A Selective Role for alpha3 Subunit Glycine Receptors in Inflammatory Pain.

GlyR alpha3 has previously been found to play a critical role in pain hypersensitivity following spinal PGE(2) injection, complete Freund's adjuvant (CFA) and zymosan induced peripheral inflammation. In this study, although all models displayed typical phenotypic behaviours, no significant differences were observed when comparing the pain behaviours of Glra3(-/-) and wild-type littermates following the injection of capsaicin, carrageenan, kaolin/carrageenan or monosodium iodoacetate, models of rheumatoid and osteoarthritis, respectively. However, clear differences were observed following CFA injection (p < 0.01). No significant differences were observed in the pain behaviours of Glra3(-/-) and wild-type littermates following experimentally induced neuropathic pain (partial sciatic nerve ligation). Similarly, Glra3(-/-) and wild-type littermates displayed indistinguishable visceromotor responses to colorectal distension (a model of visceral pain) and in vivo spinal cord dorsal horn electrophysiology revealed no differences in responses to multimodal suprathreshold stimuli, intensities which equate to higher pain scores such as those reported in the clinic. These data suggest that apart from its clear role in CFA- and zymosan-induced pain sensitisation, hypersensitivity associated with other models of inflammation, neuropathy and visceral disturbances involves mechanisms other than the EP2 receptor - GlyR alpha3 pathway

Implementing the Flinders Model of self-management support with Aboriginal people who have diabetes: findings from a pilot study

Programs to increase patients' capacity to manage their chronic disease are growing in popularity with policy makers, health professionals and the general public. However, until this pilot in regional South Australia, Indigenous people rarely participated in such programs. The pilot included extensive consultations with the Indigenous community, ownership of the program by an Aboriginal community-controlled health service, and a key role for Aboriginal and Torres Strait Islander Health Workers as the main coordinators of self-management support. The result was that 60 Aboriginal people participated and achieved notable improvements in health outcomes and personal goals. This pilot demonstrates that mainstream programs are relevant for Aboriginal communities as long as Aboriginal people lead the adaptation process

Chronic disease self-management in Aboriginal communities: towards a sustainable program of care in rural communities

Bundoora, VI

Nitrogen forms affect root structure and water uptake in the hybrid poplar

The study analyses the effects of two different forms of nitrogen fertilisation (nitrate and ammonium) on root structure and water uptake of two hybrid poplar (Populus maximowiczii x P. balsamifera) clones in a field experiment. Water uptake was studied using sap flow gauges on individual proximal roots and coarse root structure was examined by excavating 18 whole-root systems. Finer roots were scanned and analyzed for architecture. Nitrogen forms did not affect coarse-root system development, but had a significant effect on fine-root development. Nitrate-treated trees presented higher fine:coarse root ratios and higher specific root lengths than control or ammonium treated trees. These allocation differences affected the water uptake capacity of the plants as reflected by the higher sapflow rate in the nitrate treatment. The diameter of proximal roots at the tree base predicted well the total root biomass and length. The diameter of smaller lateral roots also predicted the lateral root mass, length, surface area and the number of tips. The effect of nitrogen fertilisation on the fine root structure translated into an effect on the functioning of the fine roots forming a link between form (architecture) and function (water uptake)

Mindfulness training modulates value signals in ventromedial prefrontal cortex through input from insular cortex

Neuroimaging research has demonstrated that ventromedial prefrontal cortex (vmPFC) encodes value signals that can be modulated by top-down cognitive input such as semantic knowledge, price incentives, and monetary favors suggesting that such biases may have an identified biological basis. It has been hypothesized that mindfulness training (MT) provides one path for gaining control over such top-down influences; yet, there have been no direct tests of this hypothesis. Here, we probe the behavioral and neural effects of MT on value signals in vmPFC in a randomized longitudinal design of 8weeks of MT on an initially naïve subject cohort. The impact of this within-subject training was assessed using two paradigms: one that employed primary rewards (fruit juice) in a simple conditioning task and another that used a well-validated art-viewing paradigm to test bias of monetary favors on preference. We show that MT behaviorally censors the top-down bias of monetary favors through a measurable influence on value signals in vmPFC. MT also modulates value signals in vmPFC to primary reward delivery. Using a separate cohort of subjects we show that 8weeks of active control training (ACT) generates the same behavioral impact also through an effect on signals in the vmPFC. Importantly, functional connectivity analyses show that value signals in vmPFC are coupled with bilateral posterior insula in the MT groups in both paradigms, but not in the ACT groups. These results suggest that MT integrates interoceptive input from insular cortex in the context of value computations of both primary and secondary rewards

