Pharmacological modulation of beta-endorphin in rat peritoneal macrophages.

The neuropeptide beta-endorphin is present in cells of the immune system, i.e., lymphocytes and monocytes, and its expression can be induced by immunological stimuli. In the present study, we showed that the increase of the serotoninergic availability induces an increase of beta-endorphin concentrations in rat peritoneal macrophages that is blunted by the administration of serotonin receptor antagonists. A significant increase of beta-endorphin concentrations is also evident after blocking the dopaminergic receptors, whereas a dopaminergic agonist decreases the concentrations of the peptide. Our data are consistent with a similar modulation of beta-endorphin concentrations in central nervous system and in immune cells, e.g., rat peritoneal macrophages

Revisiting the frequency domain: the multiple and partial coherence of cerebral blood flow velocity in the assessment of dynamic cerebral autoregulation

Despite advances in modelling dynamic autoregulation, only part of the variability of cerebral blood flow velocity (CBFV) in the low frequency range has been explained. We investigate whether a multivariate representation can be used for this purpose. Pseudorandom sequences were used to inflate thigh cuffs and to administer 5% CO2. Multiple and partial coherence were estimated, using arterial blood pressure (ABP), end-tidal CO2 (EtCO2) and resistance area product as input and CBFV as output variables. The inclusion of second and third input variables increased the amount of CBFV variability that can be accounted for (p  <  10−4 in both cases). Partial coherence estimates in the low frequency range (<0.07 Hz) were not influenced by the use of thigh cuffs, but CO2 administration had a statistically significant effect (p  <  10−4 in all cases). We conclude that the inclusion of additional inputs of a priori known physiological significance can help account for a greater amount of CBFV variability and may represent a viable alternative to more conventional non-linear modelling. The results of partial coherence analysis suggest that dynamic autoregulation and CO2 reactivity are likely to be the result of different physiological mechanisms

Coherent averaging of pseudorandom binary stimuli: is the dynamic cerebral autoregulatory response symmetrical?

Objective: Previous studies on cerebral autoregulation have shown the existence of hemispheric symmetry, which may be altered in stroke and traumatic brain injury. There is a paucity of data however on whether the response is symmetrical between those disturbances that cause cerebral hyperperfusion, to those that cause hypoperfusion. Our aim was to investigate whether the responses of cerebral autoregulation to haemodynamic stimuli of different directions are symmetrical. &#13; Approach: Using a previously described assessment method, we employed coherent averaging of the cerebral blood flow velocity (CBFV) responses to thigh cuff inflation and deflation, as driven by pseudorandom binary sequences, whilst simultaneously altering the inspired CO2. The symmetry of the autoregulatory response was assessed with regards to two parameters, its speed and gain. Using the first harmonic method, critical closing pressure (CrCP) and resistance area product (RAP) were estimated, and the gain of the autoregulatory response was calculated by performing linear regression between the coherent averages of arterial blood pressure (ABP) and CBFV, ABP and CrCP and finally ABP and RAP. A two-way repeated measures ANOVA was used to assess for the effect of the direction of change in ABP and the method of CO2 administration. &#13; Main results: Our results suggest that whilst the direction of ABP change does not have a significant effect, the effect of CO2 administration method is highly significant (p&lt;10-4). &#13; Significance: This is the first report to report to demonstrate the symmetry of the autoregulatory response to stimuli of different directions as well as the short term dynamics of RAP and CrCP under intermittent and constant hypercapnia. As haemodynamic stimulus direction does not appear to have an influence, our findings validate previous work done using different assessment methods

