Using stratified medicine to understand, diagnose, and treat neuropathic pain

Neuropathic pain (NeuP) is defined as pain arising from a lesion or disease of the somatosensory nervous system. NeuP is common, affecting approximately 6-8% of the general population and currently treatment is inadequate due to both poor drug efficacy and tolerability. Many different types of injury can cause neuropathic pain including genetic (e.g. SCN9A gain of function variants), metabolic (e.g. diabetic polyneuropathy), infective (e.g. HIV associated neuropathy, hepatitis), traumatic and toxic (e.g. chemotherapy induced neuropathy) causes. Such injurious events can impact on anatomically distinct regions of the somatosensory nervous system ranging from the terminals of nociceptive afferents (in small fiber neuropathy) to the thalamus (in post-stroke pain). Classification of neuropathic pain using etiology and location remains an important aspect of routine clinical practice; however, pain medicine is coming to the realization that we need more precision in this classification. The hope is that improved classification will lead to better understanding of risk, prognosis and optimal treatment of NeuP

Preparing for the 21st century economy.

After 30 years of university teaching and almost five years as a Reserve Bank president, Anthony M. Santomero knows the importance of education to a well-functioning economy. In recent years, he has seen several broad, long-term trends emerge-trends that will undoubtedly shape our environment and our economic fortunes. In "Preparing for the 21st Century Economy," he talks about two trends he deems to be of particular importance. First is the steady increase in international trade that has spilled over from the second half of the 20th century into the new millennium. Second is the revolution in information and communications technology that has spurred productivity and spawned a need for knowledge workers.International trade ; Information technology ; Education - Economic aspects

A Grammar for Reproducible and Painless Extract-Transform-Load Operations on Medium Data

Many interesting data sets available on the Internet are of a medium size---too big to fit into a personal computer's memory, but not so large that they won't fit comfortably on its hard disk. In the coming years, data sets of this magnitude will inform vital research in a wide array of application domains. However, due to a variety of constraints they are cumbersome to ingest, wrangle, analyze, and share in a reproducible fashion. These obstructions hamper thorough peer-review and thus disrupt the forward progress of science. We propose a predictable and pipeable framework for R (the state-of-the-art statistical computing environment) that leverages SQL (the venerable database architecture and query language) to make reproducible research on medium data a painless reality.Comment: 30 pages, plus supplementary material

The Animal Ethics of Temple Grandin: A Protectionist Analysis

This article brings animal protection theory to bear on Temple Grandin’s work, in her capacity both as a designer of slaughter facilities and as an advocate for omnivorism. Animal protection is a better term for what is often termed animal rights, given that many of the theories grouped under the animal rights label do not extend the concept of rights to animals. I outline the nature of Grandin’s system of humane slaughter as it pertains to cattle. I then outline four arguments Grandin has made defending meat-eating. On a protection-based approach, I argue, Grandin’s system of slaughter is superior to its traditional counterpart. Grandin’s success as a designer of humane slaughterhouses however is not matched by any corresponding success in offering a moral defence of meat-eating. Despite, or perhaps because of, the popularity of her work, Grandin’s arguments for continuing to eat animals are noteworthy only in how disappointing and rudimentary they are. If we can thank Grandin for making a difference in the lives of millions of farm animals, her work can also be criticized for not engaging the moral status of animals with the depth and rigor that it deserves

An investigation into central nervous system involvement in distal symmetrical diabetic neuropathy in type 1 diabetes mellitus.

Diabetes is a leading cause of peripheral neuropathy. It is the main initiating factor for foot ulceration and amputation resulting in considerable morbidity and remarkable consumption of scarce medical resources. Relatively little is known about the pathophysiology underlying DPN. Research into DPN has focused mainly on the peripheral nervous system (PNS) with central nervous system (CNS) involvement relatively overlooked. The studies undertaken have been designed to investigate CNS involvement in DPN. 1. Before embarking on spinal cord studies, I reviewed and modified the techniques employed in the pilot study to improve the precision and accuracy of cord cross sectional area measurements. These modifications were patiented to quality control studies, which are reported in Chapter 2. 2. I performed in-vivo cross-sectional magnetic resonance imaging of the cervical spine and reported evidence of spinal cord shrinkage (atrophy) in Painless DPN (Chapter 3). This study showed spinal cord atrophy to be an early phenomenon, present even in subclinical DPN. As the spinal cord is the caudal portion of the CNS, its involvement made us question whether the brain too may be involved. 3. Using MR spectroscopy I examined thalamic involvement in Painless DPN (Chapter 4). This deep brain nucleus is considered the gateway to all somatosensory information entering the brain, and responsible for modulation of sensory information prior to presentation to the cerebral cortex. I demonstrated thalamic biochemical abnormalities consistent with possible neuronal dysfunction in patients with Painless DPN. 4. The demonstration of thalamic neuronal dysfunction in DPN suggests that CNS involvement is not limited to the spinal cord but other important areas, responsible for somatosensory perception, may also be involved. Although the pathogenesis of thalamic involvement is unknown, it is likely that both vascular and metabolic factors that have been implicated in the pathogenesis of DPN are involved. In Chapter 4, I examined the possible role of metabolic factors in the pathogenesis of thalamic neuronal dysfunction in DPN. Using MR spectroscopy, I demonstrated a significant elevation in thalamic glutamine/glutamate in patients with diabetes. Glutamate is the most abundant excitatory neurotransmitter and implicated in various models of neuronal cell death. Astrocytes, which play an important role in glutamate/glutamine metabolism, were impaired in the thalamus of diabetic patients in this study. The combination of elevated glutamate and impaired thalamic astrocytes may provide a pathophysiological explanation for thalamic dysfunction in DPN. 5. In Chapter 5, an alternative hypothesis for thalamic neuronal dysfunction in DPN was tested. Using dynamic contrast enhanced MR perfusion imaging, I demonstrated that Painful DPN is associated with unique thalamic perfusion abnormalities. Intriguingly, these abnormalities were present in patients with Painful but not Painless DPN. 6. Finally, in Chapter 6, I conducted a randomised, double blind and placebo-control trial (RCT) comparing the efficacy and tolerability of sativex, a cannabis based medicinal extract (CBME), with placebo in the symptomatic treatment of painful DPN. This is the first ever RCT using a CBME in painful DPN. We report no significant difference in the primary outcome measure due to a massive placebo effect and that depression is a potential major confounder in such clinical trials