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An evidence base is vital to ensure well-informed policies with systematic processes.1,2 However, A research-to-policy gap exists that is widened by the discrepancy between the extensive time it takes to conduct conventional academic research and the short timescale over which policy-makers are often required to make decisions.2 This is especially concerning in times of crisis, such as the COVID-19 pandemic, that demanded an avalanche of data, analysis, and interpretation to be provided over a very short period of time. Rapid evaluation can be used to generate research-based evidence under pressure to inform decision-making and policy. Existing literature clearly details the steps involved in conducting rapid evaluation3; yet this literature contains little practical knowledge about how best to carry out such research. In this article, we reflect upon the practical implementation of rapid evaluation for an urgent project during the crisis of COVID-19.

The endemic Tasmanian Digger Wasp Williamsita tasmanica is only known from 13 registered museum specimens, with little recorded on its life history. A nesting aggregation of females was observed over a 25-day period, enabling the first detailed observations of host log, nest design, prey and egg deposition, and behavioural patterns to be made. Cells were provisioned with large flies (order Diptera) of nine species from nine genera and four families to observe behaviour. This aggregation used a large eucalypt with an exposed core of friable brown rot for nesting. Our study showed that the day-to-day behaviour of the female is predictable, centring on nest construction, hunting large flies and egg-laying. This information has been lodged on the Atlas of Living Australia and voucher specimens collected for the Queen Victoria Museum and Art Gallery to facilitate further taxonomic study.

The production, conversion, and storage of large quantities of energy require the use of high-temperature electrochemical devices: solid oxide fuel cells and electrolyzers. These depend upon the activity of the surface, and the mobility of ions in the main materials used in these devices. Here the up-to-date ion beam techniques used to interrogate these materials are presented: mainly secondary ion mass spectrometry and low energy ion spectroscopy. Some examples of the use of these techniques and recent successes in inaccurately determining ion mobilities in a number of complex structures are presented. The challenges faced by the techniques to address the materials that operate at high temperature are also discussed.

The behaviour of titanium substrates was investigated as replacements for transparent fluorine-doped tin oxide-coated glass substrates, the low conductivity of which causes inhomogeneous spatial distributions of potential and current densities on scaling up photo-electrodes in photo-electrochemical reactors. Hence, Fe2O3 (ca. 23 nm thick) was deposited by spray pyrolysis onto the titanium surface at 450 °C in air, causing growth of (less photo-active) rutile by thermal oxidation, the thickness being measured as ca. 20 nm by secondary ion mass spectrometry. Anodising titanium in aqueous phosphoric acid enabled ca. 12 nm anatase TiO2 to be grown prior to spray pyrolysis, limiting the subsequent thermal growth of rutile, so the overall TiO2 thickness was ca. 16 nm. 23 nm thick Fe2O3 deposited on a 22 nm TiO2 | Ti substrate after heat treatment at 500 °C for 1 hour was found to produced greater current densities than Fe2O3 deposited onto TEC-8 fluorine-doped tin oxide coated on glass; uv absorption by TiO2 and reflection by the titanium substrate contributed to measured photo-current densities.

The behavior of the layered Fe3+ perovskite superstructure with composition Ba1.7Ca2.4Y0.9Fe5O13 (BCYF) as an intermediate temperature solid oxide fuel cell (IT-SOFC) cathode is investigated by an ...

Employing small angle X-ray scattering (SAXS) and wide angle X-ray scattering (WAXS) combined with laser-heated aerodynamic levitation has enabled different transitions in supercooled yttrium oxide–aluminium oxide to be distinguished. These include liquid–liquid phase transitions as well as high temperature crystallization for different compositions. Prerequisites for avoiding crystallization in order to reveal polyamorphic phase separation in the supercooled state are established. We also show how the rise in SAXS intensity at low wavevectors can be used to identify correlation distances in long range fluctuations in high temperature melts. These distances appear to scale with melt viscosity and to extend temporarily during liquid–liquid transitions.