East Midlands Research into Ageing Network (EMRAN) Discussion Paper Series

Academic geriatric medicine in Leicester . There has never been a better time to consider joining us. We have recently appointed a Professor in Geriatric Medicine, alongside Tom Robinson in stroke and Victoria Haunton, who has just joined as a Senior Lecturer in Geriatric Medicine. We have fantastic opportunities to support students in their academic pursuits through a well-established intercalated BSc programme, and routes on through such as ACF posts, and a successful track-record in delivering higher degrees leading to ACL post. We collaborate strongly with Health Sciences, including academic primary care. See below for more detail on our existing academic set-up. Leicester Academy for the Study of Ageing We are also collaborating on a grander scale, through a joint academic venture focusing on ageing, the ‘Leicester Academy for the Study of Ageing’ (LASA), which involves the local health service providers (acute and community), De Montfort University; University of Leicester; Leicester City Council; Leicestershire County Council and Leicester Age UK. Professors Jayne Brown and Simon Conroy jointly Chair LASA and have recently been joined by two further Chairs, Professors Kay de Vries and Bertha Ochieng. Karen Harrison Dening has also recently been appointed an Honorary Chair. LASA aims to improve outcomes for older people and those that care for them that takes a person-centred, whole system perspective. Our research will take a global perspective, but will seek to maximise benefits for the people of Leicester, Leicestershire and Rutland, including building capacity. We are undertaking applied, translational, interdisciplinary research, focused on older people, which will deliver research outcomes that address domains from: physical/medical; functional ability, cognitive/psychological; social or environmental factors. LASA also seeks to support commissioners and providers alike for advice on how to improve care for older people, whether by research, education or service delivery. Examples of recent research projects include: ‘Local History Café’ project specifically undertaking an evaluation on loneliness and social isolation; ‘Better Visits’ project focused on improving visiting for family members of people with dementia resident in care homes; and a study on health issues for older LGBT people in Leicester. Clinical Geriatric Medicine in Leicester We have developed a service which recognises the complexity of managing frail older people at the interface (acute care, emergency care and links with community services). There are presently 17 consultant geriatricians supported by existing multidisciplinary teams, including the largest complement of Advance Nurse Practitioners in the country. Together we deliver Comprehensive Geriatric Assessment to frail older people with urgent care needs in acute and community settings. The acute and emergency frailty units – Leicester Royal Infirmary This development aims at delivering Comprehensive Geriatric Assessment to frail older people in the acute setting. Patients are screened for frailty in the Emergency Department and then undergo a multidisciplinary assessment including a consultant geriatrician, before being triaged to the most appropriate setting. This might include admission to in-patient care in the acute or community setting, intermediate care (residential or home based), or occasionally other specialist care (e.g. cardiorespiratory). Our new emergency department is the county’s first frail friendly build and includes fantastic facilities aimed at promoting early recovering and reducing the risk of hospital associated harms. There is also a daily liaison service jointly run with the psychogeriatricians (FOPAL); we have been examining geriatric outreach to oncology and surgery as part of an NIHR funded study. We are home to the Acute Frailty Network, and those interested in service developments at the national scale would be welcome to get involved. Orthogeriatrics There are now dedicated hip fracture wards and joint care with anaesthetists, orthopaedic surgeons and geriatricians. There are also consultants in metabolic bone disease that run clinics. Community work Community work will consist of reviewing patients in clinic who have been triaged to return to the community setting following an acute assessment described above. Additionally, primary care colleagues refer to outpatients for sub-acute reviews. You will work closely with local GPs with support from consultants to deliver post-acute, subacute, intermediate and rehabilitation care services. Stroke Medicine 24/7 thrombolysis and TIA services. The latter is considered one of the best in the UK and along with the high standard of vascular surgery locally means one of the best performances regarding carotid intervention

Systemic administration of human adipose-derived stem cells reverts nociceptive hypersensitivity in an experimental model of neuropathy

Over the last decade it has been proved that Mesenchymal Stem Cells (MSCs) elicit anti-inflammatory effects. Mesenchymal Stem Cells from adipose tissue (hASCs) differentiate into cells of mesodermal lineage and trans-differentiate into ectodermal origin cells. Though there are various etiologies to chronic pain, one common feature is that painful states are associated with increased inflammation. We believe in hASCs as an therapeutic tool also in pathologies involving neuro-inflammation and neuronal-tissue damage. We have investigated the effect of hASCs injected in a model of neuropathic pain (mouse sciatic nerve Chronic Constriction Injury-CCI). hASCs from 5 donors were characterized, and no major differences were depicted. hASCs were cryopreserved and grown on demand. 1x106, 3x106 and 6x106 hASCs were intravenously injected into normal immunocompetent mice. No mouse died and no macroscopic toxicity or behavioral changes were observed, confirming the safety of hASCs. hASCs, i.v. injected into C57BL/6 mice, when the neuropathic pain was already established, induced a significant reduction in mechanical allodynia and a complete reversion of thermal hyperalgesia in a dose response fashion, already 1 day after administration. Moreover, the hASCs effect can be boosted by repeated administrations, allowing a prolonged therapeutic effect. Treatment decreased the level of the CCI-induced pro-inflammatory cytokine IL-1\u3b2 and activated the anti-inflammatory cytokine IL-10 in the lesioned nerve. hASC treatment also restored normal inducible Nitric Oxide Synthase (iNOS) expression in the CCI animals spinal cord. Our data suggest that hASCs are worthy further studies as anti-inflammatory therapy in the treatment of neuropathic pain or chronic inflammatory diseases