Evaluating the successful implementation of evidence into practice using the PARiHS framework : theoretical and practical challenges

Background The PARiHS framework (Promoting Action on Research Implementation in Health Services) has proved to be a useful practical and conceptual heuristic for many researchers and practitioners in framing their research or knowledge translation endeavours. However, as a conceptual framework it still remains untested and therefore its contribution to the overall development and testing of theory in the field of implementation science is largely unquantified. Discussion This being the case, the paper provides an integrated summary of our conceptual and theoretical thinking so far and introduces a typology (derived from social policy analysis) used to distinguish between the terms conceptual framework, theory and model – important definitional and conceptual issues in trying to refine theoretical and methodological approaches to knowledge translation. Secondly, the paper describes the next phase of our work, in particular concentrating on the conceptual thinking and mapping that has led to the generation of the hypothesis that the PARiHS framework is best utilised as a two-stage process: as a preliminary (diagnostic and evaluative) measure of the elements and sub-elements of evidence (E) and context (C), and then using the aggregated data from these measures to determine the most appropriate facilitation method. The exact nature of the intervention is thus determined by the specific actors in the specific context at a specific time and place. In the process of refining this next phase of our work, we have had to consider the wider issues around the use of theories to inform and shape our research activity; the ongoing challenges of developing robust and sensitive measures; facilitation as an intervention for getting research into practice; and finally to note how the current debates around evidence into practice are adopting wider notions that fit innovations more generally. Summary The paper concludes by suggesting that the future direction of the work on the PARiHS framework is to develop a two-stage diagnostic and evaluative approach, where the intervention is shaped and moulded by the information gathered about the specific situation and from participating stakeholders. In order to expedite the generation of new evidence and testing of emerging theories, we suggest the formation of an international research implementation science collaborative that can systematically collect and analyse experiences of using and testing the PARiHS framework and similar conceptual and theoretical approaches. We also recommend further refinement of the definitions around conceptual framework, theory, and model, suggesting a wider discussion that embraces multiple epistemological and ontological perspectives

Characterizing the hypertensive cardiovascular phenotype in the UK Biobank

Aims: To describe hypertension-related cardiovascular magnetic resonance (CMR) phenotypes in the UK Biobank considering variations across patient populations. Methods and results: We studied 39 095 (51.5% women, mean age: 63.9 ± 7.7 years, 38.6% hypertensive) participants with CMR data available. Hypertension status was ascertained through health record linkage. Associations between hypertension and CMR metrics were estimated using multivariable linear regression adjusting for major vascular risk factors. Stratified analyses were performed by sex, ethnicity, time since hypertension diagnosis, and blood pressure (BP) control. Results are standardized beta coefficients, 95% confidence intervals, and P-values corrected for multiple testing. Hypertension was associated with concentric left ventricular (LV) hypertrophy (increased LV mass, wall thickness, concentricity index), poorer LV function (lower global function index, worse global longitudinal strain), larger left atrial (LA) volumes, lower LA ejection fraction, and lower aortic distensibility. Hypertension was linked to significantly lower myocardial native T1 and increased LV ejection fraction. Women had greater hypertension-related reduction in aortic compliance than men. The degree of hypertension-related LV hypertrophy was greatest in Black ethnicities. Increasing time since diagnosis of hypertension was linked to adverse remodelling. Hypertension-related remodelling was substantially attenuated in hypertensives with good BP control. Conclusion: Hypertension was associated with concentric LV hypertrophy, reduced LV function, dilated poorer functioning LA, and reduced aortic compliance. Whilst the overall pattern of remodelling was consistent across populations, women had greater hypertension-related reduction in aortic compliance and Black ethnicities showed the greatest LV mass increase. Importantly, adverse cardiovascular remodelling was markedly attenuated in hypertensives with good BP control