Stromatolites composed of apatite occur in post-Lomagundi-Jatuli successions (late Palaeoproterozoic) and suggest the emergence of novel types of biomineralization at that time. The microscopic and nanoscopic petrology of organic matter in stromatolitic phosphorites might provide insights into the suite of diagenetic processes that formed these types of stromatolites. Correlated geochemical micro-analyses of the organic matter could also yield molecular, elemental and isotopic compositions and thus insights into the role of specific micro-organisms among these communities. Here, we report on the occurrence of nanoscopic disseminated organic matter in the Palaeoproterozoic stromatolitic phosphorite from the Aravalli Supergroup of north-west India. Organic petrography by micro-Raman and Transmission Electron Microscopy demonstrates syngeneity of the organic matter. Total organic carbon contents of these stromatolitic phosphorite columns are between 0.05 and 3.0 wt% and have a large range of δ(13) Corg values with an average of -18.5‰ (1σ = 4.5‰). δ(15) N values of decarbonated rock powders are between -1.2 and +2.7‰. These isotopic compositions point to the important role of biological N2 -fixation and CO2 -fixation by the pentose phosphate pathway consistent with a population of cyanobacteria. Microscopic spheroidal grains of apatite (MSGA) occur in association with calcite microspar in microbial mats from stromatolite columns and with chert in the core of diagenetic apatite rosettes. Organic matter extracted from the stromatolitic phosphorites contains a range of molecular functional group (e.g. carboxylic acid, alcohol, and aliphatic hydrocarbons) as well as nitrile and nitro groups as determined from C- and N-XANES spectra. The presence of organic nitrogen was independently confirmed by a CN(-) peak detected by ToF-SIMS. Nanoscale petrography and geochemistry allow for a refinement of the formation model for the accretion and phototrophic growth of stromatolites. The original microbial biomass is inferred to have been dominated by cyanobacteria, which might be an important contributor of organic matter in shallow-marine phosphorites.

This paper reports a method for the determination of doping concentration profile in single and multi δ-doped GaAs layers on bevelled samples. The method is based on the recording and evaluation of micro-photoluminescence spectra along the bevelled structure. The values for the doping concentration profiles are in good agreement with those obtained by C–V, SIMS and Raman spectroscopy.

Objective and design: We have evaluated the effects of the broad-spectrum cysteine protease inhibitor E64 on allergic lung inflammation in the mouse ovalbumin model of human asthma. We have also characterised membrane-associated cathepsin enzyme activity on a range of cell types. Materials: Balb/C mice, E64 and CA074, various cell lines. Treatment: E64 was administered by subcutaneous minipump into ovalbumin-sensitised mice prior to intranasal ovalbumin challenge. The effect of E64 on ovalbumin-induced inflammation in vivo and ovalbumin-specific T cell proliferation in vitro and ex vivo was examined. Membrane-associated cathepsin activity on various cell types was measured. Results: E64 treatment (0.36-0.48 mg/day) led to a significant reduction in eosinophil numbers and lung weights in the mouse model. Histological examination of lungs confirmed the anti-inflammatory effect. E64 greatly reduced ovalbumin-specific T cell numbers in the lymph nodes draining the lung following intranasal challenge whilst an accumulation of these T cells was found in the 'priming' lymph nodes. An analysis of various cells involved in lymphocyte priming and migration revealed that monocytes, dendritic cells and endothelial cells express high levels of membrane-associated cathepsin B activity. Conclusions: Since E64 is not cell permeable and does not inhibit antigen-induced T cell proliferation in vitro or in vivo, the data indicate that membrane-associated cysteine proteases, possibly cathepsin B, may regulate T lymphocyte migration in vivo.

Lesion-induced inflammatory responses in both brain and spinal cord have recently become a topic of active investigation. Using C57BL/6J mice, we compared the tissue reaction in these two central nervous system (CNS) compartments with mechanical lesions of similar size involving both grey and white matter. This evaluation included the quantitative assessment of neutrophils, lymphocytes and activated macrophages/microglia, as well as astrocyte activation, upregulation of vascular cell adhesion molecules (ICAM-1, VCAM-1, PECAM) and the extent of blood-brain barrier (BBB) breakdown. Time points analysed post-lesioning included 1, 2, 4 and 7 days (as well as 10 and 14 days for the BBB). We found clear evidence that the acute inflammatory response to traumatic injury is significantly greater in the spinal cord than in the cerebral cortex. The numbers of both neutrophils and macrophages recruited to the lesion site were significantly higher in the spinal cord than in the brain, and the recruitment of these cells into the surrounding parenchyma was also more widespread in the cord. The area of BBB breakdown was substantially larger in the spinal cord and vascular damage persisted for a longer period. In the brain, as in spinal cord, the area to which neutrophils were recruited correlated well with the area of BBB breakdown. It will be of interest to determine the extent to which the infiltration of inflammatory cells contributes, either directly or indirectly, to the vascular permeability and secondary tissue damage or, conversely, to local tissue repair in the brain and the spinal cord.

