Uterine tumours are a phenotypic manifestation of the hyperparathyroidism-jaw tumour syndrome

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74672/1/j.1365-2796.2004.01421.x.pd

Systems biological and mechanistic modelling of radiation-induced cancer

This paper summarises the five presentations at the First International Workshop on Systems Radiation Biology that were concerned with mechanistic models for carcinogenesis. The mathematical description of various hypotheses about the carcinogenic process, and its comparison with available data is an example of systems biology. It promises better understanding of effects at the whole body level based on properties of cells and signalling mechanisms between them. Of these five presentations, three dealt with multistage carcinogenesis within the framework of stochastic multistage clonal expansion models, another presented a deterministic multistage model incorporating chromosomal aberrations and neoplastic transformation, and the last presented a model of DNA double-strand break repair pathways for second breast cancers following radiation therapy

Considering the role of cognitive control in expert performance

© 2014, Springer Science+Business Media Dordrecht. Dreyfus and Dreyfus’ (1986) influential phenomenological analysis of skill acquisition proposes that expert performance is guided by non-cognitive responses which are fast, effortless and apparently intuitive in nature. Although this model has been criticised (e.g., by Breivik Journal of Philosophy of Sport, 34, 116–134 2007, Journal of the Philosophy of Sport, 40, 85–106 2013; Eriksen 2010; Montero Inquiry:An interdisciplinary Journal of Philosophy, 53, 105–122 2010; Montero and Evans 2011) for over-emphasising the role that intuition plays in facilitating skilled performance, it does recognise that on occasions (e.g., when performance goes awry for some reason) a form of ‘detached deliberative rationality’ may be used by experts to improve their performance. However, Dreyfus and Dreyfus (1986) see no role for calculative problem solving or deliberation (i.e., drawing on rules or mental representations) when performance is going well. In the current paper, we draw on empirical evidence, insights from athletes, and phenomenological description to argue that ‘continuous improvement’ (i.e., the phenomenon whereby certain skilled performers appear to be capable of increasing their proficiency even though they are already experts; Toner and Moran 2014) among experts is mediated by cognitive (or executive) control in three distinct sporting situations (i.e., in training, during pre-performance routines, and while engaged in on-line skill execution). We conclude by arguing that Sutton et al. Journal of the British Society for Phenomenology, 42, 78–103 (2011) ‘applying intelligence to the reflexes’ (AIR) approach may help to elucidate the process by which expert performers achieve continuous improvement through analytical/mindful behaviour during training and competition

Canadian and English students' beliefs about waterpipe smoking: a qualitative study

<p>Abstract</p> <p>Background</p> <p>Waterpipe smoking is becoming popular among western students. The aim was to understand the appeal to students of this form of smoking when other forms of smoking are becoming less common.</p> <p>Methods</p> <p>Waterpipe smokers were identified by snowball sampling and interviewed following a semi-structured schedule in waterpipe cafes and in their homes. Constant comparative analysis was used to derive themes for the analysis.</p> <p>Results</p> <p>Waterpipe smokers saw smoking as an alternative to more expensive nights out in bars. The appeal was related to the communal activity and the novelty of the experience. Respondents had not thought deeply about the health risks and reasoned that if no warnings about waterpipe smoking were apparent (unlike cigarette smoking) then it was probably safe. These observations were reinforced by observations about the mildness of the smoke, the fruit flavours, and beliefs about the filtering of the water. Waterpipe smokers felt no pressure to stop smoking and therefore had not tried to do so, but felt it might be something they did not continue after university. Waterpipe smoking was not linked in students' minds to other forms of smoking except in one individual who was using waterpipe smoking to help quit cigarettes.</p> <p>Conclusion</p> <p>In the absence of public health information, students have fallen back on superficial experiences to form views that waterpipe smoking is less harmful than other forms of smoking and it is currently much more acceptable in student society than other forms of smoking.</p

Big conductance calcium-activated potassium channel openers control spasticity without sedation.

