Adaptive responses to temperature in homogeneously and heterogeneously acclimated crabs

Walking leg closer muscle neuromuscular parameters were recorded electrophysiologically from homothermally and heterothermally acclimated Carcinus maenas (eurythermic) and Cancer pagurus (stenothermic). Homothermal (and immobilised) crabs of both species were acclimated to either 8 C or 22 C, whereas heterothermally acclimated crabs were acclimated to 8 C and 22 C coincidentally, exposing the animal's central nervous system (CNS) to either the warm (22 C) or cold (8 C) acclimation temperature. Thus, heterothermal acclimation exposes the CNS/endocrine system and one set of walking legs at one acclimation temperature, the contralateral walking legs are acclimated to the other acclimation temperature. This allowed an investigation into the CNS influence on the attainment of acclimation by walking legs. Comparisons of acclimation responses of the neuromuscular function of isolated walking legs from the same animal were done with respect to the walking leg and CNS acclimation temperatures experienced. Animals were acclimated for two weeks, recordings were taken of excitatory junctional potentials (EJP) etc., from dactylopodite closer muscle fibres when stimulated by the tonic motor axon over an experimental temperature range (6-26 C).The acclimation responses in homothermally exposed crabs of both species resulted in partial (Precht, type III) responses in resting potential, single and double pulse stimulated excitatory junctional potential amplitudes, these were interpreted as responses that allowed the maintenance of muscle function in the new thermal condition. With respect to long term thermal acclimation other electrophysiological parameters gave equivocal compensatory responses. Capacity acclimation responses were more complete in C.pagurus than C.maenas. In heterothermally acclimated animals resting potentials and EJP amplitudes revealed partial acclimation responses in a compensatory manner. Acclimation of heterothermally acclimated C.maenas and C.pagurus was determined to be independent of a CNS influence, indicating thermal acclimation was in response to the local tissue acclimation temperature

The effect of intramedullary pin size and monocortical screw configuration on locking compression plate-rod constructs in a in vitro fracture gap model

Objective: To investigate the effect of intramedullary (IM) pin size in combination with various monocortical screw configurations on construct stiffness and strength as well as plate stain in locking compression plate-rod (LCPR) constructs. Methods: A synthetic bone model with a 40mm fracture gap was used. LCPs with monocortical locking screws were tested with no pin (LCPMono) and IM pins of 20% (LCPR20), 30% (LCPR30) and 40% (LCPR40) of IM diameter. LCPs with bicortical screws (LCPBi) were also tested in the first paper. The first paper used screw configurations with 2 or 3 screws per fragment modelling long (8 hole), intermediate (6 hole) and short (4 hole) plate working lengths. Responses to axial compression, biplanar four point bending and axial load to failure were recorded. The second paper used 2 screws per fragment to model a long (8 hole) and short (4 hole) plate working length and strain responses to axial compression were recorded at 6 regions of the plate via 3D digital image correlation. Results: In the first paper, LCPBi were not significantly different from LCPMono control for any of the outcome variables measured. In bending, LCPR20 were not significantly different from LCPBi and LCPMono. LCPR30 were stiffer than LCPR20 and the controls. LCPR40 constructs were stiffer than all other constructs. The addition of an IM pin of any size provided a significant increase in axial stiffness and load to failure. This effect was incremental with increasing IM pin diameter. As plate working length decreased there was a significant increase in stiffness across all constructs. The addition of an IM pin of any size provided a significant decrease in plate strain. For the long working length, LCPR30 and LCPR40 had significantly lower strain than the LCPR20 and plate strain was significantly higher adjacent to the screw closest to the fracture site. For the short working length, there was no significant difference in strain across any LCPR constructs or at any region of the plate. Plate strain was significantly lower for the short working length compared to the long working length for LCPMono and LCPR20 but not LCPR30 and LCPR40. Conclusions: A pin of any size increases resistance to axial loads whereas a pin of at least 30% IM diameter is required to increase bending stiffness. Short plate working lengths provide maximum stiffness. However, the overwhelming effect of IM pin size obviates the effect of changing plate working length on construct stiffness. The increase in plate strain encountered with a long working length can be overcome by the use of a pin of 30-40% IM diameter. Where placement of a large diameter IM pin is not possible, screws should be placed as close to the fracture gap as possible to minimize plate strain and distribute it more evenly over the plate. Both studies showed a consistent effect of increasing IM pin diameter and using a short plate working length. However, a significant interaction effect between these variables was only detected on plate strain with the IM pin largely negating the effect of plate working length on construct stiffness

Stonehenge remodelled

We are pleased to present the latest account of the sequence of burial and construction at the site of Stonehenge, deduced by its most recent excavators and anchored in time by the application of Bayesian radiocarbon modelling. Five prehistoric stages are proposed, of varied duration, and related by our authors to neighbouring monuments in the Stonehenge environs. While it may never be possible to produce a definitive chronology for this most complex of monuments, the comprehensive and integrated achievement owed to these researchers has brought us much closer to that goal. It is from this firm platform that Stonehenge can begin its new era of communication with the public at large