The brain environment exerts a powerful influence on macrophage phenotype, as exemplified by microglia, but the mechanisms mediating this control are nuclear. Since adhesion molecules are known to transmit signals across cell membranes, we investigated adhesion receptors involved in macrophage interaction with brain tissue. We have demonstrated previously that macrophages adhere specifically to CNS neurones in an in vitro assay. Here we show that this adhesion is inhibited by lectins, including Griffonia simplicofolia isolectin B4 (GSI), which has been used as a microglial marker for many years. Adhesion is unaffected by antibodies to several known adhesion molecules but is markedly inhibited by a new monoclonal antibody: HB1. HB1 recognizes microglia in the normal brain and activated microglia and recruited monocytes during CNS pathology. It labels a subset of resident macrophages and recruited monocytes in other tissues. Using this antibody, we isolated a protein of about 110 kDa from macrophage cell lysates. This protein is recognized by GSI, providing the first evidence of a functional role for the antigen labelled by this lectin. Further study of the HB1 antigen may provide important information about the influence of the brain environment on the phenotype of monocytic cells.

Laminitis, a microvascular disease of the equine hoof leads to severe lameness. Exogenous iv 1-arginine and transdermal nitric oxide donors, such as GTN, applied to the pasterns improve lameness during acute laminitis. Near Infrared spectroscopy in an earlier study showed haemostasis and ischaemia in the hoof during acute laminitis, both were alleviated by 1-arginine. Quantitative NIRS in the present study shows that transdermal GTN increases blood flow in the equine hoof. It is concluded that glyceryl trinitrate enhances nitric oxide mediated perfusion within the equine hoof in normal and chronically laminitic horses and ponies.

Activation and proliferation of microglia are commonly described in the central nervous system after a wide range of insults, but the mechanisms that regulate their phenotype in vivo are still poorly understood. We have studied the effect that adrenalectomy and dexamethasone treatment have on the proliferation and activation of microglia during Wallerian degeneration of the optic nerve in BALB/c mice. We found that the onset and rate of microglia proliferation is independent of glucocorticoids. There was an increase in F4/80-positive cells 3 days after optic nerve crush, with a peak at 7 days, both in the optic nerve and its target, the superior colliculus. The numbers of F4/80-positive cells remained high up to 3 weeks after crush, the longest time point examined. We also found that up-regulation of F4/80 and the complement receptor type 3 and expression of major histocompatibility complex class II antigens were not affected by adrenalectomy or dexamethasone treatment. These observations show that, unlike microglia in vitro or peripheral macrophages, microglia do not readily respond to glucocorticoids, which could indicate a lack of or reduced expression of glucocorticoid receptor in these cells.

The potential for participation of the arginine-nitric oxide system in the aetiology of acute equine laminitis has been assessed. Nitric oxide (NO), produced by the action of NO synthase (NOS) on its substrate l-arginine, relaxes vascular smooth muscle to cause vasodilation. An attenuated normal vasodilatory tone may characterise the pathogenesis of acute equine laminitis. An intravenous infusion of 10% l-arginine in 0.9% saline caused vasodilatation in the hoof of a normal pony and immediate reperfusion of laminal tissues in an acutely laminitic pony, detected noninvasively by near infrared spectroscopy (NIRS), but the amino acid had little effect on systemic blood pressure. Treatment of acute laminitis with glyceryl trinitrate applied topically to the pasterns reduced the typical 'bounding pulses' in treated limbs, reduced lameness and lowered systemic blood pressure. Nitric oxide is likely to participate in the multifactorial pathogenesis of equine laminitis.

Macrophage recruitment into the distal nerve stump of the cut or crushed sciatic or saphenous nerves of C57BL/6J mice was reduced by prior whole body irradiation. This procedure was successful in keeping the numbers of cells stained with the mouse macrophage-specific antibody F4/80 to the levels found in unsectioned nerves. Quantitative image analysis of immunostained sections showed that the rate of loss of myelin basic protein was identical in nerves from irradiated and unirradiated mice up to 5 days but thereafter was slower in macrophage-deprived nerves. Similar analysis of semithin sections stained with toluidine blue detected more undegenerated myelin in the nerves from irradiated mice 10 days after operation. Quantitative counts made from electron micrographs of the sectioned nerves at 7 days also showed slightly less extensive myelin breakdown in the nerves from irradiated mice. Complete removal of myelin from some Schwann cells can occur without macrophages, but macrophages accelerate the removal of myelin in the later stages of Wallerian degeneration. It is concluded that there are two phases to the breakdown of myelin in peripheral nerves undergoing Wallerian degeneration: an initial stage entirely dependent on the activity of Schwann cells and a later stage dependent on both Schwann cells and the presence of macrophages.

