Central Nervous System Targets: Supraspinal Mechanisms of Analgesia

While the acute sensation of pain is protective, signaling the presence of actual or potential bodily harm, its persistence is unpleasant. When pain becomes chronic, it has limited evolutionarily advantage. Despite the differing nature of acute and chronic pain, a common theme is that sufferers seek pain relief. The possibility to medicate pain types as varied as a toothache or postsurgical pain reflects the diverse range of mechanism(s) by which pain-relieving "analgesic" therapies may reduce, eliminate, or prevent pain. Systemic application of an analgesic able to cross the blood-brain barrier can result in pain modulation via interaction with targets at different sites in the central nervous system. A so-called supraspinal mechanism of action indicates manipulation of a brain-defined circuitry. Pre-clinical studies demonstrate that, according to the brain circuitry targeted, varying therapeutic pain-relieving effects may be observed that relate to an impact on, for example, sensory and/or affective qualities of pain. In many cases, this translates to the clinic. Regardless of the brain circuitry manipulated, modulation of brain processing often directly impacts multiple aspects of nociceptive transmission, including spinal neuronal signaling. Consideration of supraspinal mechanisms of analgesia and ensuing pain relief must take into account nonbrain-mediated effects; therefore, in this review, the supraspinally mediated analgesic actions of opioidergic, anti-convulsant, and anti-depressant drugs are discussed. The persistence of poor treatment outcomes and/or side effect profiles of currently used analgesics highlight the need for the development of novel therapeutics or more precise use of available agents. Fully uncovering the complex biology of nociception, as well as currently used analgesic mechanism(s) and site(s) of action, will expedite this process

One size doesn't fit all: towards optimising the therapeutic potential of endogenous pain modulatory systems.

This is the final version. Available from Wolters Kluwer Health via the DOI in this record. Medical Research CouncilAcademy of Medical SciencesEngineering and Physical Sciences Research Counci

Dialysis residential care : a future dialysis service model

People with chronic kidney disease are ageing and have increasing co-morbidities. The current delivery of renal replacement therapy, dialysis and transplantation, needs to adjust to changing patient needs. This paper proposes a potential future service delivery model featuring a dialysis residential care facility and a care coordination focus. The residential care facility would be composed of four levels of care; high, hostel, independent and outpatient. The paper argues that this model may result in decreased morbidity, improved patient quality of life and may prove cost effective. Patients\u27 nutritional status, medication adherence and transport efficiency may be improved. We propose this model to stimulate further debate in order to meet the needs of current and future chronic kidney disease patients.<br /

Problems related to the integration of fault tolerant aircraft electronic systems

Problems related to the design of the hardware for an integrated aircraft electronic system are considered. Taxonomies of concurrent systems are reviewed and a new taxonomy is proposed. An informal methodology intended to identify feasible regions of the taxonomic design space is described. Specific tools are recommended for use in the methodology. Based on the methodology, a preliminary strawman integrated fault tolerant aircraft electronic system is proposed. Next, problems related to the programming and control of inegrated aircraft electronic systems are discussed. Issues of system resource management, including the scheduling and allocation of real time periodic tasks in a multiprocessor environment, are treated in detail. The role of software design in integrated fault tolerant aircraft electronic systems is discussed. Conclusions and recommendations for further work are included

The Detection of an Extremely Bright Fast Radio Burst in a Phased Array Feed Survey

We report the detection of an ultra-bright fast radio burst (FRB) from a modest, 3.4-day pilot survey with the Australian Square Kilometre Array Pathfinder. The survey was conducted in a wide-field fly's-eye configuration using the phased-array-feed technology deployed on the array to instantaneously observe an effective area of 160 deg^2, and achieve an exposure totaling 13200 deg^2 hr. We constrain the position of FRB 170107 to a region 8^'x 8^' in size (90% containment) and its fluence to be 58 ± 6 Jy ms. The spectrum of the burst shows a sharp cutoff above 1400 MHz, which could be due to either scintillation or an intrinsic feature of the burst. This confirms the existence of an ultra-bright (> 20 Jy ms) population of FRBs

Fast track children's hearing pilot: final report of the evaluation of the pilot

This report presents key findings of the evaluation of the Fast Track children’s hearings pilot in Scotland1. The research was undertaken by staff at the Universities of Glasgow, Stirling and Strathclyde between February 2003 and January 2005