Non-Steroidal Anti-Inflammatory Drugs in the Therapy of Canine Osteoarthritis

This thesis is in two parts. In the first three chapters the pathogenesis of osteoarthritis is discussed with particular reference to the mediators and enzymes involved. Current knowledge of medical treatment with analgesics, non-steroidal anti-inflammatory drugs (NSAIDs) and disease modifying drugs is presented. Chapters 4 and 5 detail experimental work on the NSAID carprofen and the steroid-NSAID combination PLT Tablets. Canine osteoarthritis usually occurs secondary to primary joint incongruity or instabilty but it may occur as a primary entity in older animals. Over the last two decades some of the ultrastructural pathogenic mechanisms of osteoarthritis have become clearer. Whatever the initiating cause of articular cartilage degeneration, there appear to be common mediator and enzyme pathways which induce biochemical and gross changes in articular cartilage and synovium. The chondrocyte reacts to alterations in pressure and forces within articular cartilage. The synovium liberates a number of mediators which affect chondrocyte metabolism. Free proteoglycan fragments in the synovial fluid induce synovial production of the cytokine interleukin-1. An increasingly important role is being ascribed to interleukins, and a number of other cytokines, growth factors and chondrocyte stress proteins may also be involved. There is evidence of humoral immune response to 'hidden' autoantigen in articular cartilage which is liberated as the cartilage is damaged. The degradation of the matrix appears to be due to enzymatic destruction of proteoglycan by neutral metalloproteinases which are produced in increased quantities by chondrocytes in osteoarthritic cartilage. A reduction in specific tissue inhibitors of metalloproteinases (TIMP) may make available increased amounts of free active metalloproteinases. Proteoglycan loss exposes the collagen network to enzymatic damage and also reduces the elasticity and residence of articular cartilage such that mechanical damage of collagen is possible. Loss of matrix may reduce the barrier to mediators in the synovial fluid. The net result is cartilage fibrillation and erosion. The treatment of osteoarthritis involves the avoidance or elimination of factors which promote joint damage such as joint instability, obesity, or inappropriate exercise. Analgesics are used to control the symptoms of pain and stiffness. The opiates are not recommended for long term use because of their central depressent effects. NSAIDs, which have analgesic and anti-inflammatory activity, have demonstrated better efficacy in osteoarthritis than pure analgesics such as paracetamol. The activity of NSAIDs is primarily due to the inhibition of the synthesis of prostanoids, some of which are beleived to mediate or modulate synovial inflammation and pain. The inhibition of prostaglandin synthesis by NSAIDs can be potentially damaging since it is responsible for toxic effects, particularly in gastrointestinal and renal tissue. The NSAIDs have different pharmacokinetics in different species and dose rates cannot be extrapolated between species. A number of drugs have been used in the dog. Some of the drugs used in man are much more toxic in dogs and should not be used. The drugs presently available are discussed in Chapter 3. A clinical trial on the efficacy of carprofen in the therapy of osteoarthritis in dogs was carried out with the cooperation of practicing veterinarians. Although a blinded cross-over trial with radiological corroboration of the clinical diagnosis would have been the prefered experimental method, it was not considered practical since no funds were available for the remuneration of participating veterinarians. Instead, it was only possible to perform an unblinded trial using two groups of limited comparability, and using phenylbutazone treated dogs as positive controls. The experimental evidence suggested that carprofen was at least as efficacious as phenylbutazone in the therapy of osteoarthritis and may be a useful drug in the chronic therapy of osteoarthritis at 2-4 mg/kg/day as a single dose or divided into two doses. PLT Tablets are a development of Predno-Leucotropin Tablets which have been used in the therapy of musculoskeletal disorders for 22 years. PLT Tablets contain the NSAID cinchophen and a low dose of the steroid prednisolone but, unlike Predno-Leucotropin Tablets, they do not contain hexamine. The combination may have synergistic activity since the two drugs have anti-inflammatory activity at different levels of the arachidonic acid conversion pathway. The prednisolone dose rate is similar to that demonstrated to have chondroprotective properties in early experimental osteoarthritis. A clinical trial on the efficacy of PLT Tablets was carried out since there are no reports in the veterinary literature on the efficacy of cinchophen, or of cinchophen and prednisolone in combination. Trial design resembled that for the carprofen clinical efficacy trial and had the same drawbacks. PLT Tablets appeared to be at least as efficacious as phenylbutazone in the therapy of osteoarthritis in the dog and were efficacious at dose rates below the manufacturers recommendations

International Negotiations on Farm Support Levels: The Role of PSEs

Agricultural and Food Policy, International Relations/Trade,

The bandmerged Planck Early Release Compact Source Catalogue: Probing sub-structure in the molecular gas at high Galactic latitude

