Chinese Whispers: A brief history of eponymous orthopaedic examinations

Eponymous orthopaedic examinations frequently appear in modern clinical examinations, yet their original description and cause for change are often omitted from medical education today. This is important to appreciate in order to understand their diagnostic relevance in modern medicine and subsequent interpretation of results by fellow clinicians. This article reviews the original description of these tests by their namesakes, how they have evolved over time and their relevance in orthopaedics today. An online literature review (PubMed) was conducted of the original descriptions and other published literature detailing their history, evolution, sensitivity and specificity. While elements of these tests have been lost naturally over time to the ‘Chinese Whispers’ effect, most have evolved positively secondary to a deepening anatomical and pathological understanding of their target conditions. They retain some usefulness in clinical medicine, however it is recognized that their diagnostic value is invariably supplanted by improvements in diagnostic imaging

Chinese Whispers: A brief history of eponymous orthopaedic examinations

Eponymous orthopaedic examinations frequently appear in modern clinical examinations, yet their original description and cause for change are often omitted from medical education today. This is important to appreciate in order to understand their diagnostic relevance in modern medicine and subsequent interpretation of results by fellow clinicians. This article reviews the original description of these tests by their namesakes, how they have evolved over time and their relevance in orthopaedics today. An online literature review (PubMed) was conducted of the original descriptions and other published literature detailing their history, evolution, sensitivity and specificity. While elements of these tests have been lost naturally over time to the ‘Chinese Whispers’ effect, most have evolved positively secondary to a deepening anatomical and pathological understanding of their target conditions. They retain some usefulness in clinical medicine, however it is recognized that their diagnostic value is invariably supplanted by improvements in diagnostic imaging

Striatal neuropeptides enhance selection and rejection of sequential actions

The striatum is the primary input nucleus for the basal ganglia, and receives glutamatergic afferents from the cortex. Under the hypothesis that basal ganglia perform action selection, these cortical afferents encode potential “action requests.” Previous studies have suggested the striatum may utilize a mutually inhibitory network of medium spiny neurons (MSNs) to filter these requests so that only those of high salience are selected. However, the mechanisms enabling the striatum to perform clean, rapid switching between distinct actions that form part of a learned action sequence are still poorly understood. Substance P (SP) and enkephalin are neuropeptides co-released with GABA in MSNs preferentially expressing D1 or D2 dopamine receptors respectively. SP has a facilitatory effect on subsequent glutamatergic inputs to target MSNs, while enkephalin has an inhibitory effect. Blocking the action of SP in the striatum is also known to affect behavioral transitions. We constructed phenomenological models of the effects of SP and enkephalin, and integrated these into a hybrid model of basal ganglia comprising a spiking striatal microcircuit and rate–coded populations representing other major structures. We demonstrated that diffuse neuropeptide connectivity enhanced the selection of unordered action requests, and that for true action sequences, where action semantics define a fixed structure, a patterning of the SP connectivity reflecting this ordering enhanced selection of actions presented in the correct sequential order and suppressed incorrect ordering. We also showed that selective pruning of SP connections allowed context–sensitive inhibition of specific undesirable requests that otherwise interfered with selection of an action group. Our model suggests that the interaction of SP and enkephalin enhances the contrast between selection and rejection of action requests, and that patterned SP connectivity in the striatum allows the “chunking” of actions and improves selection of sequences. Efficient execution of action sequences may therefore result from a combination of ordered cortical inputs and patterned neuropeptide connectivity within striatum

Antihydrogen formation dynamics in a multipolar neutral anti-atom trap

Antihydrogen production in a neutral atom trap formed by an octupole-based magnetic field minimum is demonstrated using field-ionization of weakly bound anti-atoms. Using our unique annihilation imaging detector, we correlate antihydrogen detection by imaging and by field-ionization for the first time. We further establish how field-ionization causes radial redistribution of the antiprotons during antihydrogen formation and use this effect for the first simultaneous measurements of strongly and weakly bound antihydrogen atoms. Distinguishing between these provides critical information needed in the process of optimizing for trappable antihydrogen. These observations are of crucial importance to the ultimate goal of performing CPT tests involving antihydrogen, which likely depends upon trapping the anti-atom

Oestrogen receptor β (ERβ) regulates osteogenic differentiation of human dental pulp cells

Estradiol (E2) has many important actions in the tissues of the oral cavity. Disruption of E2 metabolism or alterations in systemic E2 concentrations have been associated with compromised periodontal health. In many instances such changes occur secondarily to the well characterised effects of E2 on bone physiology –especially maintenance of bone mineral density (BMD). Despite these important epidemiological findings, little is known about the mechanism of action of E2 in oral tissues or the expression and function of oestrogen receptor (ER) isoforms in these tissues. We have isolated human dental pulp cells (hDPCs), which are able to differentiate towards an osteogenic lineage under appropriate culture conditions. We show that hDPCs express ERα, ERβ1, ERβ2 and the cell membrane associated G protein-coupled ER (GPR30). Following osteogenic differentiation of hDPCs, ERβ1 and ERβ2 were up regulated approximately 50-fold while ERα and GPR30 were down regulated, but to a much lesser degree (approximately 2-fold). ERβ was characterised as a 59 kDa protein following Western blot analysis with validated antibodies and ERβ was detected in both nuclear and cytoplasmic cell compartments following immunofluorescence (IF) and immunohistochemical (IHC) analysis of cultured cells. Furthermore isoform specific antibodies detected both ERβ1 and ERβ2 in DPC cultures and in situ analysis of ERβ expression in decalcified tooth/pulp sections identified the odontoblast layer of pulp cells juxtaposed to the tooth enamel as strongly reactive for both ERβ isoforms. Finally the use of isoform specific agonists identified ERβ as the main receptor responsible for the pro-osteogenic effect of oestrogenic hormones in this tissue. Our data suggest that oestrogens stimulated osteogenic differentiation in hDPCs and that this action is mediated principally through the ERβ isoform. These findings may have important consequences for the investigation and treatment of oral and periodontal pathologies which are associated with imbalances in oestrogen concentrations and action