Effects of melting, subduction-related metasomatism, and sub-solidus equilibration on the distribution of water contents in the mantle beneath the Rio Grande Rift

The distribution of water in the upper mantle plays a crucial role in the Earth's deep water cycle, magmatism, and plate tectonics. To better constrain how these large-scale geochemical systems operate, peridotite and pyroxenite mantle xenoliths from Kilbourne Hole (KH) and Rio Puerco (RP) along the Rio Grande Rift (NM, USA) were analyzed for water, and major and trace element contents. These xenoliths sample a lithosphere whose composition was influenced by subduction and rifting, and can be used to examine the effects of melting, metasomatism, and sub-solidus equilibration on the behavior of water. The first result is that in KH xenoliths, olivines underwent negligible H loss during xenolith ascent, i.e. preserved their mantle water contents. These olivine water contents are used to calculate mantle viscosities of 0.5–184 · 1021 Pa·s. These viscosity values are more than 40 times higher than those of the asthenosphere and show that KH peridotites represent samples from the lithosphere. The preservation of olivine water contents is exceptional for off-cratonic xenoliths, and the KH peridotites provide the first estimate of the average concentration of water in Phanerozoic continental mantle lithosphere at 81 ± 30 ppm H2O. The mantle lithosphere beneath the Rio Grande rift is nevertheless heterogeneous with water contents ranging from <0.5 to 120 ppm H2O in peridotites and from 227 to 400 ppm H2O in pyroxenites. A composite KH xenolith of a harzburgite cross-cut by a clinopyroxenite vein shows this heterogeneity at the cm scale. The second contribution of this study stems from the majority of the KH peridotites and two of the RP peridotites having major and trace elements that can be explained by partial melting without any need to invoke metasomatic processes. This allows to show that, prior to modelling the water content variation of each peridotite mineral during melting, a correction for sub-solidus equilibration has to be applied to the water contents of the minerals. Sub-solidus equilibration also provides an explanation for the discrepancy between the clinopyroxene/orthopyroxene ratio of water contents in natural peridotites worldwide and in laboratory experiments on water partitioning in peridotite minerals. Finally, the cryptically metasomatized peridotites, rare at KH and abundant at RP, as well as the pyroxenites, permit to decipher the origin and water contents of the metasomatic melts that affected the continental lithosphere beneath the Rio Grande Rift. Trace element modelling of the metasomatized KH and RP peridotites are consistent with metasomatism via melts that are of subduction origin. Melts in equilibrium with peridotites contain more water at RP (∼1 wt.% H2O) than at KH (∼0.5 wt.% H2O), although this did not result in a more water-rich mantle lithosphere at RP. Rio Puerco lies within the northern Rio Grande rift, proposed to have been affected by a flat slab subduction, which may explain the more hydrous and extensive metasomatism compared to the south, where KH is located

Sexual Selection and the Evolution of Brain Size in Primates

Reproductive competition among males has long been considered a powerful force in the evolution of primates. The evolution of brain size and complexity in the Order Primates has been widely regarded as the hallmark of primate evolutionary history. Despite their importance to our understanding of primate evolution, the relationship between sexual selection and the evolutionary development of brain size is not well studied. The present research examines the evolutionary relationship between brain size and two components of primate sexual selection, sperm competition and male competition for mates. Results indicate that there is not a significant relationship between relative brain size and sperm competition as measured by relative testis size in primates, suggesting sperm competition has not played an important role in the evolution of brain size in the primate order. There is, however, a significant negative evolutionary relationship between relative brain size and the level of male competition for mates. The present study shows that the largest relative brain sizes among primate species are associated with monogamous mating systems, suggesting primate monogamy may require greater social acuity and abilities of deception