Microglia, the resident macrophages of the central nervous system, are characterised by a highly specialized morphology and unusual antigenic phenotype. Microglia appear to be downregulated by their microenvironment when compared to other tissue macrophages. We have studied the microglia in brains of healthy, aged rats with a panel of monoclonal antibodies. We have found that microglia in the brains of these aged rats express antigens that are downregulated or absent from microglia of juvenile rats. The stimuli which give rise to this upregulated phenotype are not known. Age related changes in the phenotype of microglia should be taken into account when considering the possible role of microglia in neuropathological conditions.

Modern levitation furnaces are enabling melting and freezing of refractory materials like Al2O3 to be studied in depth with synchrotron radiation techniques. Whilst α-Al2O3 is a close packed Debye-like solid, liquid Al2O3 has smaller coordination numbers and the structure has network-like characteristics. Under contactless conditions, substantial under cooling can be achieved. Melting involves a significant decrease in density which is approximately recovered on recrystallization, both of which can be followed with high speed video imaging. Freezing occurs with a burst of energy — recalescence — which substantially raises the temperature momentarily. Using Rietveld refinement the density of α-Al2O3 and the mean square displacement of the average atom 〈μ2〉 can be followed up to the melting point and upon freezing using in situ X-ray diffraction. As melting is approached 〈μ2〉 for α-Al2O3 exceeds the harmonic approximation of the Lindemann–Galvarry law and for liquid Al2O3 above the melting point 〈μ2〉 appears to be greater still. On freezing from the undercooled state α-Al2O3 is initially decompressed with the T - P point falling on the melting curve extrapolated to negative pressures.

The use of incremental cost-effectiveness ratios based on quality-adjusted life-years (QALYs) as a critical determinant of what should be covered by a health system is a growing trend. This presents challenges when applied to rapidly evolving technologies. The case study here focuses on the example of drug-eluting stents and the four-year change in cost-effectiveness as determined by the U.K. National Institute for Health and Clinical Excellence (NICE). We contend that classic cost-effectiveness as a blunt instrument for determining what should be covered may lead to erroneous conclusions when a broader perspective and the impact on health outcomes and costs are considered.

We combine small-angle x-ray scattering (SAXS) and wide-angle x-ray scattering (WAXS) with aerodynamic levitation techniques to study in situ phase transitions in the liquid state under contactless conditions. At very high temperatures, yttria-alumina melts show a first-order transition, previously inferred from phase separation in quenched glasses. We show how the transition coincides with a narrow and reversible maximum in SAXS indicative of liquid unmixing on the nanoscale, combined with an abrupt realignment in WAXS features related to reversible shifts in polyhedral packing on the atomic scale. We also observed a rotary action in the suspended supercooled drop driven by repetitive transitions (a polyamorphic rotor) from which the reversible changes in molar volume (1.2 ± 0.2 cubic centimeters) and entropy (19 ± 4 joules mole –1 kelvin –1 ) can be estimated.

In a previous untargeted metabolomics study1, the metabolite 2-hexyl‐5‐ethyl-3-furansulfonic acid (HEFS, Figure 2) showed a toxicity induced reduction in earthworms. The results presented here focus on the specific localization of this metabolite in the invertebrate Lumbricus rubellus (widely distributed earthworm species) to receive a better understanding of its biological function. The application of Imaging Mass Spectrometry (IMS) techniques allows for whole-organism to sub-cellular metabolite localization. The use of MALDI in conjunction with an ultra-high resolution mass spectrometer with MS/MS capabilities makes in-situ identification of known and unknown metabolites feasible. In addition, TOF-SIMS with much higher spatial resolution but with a limited mass range gives information on detailed cellular distribution, making both methods complementary.

The resolution of the capacitance-voltage (C-V) technique on single- and multi-/spl delta/-doped GaAs is shown to be given by the breadth of dopant distribution. The experimental C-V profiles demonstrate that impurities are spatially localized on the length scale of the lattice constant. We present a technique of sample profiling by Raman spectroscopy with no depth limitation. It is based on the evaluation of the ratio of intensities of transverse and longitudinal optical phonons along a semiconductor-bevelled surface. Furthermore, the sharp distribution of dopants is assessed by the secondary-ion mass spectroscopy. The obtained results, the /spl delta/-doped layer location and spatial extent of dopants, are in agreement even though the measurements are probing different aspects.