A novel antiproton radial diagnostic based on octupole induced ballistic loss

We report results from a novel diagnostic that probes the outer radial profile of trapped antiproton clouds. The diagnostic allows us to determine the profile by monitoring the time-history of antiproton losses that occur as an octupole field in the antiproton confinement region is increased. We show several examples of how this diagnostic helps us to understand the radial dynamics of antiprotons in normal and nested Penning-Malmberg traps. Better understanding of these dynamics may aid current attempts to trap antihydrogen atoms

Search For Trapped Antihydrogen

We present the results of an experiment to search for trapped antihydrogen atoms with the ALPHA antihydrogen trap at the CERN Antiproton Decelerator. Sensitive diagnostics of the temperatures, sizes, and densities of the trapped antiproton and positron plasmas have been developed, which in turn permitted development of techniques to precisely and reproducibly control the initial experimental parameters. The use of a position-sensitive annihilation vertex detector, together with the capability of controllably quenching the superconducting magnetic minimum trap, enabled us to carry out a high-sensitivity and low-background search for trapped synthesised antihydrogen atoms. We aim to identify the annihilations of antihydrogen atoms held for at least 130 ms in the trap before being released over ~30 ms. After a three-week experimental run in 2009 involving mixing of 10^7 antiprotons with 1.3 10^9 positrons to produce 6 10^5 antihydrogen atoms, we have identified six antiproton annihilation events that are consistent with the release of trapped antihydrogen. The cosmic ray background, estimated to contribute 0.14 counts, is incompatible with this observation at a significance of 5.6 sigma. Extensive simulations predict that an alternative source of annihilations, the escape of mirror-trapped antiprotons, is highly unlikely, though this possibility has not yet been ruled out experimentally.Comment: 12 pages, 7 figure

Equal fitness paradigm explained by a trade-off between generation time and energy production rate

Most plant, animal and microbial species of widely varying body size and lifestyle are nearly equally fit as evidenced by their coexistence and persistence through millions of years. All organisms compete for a limited supply of organic chemical energy, derived mostly from photosynthesis, to invest in the two components of fitness: survival and production. All organisms are mortal because molecular and cellular damage accumulates over the lifetime; life persists only because parents produce offspring. We call this the equal fitness paradigm. The equal fitness paradigm occurs because: (1) there is a trade-off between generation time and productive power, which have equal-but-opposite scalings with body size and temperature; smaller and warmer organisms have shorter lifespans but produce biomass at higher rates than larger and colder organisms; (2) the energy content of biomass is essentially constant, ~22.4 kJ g−1 dry body weight; and (3) the fraction of biomass production incorporated into surviving offspring is also roughly constant, ~10–50%. As organisms transmit approximately the same quantity of energy per gram to offspring in the next generation, no species has an inherent lasting advantage in the struggle for existence. The equal fitness paradigm emphasizes the central importance of energy, biological scaling relations and power–time trade-offs in life history, ecology and evolution

Connective tissue growth factor is a new ligand of epidermal growth factor receptor

Chronic kidney disease is reaching epidemic proportions worldwide and there is no effective treatment. Connective tissue growth factor (CCN2) has been suggested as a risk biomarker and a potential therapeutic target for renal diseases, but its specific receptor has not been identified. Epidermal growth factor receptor (EGFR) participates in kidney damage, but whether CCN2 activates the EGFR pathway is unknown. Here, we show that CCN2 is a novel EGFR ligand. CCN2 binding to EGFR extracellular domain was demonstrated by surface plasmon resonance. CCN2 contains four distinct structural modules. The carboxyl-terminal module (CCN2(IV)) showed a clear interaction with soluble EGFR, suggesting that EGFR-binding site is located in this module. Injection of CCN2(IV) in mice increased EGFR phosphorylation in the kidney, mainly in tubular epithelial cells. EGFR kinase inhibition decreased CCN2(IV)-induced renal changes (ERK activation and inflammation). Studies in cultured tubular epithelial cells showed that CCN2(IV) binds to EGFR leading to ERK activation and proinflammatory factors overexpression. CCN2 interacts with the neurotrophin receptor TrkA, and EGFR/TrkA receptor crosstalk was found in response to CCN2(IV) stimulation. Moreover, endogenous CCN2 blockade inhibited TGF-β-induced EGFR activation. These findings indicate that CCN2 is a novel EGFR ligand that contributes to renal damage through EGFR signalling. © 2013 The Author