The connected prescription for form factors in twistor space

We would like to thank Paul Heslop and Brenda Penante for very interesting discussions. This work was supported by the Science and Technology Facilities Council (STFC) Consolidated Grant ST/L000415/1 “String theory, gauge theory & duality”. The work of EH was supported by an STFC quota studentship

From Driving Simulation to Virtual Reality

Driving simulation from the very beginning of the advent of VR technology uses the very same technology for visualization and similar technology for head movement tracking and high end 3D vision. They also share the same or similar difficulties in rendering movements of the observer in the virtual environments. The visual-vestibular conflict, due to the discrepancies perceived by the human visual and vestibular systems, induce the so-called simulation sickness, when driving or displacing using a control device (ex. Joystick). Another cause for simulation sickness is the transport delay, the delay between the action and the corresponding rendering cues. Another similarity between driving simulation and VR is need for correct scale 1:1 perception. Correct perception of speed and acceleration in driving simulation is crucial for automotive experiments for Advances Driver Aid System (ADAS) as vehicle behavior has to be simulated correctly and anywhere where the correct mental workload is an issue as real immersion and driver attention is depending on it. Correct perception of distances and object size is crucial using HMDs or CAVEs, especially as their use is frequently involving digital mockup validation for design, architecture or interior and exterior lighting. Today, the advents of high resolution 4K digital display technology allows near eye resolution stereoscopic 3D walls and integrate them in high performance CAVEs. High performance CAVEs now can be used for vehicle ergonomics, styling, interior lighting and perceived quality. The first CAVE in France, built in 2001 at Arts et Metiers ParisTech, is a 4 sided CAVE with a modifiable geometry with now traditional display technology. The latest one is Renault’s 70M 3D pixel 5 sides CAVE with 4K x 4K walls and floor and with a cluster of 20 PCs. Another equipment recently designed at Renault is the motion based CARDS driving simulator with CAVE like 4 sides display system providing full 3D immersion for the driver. The separation between driving simulation and digital mockup design review is now fading though different uses will require different simulation configurations. New application domains, such as automotive AR design, will bring combined features of VR and driving simulation technics, including CAVE like display system equipped driving simulators

Pyrolysis Gas Composition for a Phenolic Impregnated Carbon Ablator Heatshield

Published physical properties of phenolic impregnated carbon ablator (PICA) are compiled, and the composition of the pyrolysis gases that form at high temperatures internal to a heatshield is investigated. A link between the composition of the solid resin, and the composition of the pyrolysis gases created is provided. This link, combined with a detailed investigation into a reacting pyrolysis gas mixture, allows a consistent, and thorough description of many of the physical phenomena occurring in a PICA heatshield, and their implications, to be presented

Towards analytical typologies of plot systems: quantitative profile of five European cities

The importance of the plot (also referred to as ‘property’) as one of the fundamental elements of urban form is well recognized within the field of urban morphology. Despite the fact that it is often described as the basic element in the pattern of land divisions, which are essential as organizational frameworks for urban form, studies offering comprehensive descriptions and classifications of plot systems are quite scant. The aim of the paper is to introduce a classification of plot systems into typologies based on five European cities, in order to distinguish particular spatial differences and similarities in terms of their plot structure. The proposed typologies are developed using unsupervised k-means cluster analysis based on numeric attributes derived from central theories in urban morphology. The introduced typologies are essentially configurational, allowing collective systematic properties of plot systems to be captured. Numeric attributes include plot differentiation (or plot size), plot frontage and compactness ratio, corresponding to essential qualities of plot systems such as the capacity to carry differences in space, the ability to operate as interface between street and building and providing a framework for evolution of built form over time. All three attributes are translated into configurational measures in order to capture the context of the plot system, rather than the parameters of individual plots. The combination of these deductively defined variables with algorithmically defined classification methods results in seven plot types that can be used to scale up traditional urban morphological analysis to whole city regions and conduct substantial comparison of patterns within, but also between these regions. Further, it also makes it possible to describe commonly recognized plot patterns and discover new ones