The brain environment exerts a powerful influence on macrophage phenotype, as exemplified by microglia, but the mechanisms mediating this control are nuclear. Since adhesion molecules are known to transmit signals across cell membranes, we investigated adhesion receptors involved in macrophage interaction with brain tissue. We have demonstrated previously that macrophages adhere specifically to CNS neurones in an in vitro assay. Here we show that this adhesion is inhibited by lectins, including Griffonia simplicofolia isolectin B4 (GSI), which has been used as a microglial marker for many years. Adhesion is unaffected by antibodies to several known adhesion molecules but is markedly inhibited by a new monoclonal antibody: HB1. HB1 recognizes microglia in the normal brain and activated microglia and recruited monocytes during CNS pathology. It labels a subset of resident macrophages and recruited monocytes in other tissues. Using this antibody, we isolated a protein of about 110 kDa from macrophage cell lysates. This protein is recognized by GSI, providing the first evidence of a functional role for the antigen labelled by this lectin. Further study of the HB1 antigen may provide important information about the influence of the brain environment on the phenotype of monocytic cells.

Lesion-induced inflammatory responses in both brain and spinal cord have recently become a topic of active investigation. Using C57BL/6J mice, we compared the tissue reaction in these two central nervous system (CNS) compartments with mechanical lesions of similar size involving both grey and white matter. This evaluation included the quantitative assessment of neutrophils, lymphocytes and activated macrophages/microglia, as well as astrocyte activation, upregulation of vascular cell adhesion molecules (ICAM-1, VCAM-1, PECAM) and the extent of blood-brain barrier (BBB) breakdown. Time points analysed post-lesioning included 1, 2, 4 and 7 days (as well as 10 and 14 days for the BBB). We found clear evidence that the acute inflammatory response to traumatic injury is significantly greater in the spinal cord than in the cerebral cortex. The numbers of both neutrophils and macrophages recruited to the lesion site were significantly higher in the spinal cord than in the brain, and the recruitment of these cells into the surrounding parenchyma was also more widespread in the cord. The area of BBB breakdown was substantially larger in the spinal cord and vascular damage persisted for a longer period. In the brain, as in spinal cord, the area to which neutrophils were recruited correlated well with the area of BBB breakdown. It will be of interest to determine the extent to which the infiltration of inflammatory cells contributes, either directly or indirectly, to the vascular permeability and secondary tissue damage or, conversely, to local tissue repair in the brain and the spinal cord.

Different compartments in the central nervous system mount distinct inflammatory responses. The meninges and choroid plexus respond to pro-inflammatory stimuli in a manner reminiscent of a peripheral inflammatory response, whereas the brain parenchyma is refractory. Trauma-induced lesions in brain and in spinal cord are associated with leukocyte infiltration, blood-brain barrier (BBB) breakdown, and secondary tissue destruction. Unexpectedly, these phenomena are generally more pronounced in the parenchyma of the spinal cord than in the parenchyma of the brain. To investigate whether these differences between brain and spinal cord can be attributed, at least in part, to differing sensitivities to proinflammatory cytokines, we stereotactically injected recombinant rat (rr) TNFalpha or rrIL-1beta into the striatum or the spinal cord of Wistar rats. In the brain, the injection of rrTNFalpha failed to evoke BBB breakdown or leukocyte recruitment, whereas in the spinal cord injection of TNFalpha resulted in marked BBB breakdown and leukocyte recruitment. Similarly, the injection of rrIL-1beta into the brain parenchyma failed to induce BBB breakdown and gave rise to only minimal neutrophil recruitment, whereas the injection of rrIL-1beta into the spinal cord induced significant BBB breakdown and recruitment of neutrophils and lymphocytes. Thus, using a minimally invasive injection technique, equivalent in both circumstances, we have shown that there are marked differences in the inflammatory response between the brain parenchyma and spinal cord parenchyma. This observation has important implications for the treatment of spinal cord injuries.

When a peripheral nerve is damaged the severed axon undergoes Wallerian degeneration. The distal nerve is infiltrated by large numbers of monocyte-derived macrophages which participate in the phagocytosis of degenerating myelin. In other tissues, adhesion molecules play a crucial role in leukocyte recruitment during inflammation. Blood-borne cells enter damaged tissue by interacting with adhesion molecules expressed on activated endothelium. Having crossed the endothelium, leukocytes must adhere and migrate within the tissue. We investigated the adhesion molecules involved in both stages of the macrophage response to transection of one sciatic nerve of BALB/c mice. By injecting monoclonal antibodies in vivo, before and after peripheral nerve injury, we showed that intercellular adhesion molecule-1 (ICAM-1) and integrins alpha4beta1 (VLA-4) and alphaMbeta2 (type 3 complement receptor) are unlikely to be involved in the transendothelial migration of monocytes responding to peripheral nerve degeneration. We also studied the adhesion of macrophages within the endoneurium, using an in vitro adhesion assay. Macrophages showed much greater levels of adhesion to cryostat sections of transected nerves than to control nerves. This increased adhesion was partially inhibited by antibodies to the beta1-integrin chain, and more strongly inhibited by the extracellular matrix molecules fibronectin and collagen. Adhesion was unaffected by laminin-1 and by antibodies to other adhesion molecules, including alpha4beta1- and alpha5beta1-integrins. Thus we conclude that monocyte entry into a degenerating peripheral nerve is independent of alphaLbeta2/alphaMbeta2-ICAM-1 or alpha4beta1/VCAM-1 interactions, and that adhesion within the endoneurium is mediated in part by a beta1-integrin other than alpha4beta1 or alpha5beta1.