The Planck Early Release Compact Source Catalogue (ERCSC) includes nine lists of highly reliable sources, individually extracted at each of the nine Planck frequency channels. To facilitate the study of the Planck sources, especially their spectral behaviour across the radio/infrared frequencies, we provide a "bandmerged" catalogue of the ERCSC sources. This catalogue consists of 15191 entries, with 79 sources detected in all nine frequency channels of Planck and 6818 sources detected in only one channel. We describe the bandmerging algorithm, including the various steps used to disentangle sources in confused regions. The multi-frequency matching allows us to develop spectral energy distributions of sources between 30 and 857 GHz, in particular across the 100 GHz band, where the energetically important CO J=1->0 line enters the Planck bandpass. We find ~3-5sigma evidence for contribution to the 100 GHz intensity from foreground CO along the line of sight to 147 sources with |b|>30 deg. The median excess contribution is 4.5+/-0.9 percent of their measured 100 GHz flux density which cannot be explained by calibration or beam uncertainties. This translates to 0.5+/-0.1 K km s^{-1} of CO which must be clumped on the scale of the Planck 100 GHz beam, i.e., ~10 arcmin. If this is due to a population of low mass (~15 Msun) molecular gas clumps, the total mass in these clumps may be more than 2000 Msun. Further, high-spatial-resolution, ground-based observations of the high-latitude sky will help shed light on the origin of this diffuse, clumpy CO emission.Comment: 15 pages, 15 figures, MNRAS in pres

The crux of the matter: did the ABC's Catalyst program change statin use in Australia?

This article argues that the ABC’s Catalyst program criticising statins affected people’s willingness to take these drugs. Abstract Objectives: To examine the impact of a two-part special edition of the Australian Broadcasting Corporation\u27s science journalism program Catalyst (titled Heart of the matter), aired in October 2013, that was critical of HMG-CoA reductase inhibitors (“statins”). Design, setting and participants: Population-based interrupted time-series analysis of a 10% sample of Australian long-term concessional beneficiaries who were dispensed statins under the Pharmaceutical Benefits Scheme (about 51% of all people who were dispensed a statin between 1 July 2009 and 30 June 2014); dispensing of proton pump inhibitors (PPIs) was used as a comparator. Main outcome measures: Change in weekly dispensings and discontinuation of use of statins and PPIs, adjusting for seasonal and long-term trends, overall and (for statins only) stratified by the use of cardiovascular and diabetes medicines. Results: In our sample, 191 833 people were dispensed an average of 26 946 statins weekly. Following the Catalyst program, there was a 2.60% (95% CI, 1.40%–3.77%; P < 0.001) reduction in statin dispensing, equivalent to 14 005 fewer dispensings Australia-wide every week. Dispensing decreased by 6.03% (95% CI, 3.73%–8.28%; P < 0.001) for people not dispensed other cardiovascular and diabetes medicines and 1.94% (0.42%–3.45%; P = 0.01) for those dispensed diabetes medicines. In the week the Catalyst program aired, there was a 28.8% (95% CI, 15.4%–43.7%; P < 0.001) increase in discontinuation of statin use, which decayed by 9% per week. An estimated 28 784 additional Australians ceased statin treatment. Discontinuation occurred regardless of the use of other cardiovascular and diabetes medicines. There were no significant changes in PPI use after the Catalyst program. Conclusions: Following airing of the Catalyst program, there was a temporary increase in discontinuation and a sustained decrease in overall statin dispensing. Up until 30 June 2014, there were 504 180 fewer dispensings of statins, and we estimate this to have affected 60 897 people

Membrane glucocorticoid receptors are localised in the extracellular matrix and signal through the MAPK pathway in mammalian skeletal muscle fibres

A number of studies have previously proposed the existence of glucocorticoid receptors on the plasma membrane of many cell types including skeletal muscle fibres. However, their exact localisation and the cellular signalling pathway(s) they utilise to communicate with the rest of the cell are still poorly understood. In this study, we investigated the localisation and the mechanism(s) underlying the non-genomic physiological functions of these receptors in mouse skeletal muscle cells. The results show that the receptors were localised in the cytoplasm in myoblasts, in the nucleus in myotubes and in the extracellular matrix, in satellite cells and in the proximity of mitochondria in adult muscle fibres. Also, they bound laminin in a glucocorticoid-dependent manner. Treating small skeletal muscle fibre bundles with the synthetic glucocorticoid, beclomethasone dipropionate, increased the phosphorylation (=activation) of extracellular-signal regulated kinase 1&2, c-Jun N-terminal kinase and p38 mitogen-activated protein kinase. This occurred within 5min and depended on the fibre-type and the duration of the treatment. It was also abolished by the glucocorticoid receptor inhibitor, mifepristone, and a monoclonal antibody against the receptor. From these results we conclude that the non-genomic/non-canonical physiological functions of glucocorticoids, in adult skeletal muscle fibres are mediated by a glucocorticoid receptor localised in the extracellular matrix, in satellite cells and close to mitochondria and involve activation of the MAPK pathway

Polarization Observations with the Cosmic Background Imager

We describe polarization observations of the CMBR with the Cosmic Background Imager, a 13 element interferometer which operates in the 26-36 GHz band from Llano de Chajnantour in northern Chile. The array consists of 90-cm Cassegrain antennas mounted on a steerable platform which can be rotated about the optical axis to facilitate polarization observations. The CBI employs single mode circularly polarized receivers which sample multipoles from ℓ~400 to ℓ~4250. The instrumental polarization of the CBI was calibrated with 3C279, a bright polarized point source which was monitored with the VLA