Use of functional imaging across clinical phases in CNS drug development

The use of novel brain biomarkers using nuclear magnetic resonance imaging holds potential of making central nervous system (CNS) drug development more efficient. By evaluating changes in brain function in the disease state or drug effects on brain function, the technology opens up the possibility of obtaining objective data on drug effects in the living awake brain. By providing objective data, imaging may improve the probability of success of identifying useful drugs to treat CNS diseases across all clinical phases (I–IV) of drug development. The evolution of functional imaging and the promise it holds to contribute to drug development will require the development of standards (including good imaging practice), but, if well integrated into drug development, functional imaging can define markers of CNS penetration, drug dosing and target engagement (even for drugs that are not amenable to positron emission tomography imaging) in phase I; differentiate objective measures of efficacy and side effects and responders vs non-responders in phase II, evaluate differences between placebo and drug in phase III trials and provide insights into disease modification in phase IV trials

Scenario evaluation through Mine Schedule Optimisation

The Schedule Optimisation Tool (SOT) is a software that identifies the sequence (schedule) of mine development and the ore production activities that maximise the Net Present Value (NPV). A case study exercise in a live mine planning process found that SOT added over a hundred million dollars of value to the orebody. SOT has been enhanced to allow automated generation and evaluation of mine design parameters. The first enhancement allows the automated evaluation of schedules over a range of operational resource constraints. Heuristics can be used to seed the starting point of the search; for example, by prioritising production from specific stopes based on their mineral grades. The second enhancement allows a user‐specified ranking to be applied as a seeding heuristic. A third enhancement allows automated application of sequencing rules for primary and secondary stopes. SOT provides substantial assistance to the mine planner, allowing for strategic decisions based on a thorough evaluation of mine design parameters

Operation of a LAr-TPC equipped with a multilayer LEM charge readout

A novel detector for the ionization signal in a single phase LAr-TPC, based on the adoption of a multilayer Large Electron Multiplier (LEM) replacing the traditional anodic wire arrays, has been experimented in the ICARINO test facility at the INFN Laboratories in Legnaro. Cosmic muon tracks were detected allowing the measurement of energy deposition and a first determination of the signal to noise ratio. The analysis of the recorded events demonstrated the 3D reconstruction capability of ionizing events in this device in liquid Argon, collecting a fraction of about 90% of the ionization signal with signal to noise ratio similar to that measured with more traditional wire chambersComment: 9 pages, 7 Figure

A hardware implementation of Region-of-Interest selection in LAr-TPC for data reduction and triggering

Large Liquid Argon TPC detectors in the range of multikton mass for neutrino and astroparticle physics require the extraction and treatment of signals from some 105 wires. In order to enlarge the throughtput of the DAQ system an on-line lossless data compression has been realized reducing almost a factor 4 the data flow. Moreover a trigger system based on a new efficient on-line identification algorithm of wire hits was studied, implemented on the actual ICARUS digital read- out boards and fully tested on the ICARINO LAr-TPC facility operated at LNL INFN Laboratory with cosmic-rays. Capability to trigger isolated low energy events down to 1 MeV visible energy was also demonstrated.Comment: 26 pages, 26 Figure; to be submitted to JINS

Neuroimaging revolutionizes therapeutic approaches to chronic pain

An understanding of how the brain changes in chronic pain or responds to pharmacological or other therapeutic interventions has been significantly changed as a result of developments in neuroimaging of the CNS. These developments have occurred in 3 domains : (1) Anatomical Imaging which has demonstrated changes in brain volume in chronic pain; (2) Functional Imaging (fMRI) that has demonstrated an altered state in the brain in chronic pain conditions including back pain, neuropathic pain, and complex regional pain syndromes. In addition the response of the brain to drugs has provided new insights into how these may modify normal and abnormal circuits (phMRI or pharmacological MRI); (3) Chemical Imaging (Magnetic Resonance Spectroscopy or MRS) has helped our understanding of measures of chemical changes in chronic pain. Taken together these three domains have already changed the way in which we think of pain – it should now be considered an altered brain state in which there may be altered functional connections or systems and a state that has components of degenerative aspects of the CNS