In adult rats, 50,000 units of recombinant interleukin-1 beta (IL-1 beta) injected into the brain parenchyma produced an intense meningitis and disruption of the blood-CSF barrier by 4 h. No increase in vascular permeability to horseradish peroxidase or leukocyte recruitment was observed at the site of injection. By contrast, in juvenile rats, 100 units of IL-1 beta injected into the striatum gave rise to a large increase in blood-brain barrier permeability and recruitment of polymorphonuclear neutrophils into the tissue around the injection site by 4 h. This effect was also accompanied by a marked meningitis. The injection of 100 units of IL-1 beta into neonatal (2-h-old) rats gave rise to an increase in permeability of vessels to serum proteins in the meninges, but no increase in vascular permeability was observed at the injection site. The IL-1 beta-induced increases in vessel permeability in the meninges, parenchyma, and choroid plexus were polymorphonuclear neutrophil dependent, since leukocyte depletion by irradiation or polymorphonuclear neutrophil anti-serum pre-treatment eliminated the response in the juvenile animals and in the adults. Seventy-five thousand units of murine tumour necrosis factor-alpha injected into the parenchyma of both adults and juvenile animals failed to induce an increase in blood-brain barrier permeability or polymorphonuclear neutrophil recruitment, but did give rise to a mild meningitis. These findings demonstrate clear differences in the responsiveness of different CNS compartments to IL-1 beta. Furthermore, while tumour necrosis factor-alpha and IL-1 beta might have been expected to exhibit similar proinflammatory effects in the CNS, this is not the case. We also show, for the first time, that age has a significant effect on the response to a cytokine. The "window of susceptibility' to an inflammatory stimulus in juvenile rats, if paralleled in humans, may be a major factor in the increased susceptibility of children to trauma or to infectious insults to the CNS.

Summary The present study applies near infrared spectroscopy (NIRS) to the haemodynamics of the pedal circulation in normal and laminitic horses. NIRS is a noninvasive technique which uses changes in light absorption at 4 wavelengths to provide information on the changes in cytochrome aa3 (cyt aa3) reduction-oxidation (redox) status, and changes in the tissue concentration of oxyhaemoglobin (O2Hb), deoxyhaemoglobin (HHb) and therefore total haemoglobin (tHb). Other studies have shown NIRS to be sensitive to changes in tissue oxygenation and perfusion in human cerebral and limb circulation. In this study, the NIRS sensor was applied to the dorsal surface of horses' hooves. Normal and laminitic animals (acute and chronic) were subjected to manoeuvres (cuff tourniquet; digital vessel occlusion at the palmar surface of the pastern; lifting of contralateral limb) predicted to change pedal haemodynamics. The procedures produced changes in pedal haemodynamics and oxygenation, which were similar to those observed in the ischaemic/reperfused human forearm. Laminitic differed from normal horses: return of HHb to baseline was slower and the change in cyt aa3 more rapid than normal in cases of chronic laminitis, taken to indicate reduced O2 stores as a result of compromised basal perfusion. In acute laminitis, baseline values did not fluctuate following any of the manoeuvres, suggesting haemostasis in the diseased hoof. NIRS is a useful noninvasive method to assess pedal vascular function in normal and laminitic horses.

Tiger snakes (Notechis scutatus) and lowland copperheads (Austrelaps superbus) are both large viviparous elapid snakes confined to the cooler, mesic regions of southern Australia. In spite of both species being common and widespread in the island state of Tasmania, no quantified studies on the trophic ecology of these two snakes from the main island has been published. During a two-year period we collected field data from 127 adult A. superbus and 74 adult N. scutatus from throughout eastern Tasmania. For both species, males were larger than females with respect to all measured parameters, including mass and head size. Reproduction in females was strongly seasonal and clutch size was not related to maternal body size. N. scutatus has a larger head than A. superbus and consequently ingests both small and large prey. N. scutatus in our study displayed the most catholic diet of any Australian elapid studied to date and consumed mammals (possum, bandicoot, antechinus, rats, mice), birds (fairy wrens), fish (eel, trout) and frogs. A. superbus shows a more specialist diet of large volumes of predominately ectothermic prey (frogs, lizards, snakes) even at maximal sizes and was more likely to contain ingested prey than specimens of N. scutatus. Distinctive rodent bite scars were common on N. scutatus but rare on A. superbus. The high frequency of rodent bite scars on N. scutatus further supports our findings of a primarily endothermic diet for mature specimens. We suggest that significant differences in head size, and hence diet, as well as a taxonomically diverse suite of potential prey in Tasmania allow both these large snakes to coexist in sympatry and avoid interspecific competitive exclusion.