BACKGROUND AND PURPOSE: Our initial aim was to generate cannabinoid agents that control spasticity, occurring as a consequence of multiple sclerosis (MS), whilst avoiding the sedative side effects associated with cannabis. VSN16R was synthesized as an anandamide (endocannabinoid) analogue in an anti-metabolite approach to identify drugs that target spasticity. EXPERIMENTAL APPROACH: Following the initial chemistry, a variety of biochemical, pharmacological and electrophysiological approaches, using isolated cells, tissue-based assays and in vivo animal models, were used to demonstrate the activity, efficacy, pharmacokinetics and mechanism of action of VSN16R. Toxicological and safety studies were performed in animals and humans. KEY RESULTS: VSN16R had nanomolar activity in tissue-based, functional assays and dose-dependently inhibited spasticity in a mouse experimental encephalomyelitis model of MS. This effect occurred with over 1000-fold therapeutic window, without affecting normal muscle tone. Efficacy was achieved at plasma levels that are feasible and safe in humans. VSN16R did not bind to known CB1 /CB2 /GPPR55 cannabinoid-related receptors in receptor-based assays but acted on a vascular cannabinoid target. This was identified as the major neuronal form of the big conductance, calcium-activated potassium (BKCa ) channel. Drug-induced opening of neuronal BKCa channels induced membrane hyperpolarization, limiting excessive neural-excitability and controlling spasticity. CONCLUSIONS AND IMPLICATIONS: We identified the neuronal form of the BKCa channel as the target for VSN16R and demonstrated that its activation alleviates neuronal excitability and spasticity in an experimental model of MS, revealing a novel mechanism to control spasticity. VSN16R is a potential, safe and selective ligand for controlling neural hyper-excitability in spasticity

Simulation of cell-substrate traction force dynamics in response to soluble factors

Finite element (FE) simulations of contractile responses of vascular muscular thin films (vMTFs) and endothelial cells resting on an array of micro-posts under stimulation of soluble factors were conducted in comparison with experimental measurements reported in literature. Two types of constitutive models were employed in the simulations, i.e. smooth muscle cell type and non-smooth muscle cell type. The time histories of the effects of soluble factors were obtained via calibration against experimental measurements of contractile responses of tissues or cells. The numerical results for vMTFs with micropatterned tissues suggest that the radius of curvature of vMTFs under stimulation of soluble factors is sensitive to width of the micropatterned tissue, i.e. the radius of curvature increases as the tissue width decreases. However, as the tissue response is essentially isometric, the time history of the maximum principal stress of the micropatterned tissues is not sensitive to tissue width. Good agreement has been achieved for predictions of the vasoconstrictor endothelin-1 (ET-1) induced contraction stress between the FE numerical simulation and the experiment based approach of Alford, et al. (2011) for the vMTFs with 40, 60, 80 and 100 μm width patterns. This may suggest the contraction stress is weakly sensitive to the tissue width for these patterns. However, for 20 μm width tissue patterning, the numerical simulation result for contraction stress is less than the average value of experimental measurements, which may suggest the thinner and more elongated spindle-like cells within the 20 μm width tissue patterning have higher contractile output. The constitutive model for non-smooth muscle cells was used to simulate the contractile response of the endothelial cells. The substrate was treated as an effective continuum. For agonists such as Lysophosphatidic acid (LPA) and vascular endothelial growth factor (VEGF), the deformation of the cell diminishes from edge to centre and the central part of the cell is essentially under isometric state. Numerical studies demonstrated the scenarios that cell polarity can be triggered via manipulation of the effective stiffness and Possion’s ratio of the substrate

Evidence for the return of subducted continental crust

Author Posting. © Nature Publishing Group, 2007. This is the author's version of the work. It is posted here by permission of Nature Publishing Group for personal use, not for redistribution. The definitive version was published in Nature 448 (2007): 684-687, doi:10.1038/nature06048.Substantial quantities of terrigenous sediments are known to enter the mantle at subduction zones, but little is known about their fate in the mantle. Subducted sediment may be entrained in buoyantly upwelling plumes and returned to the earth’s surface at hotspots, but the proportion of recycled sediment in the mantle is small and clear examples of recycled sediment in hotspot lavas are rare. We report here remarkably enriched 87Sr/86Sr and 143Nd/144Nd isotope signatures (up to 0.720830 and 0.512285, respectively) in Samoan lavas from three dredge locations on the underwater flanks of Savai’i island, Western Samoa. The submarine Savai’i lavas represent the most extreme 87Sr/86Sr isotope compositions reported for ocean island basalts (OIBs) to date. The data are consistent with the presence of a recycled sediment component (with a composition similar to upper continental crust, or UCC) in the Samoan mantle. Trace element data show similar affinities with UCC—including exceptionally low Ce/Pb and Nb/U ratios—that complement the enriched 87Sr/86Sr and 143Nd/144Nd isotope signatures. The geochemical evidence from the new Samoan lavas radically redefines the composition of the EM2 (enriched mantle 2) mantle endmember, and points to the presence of an ancient recycled UCC component in the Samoan plume

Zircon ages in granulite facies rocks: decoupling from geochemistry above 850 °C?

