determining which path dominates. Here we report that the observed X-ray flux from six nearby elliptical galaxies and galaxy bulges is a factor of ~30-50 less than predicted in the accretion scenario, based upon an estimate of the supernova rate from their K-band luminosities. We conclude that no more than ~5 per cent of Type Ia supernovae in early type galaxies can be produced by white dwarfs in accreting binary systems, unless their progenitors are much younger than the bulk of the stellar population in these galaxies, or explosions of sub-Chandrasekhar white dwarfs make a significant contribution to the supernova rate.Comment: 10 pages, 1 tabl

Detection of Massive Forming Galaxies at Redshifts Greater than One

The complex problem of when and how galaxies formed has not until recently been susceptible of direct attack. It has been known for some time that the excessive number of blue galaxies counted at faint magnitudes implies that a considerable fraction of the massive star formation in the universe occurred at z < 3, but, surprisingly, spectroscopic studies of galaxies down to a B magnitude of 24 found little sign of the expected high-z progenitors of current massive galaxies, but rather, in large part, small blue galaxies at modest redshifts z \sim 0.3. This unexpected population has diverted attention from the possibility that early massive star-forming galaxies might also be found in the faint blue excess. From KECK spectroscopic observations deep enough to encompass a large population of z > 1 field galaxies, we can now show directly that in fact these forming galaxies are present in substantial numbers at B \sim 24, and that the era from redshifts 1 to 2 was clearly a major period of galaxy formation. These z > 1 galaxies have very unusual morphologies as seen in deep HST WFPC2 images.Comment: 10 pages LaTeX + 5 PostScript figures in uuencoded gzipped tar file; aasms4.sty, flushrt.sty, overcite.sty (the two aastex4.0 and overcite.sty macros are available from xxx.lanl.gov) Also available (along with style files) via anonymous ftp to ftp://hubble.ifa.hawaii.edu/pub/preprints . E-print version of paper adds citation cross-references to other archived e-prints, where available. To appear in Nature October 19, 199

Sunscreens - Which and what for?

It is well established that sun exposure is the main cause for the development of skin cancer. Chronic continuous UV radiation is believed to induce malignant melanoma, whereas intermittent high-dose UV exposure contributes to the occurrence of actinic keratosis as precursor lesions of squamous cell carcinoma as well as basal cell carcinoma. Not only photocarcinogenesis but also the mechanisms of photoaging have recently become apparent. In this respect the use of sunscreens seemed to prove to be more and more important and popular within the last decades. However, there is still inconsistency about the usefulness of sunscreens. Several studies show that inadequate use and incomplete UV spectrum efficacy may compromise protection more than previously expected. The sunscreen market is crowded by numerous products. Inorganic sunscreens such as zinc oxide and titanium oxide have a wide spectral range of activity compared to most of the organic sunscreen products. It is not uncommon for organic sunscreens to cause photocontact allergy, but their cosmetic acceptability is still superior to the one given by inorganic sunscreens. Recently, modern galenic approaches such as micronization and encapsulation allow the development of high-quality inorganic sunscreens. The potential systemic toxicity of organic sunscreens has lately primarily been discussed controversially in public, and several studies show contradictory results. Although a matter of debate, at present the sun protection factor (SPF) is the most reliable information for the consumer as a measure of sunscreen filter efficacy. In this context additional tests have been introduced for the evaluation of not only the protective effect against erythema but also protection against UV-induced immunological and mutational effects. Recently, combinations of UV filters with agents active in DNA repair have been introduced in order to improve photoprotection. This article reviews the efficacy of sunscreens in the prevention of epithelial and nonepithelial skin cancer, the effect on immunosuppression and the value of the SPF as well as new developments on the sunscreen market. Copyright (C) 2005 S. Karger AG, Basel

Modulation of emotional appraisal by false physiological feedback during fMRI

BACKGROUND James and Lange proposed that emotions are the perception of physiological reactions. Two-level theories of emotion extend this model to suggest that cognitive interpretations of physiological changes shape self-reported emotions. Correspondingly false physiological feedback of evoked or tonic bodily responses can alter emotional attributions. Moreover, anxiety states are proposed to arise from detection of mismatch between actual and anticipated states of physiological arousal. However, the neural underpinnings of these phenomena previously have not been examined. METHODOLOGY/PRINCIPAL FINDINGS We undertook a functional brain imaging (fMRI) experiment to investigate how both primary and second-order levels of physiological (viscerosensory) representation impact on the processing of external emotional cues. 12 participants were scanned while judging face stimuli during both exercise and non-exercise conditions in the context of true and false auditory feedback of tonic heart rate. We observed that the perceived emotional intensity/salience of neutral faces was enhanced by false feedback of increased heart rate. Regional changes in neural activity corresponding to this behavioural interaction were observed within included right anterior insula, bilateral mid insula, and amygdala. In addition, right anterior insula activity was enhanced during by asynchronous relative to synchronous cardiac feedback even with no change in perceived or actual heart rate suggesting this region serves as a comparator to detect physiological mismatches. Finally, BOLD activity within right anterior insula and amygdala predicted the corresponding changes in perceived intensity ratings at both a group and an individual level. CONCLUSIONS/SIGNIFICANCE Our findings identify the neural substrates supporting behavioural effects of false physiological feedback, and highlight mechanisms that underlie subjective anxiety states, including the importance of the right anterior insula in guiding second-order "cognitive" representations of bodily arousal state

OSTEOARTHRITIC SUBCHONDRAL BONE MARROW HISTOLOGY. LESSONS FROM CHANGES IN ALKAPTONURIA

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Does publication bias inflate the apparent efficacy of psychological treatment for major depressive disorder? A systematic review and meta-analysis of US national institutes of health-funded trials

Background The efficacy of antidepressant medication has been shown empirically to be overestimated due to publication bias, but this has only been inferred statistically with regard to psychological treatment for depression. We assessed directly the extent of study publication bias in trials examining the efficacy of psychological treatment for depression. Methods and Findings We identified US National Institutes of Health grants awarded to fund randomized clinical trials comparing psychological treatment to control conditions or other treatments in patients diagnosed with major depressive disorder for the period 1972–2008, and we determined whether those grants led to publications. For studies that were not published, data were requested from investigators and included in the meta-analyses. Thirteen (23.6%) of the 55 funded grants that began trials did not result in publications, and two others never started. Among comparisons to control conditions, adding unpublished studies (Hedges’ g = 0.20; CI95% -0.11~0.51; k = 6) to published studies (g = 0.52; 0.37~0.68; k = 20) reduced the psychotherapy effect size point estimate (g = 0.39; 0.08~0.70) by 25%. Moreover, these findings may overestimate the "true" effect of psychological treatment for depression as outcome reporting bias could not be examined quantitatively. Conclusion The efficacy of psychological interventions for depression has been overestimated in the published literature, just as it has been for pharmacotherapy. Both are efficacious but not to the extent that the published literature would suggest. Funding agencies and journals should archive both original protocols and raw data from treatment trials to allow the detection and correction of outcome reporting bias. Clinicians, guidelines developers, and decision makers should be aware that the published literature overestimates the effects of the predominant treatments for depression