We investigated the numbers, origin and phenotype of mononuclear phagocytes (macrophages/microglia) responding to Wallerian degeneration of the mouse optic nerve in order to compare it with the response to Wallerian degeneration in the PNS, already described. We found macrophage/microglial numbers elevated nearly four fold in the distal segments of crushed optic nerves and their projection areas in the contralateral superior colliculus 1 week after unilateral optic nerve crush. This relative increase in mononuclear phagocyte numbers compared well with the four-to-five-fold increases reported in the distal segments of transected saphenous or sciatic nerves. Moreover, maximum numbers are reached at 3, 5 and 7 days in the saphenous, sciatic and optic nerves respectively, suggesting that the very slow clearance of axonal debris and myelin in CNS undergoing Wallerian degeneration is not simply due to a slow or small mononuclear phagocyte response. The apparent delay in the response in the CNS occurs because the mononuclear phagocytes respond to the Wallerian degeneration of axons, which is slightly slower in the CNS than the PNS, rather than to events associated with the crush itself, such as the abolition of normal electrical activity in the distal segment. This was demonstrated by the protracted time course of the mononuclear phagocyte response in the distal segment following optic nerve crush in mice carrying the Wlds mutation which dramatically slows the rate at which the axons undergo Wallerian degeneration. By [3H]-Thymidine labelling or by blocking microglial proliferation by X-irradiation of the head prior to optic nerve crush, we showed that the majority of macrophages/microglia initiating the response to Wallerian degeneration were of local, CNS origin but these cells rapidly (from 3 days post crush) upregulate endocytic and phagocytic functional markers although they do not resemble rounded myelin-phagocytosing macrophages observed in degenerating peripheral nerves. We speculate that the poor clearance of myelin in CNS fibre tracts undergoing Wallerian degeneration compared to the PNS, in the face of a mononuclear phagocyte response which is similar in relative magnitude and time course, is because Schwann cells in degenerating peripheral nerves promptly modify their myelin sheaths such that they can be recognized and phagocytosed by macrophages, whilst in the CNS oligodendrocytes do not.

Brown tree snakes (Boiga irregularis) are medium to large colubrid snakes that are relatively common within the eastern and northern parts of tropical Australia. An invasive population on Guam in the western Pacific has resulted in B. irregularis being one of the most studied snakes on earth. However, no field studies have ever been conducted on Australian populations. During a seven-year period we collected data on 265 field-caught specimens in north Queensland. These snakes were from three populations and provided data on body sizes, activity times, food habits and reproduction. B. irregularis were found to attain larger body sizes in the Wet Tropics populations than in the Townsville and Magnetic Island populations. More snakes were encountered during the wet and warm season than during the dry and cool season. Sexual size dimorphism was not detected in any population. The diet included a wide range of vertebrates. Reproductive data were scant from the populations examined.

4 pages; International audience; The authors have studied the structural evolution of the fragile glass-forming liquid CaAl2O4 during supercooling from the stable liquid phase to the cold glass below Tg. The evolution is characterized by a sharpening of the first diffraction peak and a shortening of the average nearest-neighbor bond length around 1.25Tg, indicating an increase in the degree of both intermediate-range and short-range orders occurring close to the dynamical crossover temperature. The cooling curve developed a kink at this temperature, indicating a simultaneous change in thermodynamic properties.

Studies on species that attain very large body sizes provide a powerful opportunity to clarify the ecological correlates and consequences of body size, but logistical obstacles mean that most ‘giant’ species have attracted little field-based research. The Australian scrub python, Morelia kinghorni (= M. amethistina in earlier literature), is the largest Australian snake. Our three-year field study in the Tully River Gorge of tropical north-eastern Australia provides the first detailed ecological data on this species. Snakes aggregate in the gorge during the dry season for reproductive activities (combat, courtship and mating), and these aggregations consist primarily of large adult males. Wet-season samples from a nearby road contained more females, and more juvenile animals. Body temperatures of diurnally active pythons averaged 25.2°C, and were highly correlated with air and substrate temperatures. Larger snakes were cooler than smaller conspecifics, perhaps reflecting their slower heating rates. Recapture of marked individuals suggests that pythons of both sexes and all body sizes maintain fixed home ranges, as the distance from initial capture did not increase through time; most animals were recaptured