Granulite facies rocks frequently show a large spread in their zircon ages, the interpretation of which raises questions: Has the isotopic system been disturbed? By what process(es) and conditions did the alteration occur? Can the dates be regarded as real ages, reflecting several growth episodes? Furthermore, under some circumstances of (ultra-)high-temperature metamorphism, decoupling of zircon U–Pb dates from their trace element geochemistry has been reported. Understanding these processes is crucial to help interpret such dates in the context of the P–T history. Our study presents evidence for decoupling in zircon from the highest grade metapelites (> 850 °C) taken along a continuous high-temperature metamorphic field gradient in the Ivrea Zone (NW Italy). These rocks represent a well-characterised segment of Permian lower continental crust with a protracted high-temperature history. Cathodoluminescence images reveal that zircons in the mid-amphibolite facies preserve mainly detrital cores with narrow overgrowths. In the upper amphibolite and granulite facies, preserved detrital cores decrease and metamorphic zircon increases in quantity. Across all samples we document a sequence of four rim generations based on textures. U–Pb dates, Th/U ratios and Ti-in-zircon concentrations show an essentially continuous evolution with increasing metamorphic grade, except in the samples from the granulite facies, which display significant scatter in age and chemistry. We associate the observed decoupling of zircon systematics in high-grade non-metamict zircon with disturbance processes related to differences in behaviour of non-formula elements (i.e. Pb, Th, U, Ti) at high-temperature conditions, notably differences in compatibility within the crystal structure

The role of virulence factors in the outcome of staphylococcal peritonitis in CAPD patients

<p>Abstract</p> <p>Background</p> <p>Peritonitis continues to be the most frequent cause of peritoneal dialysis (PD) failure, with an important impact on patient mortality. Gram-positive cocci such as <it>Staphylococcus epidermidis</it>, other coagulase-negative staphylococci (CoNS), and <it>Staphylococcus aureus </it>are the most frequent etiological agents of PD-associated peritonitis worldwide. The objective of the present study was to compare peritonitis caused by <it>S. aureus </it>and CoNS and to evaluate the factors influencing outcome.</p> <p>Methods</p> <p>Records of 86 new episodes of staphylococcal peritonitis that occurred between 1996 and 2000 in the Dialysis unit of a single university hospital were studied (35 due to <it>S. aureus</it>, 24 to <it>S. epidermidis </it>and 27 to other CoNS). The production of slime, lipase, lecithinase, nuclease (DNAse), thermonuclease (TNAse), α- and β-hemolysin, enterotoxins (SEA, SEB, SEC, SED) and toxic shock syndrome toxin-1 (TSST-1) was studied in <it>S. aureus </it>and CoNS. Antimicrobial susceptibility was evaluated based on the minimal inhibitory concentration determined by the E-test. Outcome predictors were evaluated by two logistic regression models.</p> <p>Results</p> <p>The oxacillin susceptibility rate was 85.7% for <it>S. aureus</it>, 41.6% for <it>S. epidermidis</it>, and 51.8% for other CoNS (p = 0.001). Production of toxins and enzymes, except for enterotoxin A and α-hemolysin, was associated with <it>S. aureus </it>episodes (p < 0.001), whereas slime production was positive in 23.5% of CoNS and 8.6% of <it>S. aureus </it>strains (p = 0.0047). The first model did not include enzymes and toxins due to their association with <it>S. aureus</it>. The odds of resolution were 9.5 times higher for <it>S. epidermidis </it>than for <it>S. aureus </it>(p = 0.02) episodes, and were similar for <it>S. epidermidis </it>and other CoNS (p = 0.8). The resolution odds were 68 times higher for non-slime producers (p = 0.001) and were not influenced by oxacillin resistance among vancomycin-treated cases (p = 0.89). In the second model, the resolution rate was similar for <it>S. aureus </it>and <it>S. epidermidis </it>(p = 0.70), and slime (p = 0.001) and α-hemolysin (p = 0.04) production were independent predictors of non-resolution.</p> <p>Conclusion</p> <p>Bacterial species and virulence factors rather than antibiotic resistance influence the outcome of staphylococcal peritonitis.</p