Carpet pythons (Morelia spilota) are large (to >4 m, 11 kg) non-venomous snakes that are widely distributed across mainland Australia. In many parts of their range, viable populations persist even in highly disturbed urban and suburban habitats. Over a six-year period, we collected 258 ‘nuisance’ pythons from two cities (Brisbane and Ipswich) in south-eastern Queensland. Most of these snakes were reported by members of the general public, often after the snakes had consumed domestic pets or cage-birds. We provide data on seasonal activity patterns, body sizes, sexual size dimorphism, reproduction and food habits of these snakes. Snakes were active and fed year-round, primarily on domestic and commensal birds and mammals. Dietary composition shifted with body size: one small snake consumed a lizard, intermediate-sized snakes took mostly mice, rats and parrots, and large snakes fed on larger items such as cats, brushtail possums and poultry. Adult male pythons engaged in combat bouts during the breeding season, and (perhaps as an adaptation to enhance success in such bouts) grew larger and were more heavy-bodied than conspecific females.

Editor—We read with interest the recent articles from the North of England evidence based guideline development project.1,2 We represent the Birmingham Clinical Effectiveness Group and admire the rigour with which these guidelines have been developed. The effort required to synthesise this amount of evidence cannot be underestimated, but has the effort been worth while? None of the guidelines provides new evidence, and, given the basic requirement for evidence based medicine to answer a clinically relevant question, their value is questionable. For example, it is well known that aspirin after myocardial infarction is beneficial.3 The challenge lies in increasing the use of aspirin in this clinical situation, in changing behaviour rather than simply improving knowledge. We wonder whether these guidelines will effect change such that aspirin use is increased. Similarly, it has been recognised for some time that the use of angiotensin converting enzyme inhibitors is beneficial for patients with cardiac failure, and the challenge remains the same. Maybe the effort and funding expended in reinforcing what is already known might have been better directed in trying to change clinicians’ behaviour in those areas where there is already an identifiable research to practice gap. We have shown that by adapting the North of England guidelines for angina for local use, the uptake of aspirin for patients who have had an infarction can be considerably increased, at fairly low cost, in inner city practice. Evidence needs to be synthesised, and these guidelines are useful source documents, but we believe that the primary focus of guideline research must now shift to implementation of extant knowledge rather than summarising existing research. The challenge does not seem to be in improving the knowledge base, but in improving the utilisation of that knowledge within real life clinical situations.

A simulated Magnox glass which is Mg- and Al- rich was subjected to aqueous corrosion in static mode with deionised water at 90 °C for 7 days and assessed using Cameca and Ion-ToF Secondary Ion Mass Spectrometry (SIMS). Depth profiling and ion imaging were done for both unleached and leached samples to reveal elemental distributions from the glass surface into the bulk. All the elements were distributed evenly for unleached glass. After leaching, depletion of alkali ions i.e. Na and Li was observed indicating the interdiffusion (ion exchange) process of the initial stage of leaching. Enrichment of Mg near the surface layer indicated precipitation of Mg-rich crystals at the near surface region.

Children are at greater risk than adults of permanent brain damage and mortality following head injury or infection [1-5]. Rodent models have demonstrated a 'window of susceptibility' in young animals during which the brain parenchyma is at greater risk of acute neutrophil-mediated breakdown of the blood-brain barrier [6-7]. The exact mechanism of this age-related susceptibility to brain inflammation has yet to be defined, but animal models have revealed that the potent pro-inflammatory cytokine interleukin-1beta (IL-1beta) initiates an intense acute neutrophil-mediated inflammatory response in the brains of young rats and mice that is not seen in adults [6]. Here, we demonstrate the rapid induction of CXC chemokines (which contain a Cys-X-Cys motif), in particular the cytokine-induced neutrophil chemoattractant CINC-1, following the intracerebral administration of IL-1beta. The CXC chemokines produced a more intense neutrophil response in young rats than in adults. The IL-1beta-induced blood-brain barrier breakdown in young rats could be attenuated by an anti-CINC-1 neutralising antibody. These results show that the immature central nervous system (CNS) is dramatically more susceptible to the chemotactic effects of CXC chemokines. Blocking the CXC chemokine activity associated with brain inflammation inhibits neutrophil-mediated blood-brain barrier damage and represents a significant therapeutic possibility.

(1954). Group Work in Public Recreation. Journal of the American Association for Health, Physical Education, and Recreation: Vol. 25, No. 3, pp. 35-36.