Pioneers in CNS inhibition: 2. Charles Sherrington and John Eccles on inhibition in spinal and supraspinal structures

This article reviews the contributions of the English neurophysiologist, Charles Scott Sherrington [1857–1952], and his Australian PhD trainee and collaborator, John Carew Eccles [1903–1997], to the concept of central inhibition in the spinal cord and brain. Both were awarded Nobel Prizes; Sherrington in 1932 for “discoveries regarding the function of neurons,” and Eccles in 1963 for “discoveries concerning the ionic mechanisms involved in excitation and inhibition in central portions of the nerve cell membrane.” Both spoke about central inhibition at their Nobel Prize Award Ceremonies. The subsequent publications of their talks were entitled “Inhibition as a coordinative factor” and “The ionic mechanism of postsynaptic inhibition”, respectively. Sherrington's work on central inhibition spanned 41 years (1893–1934), and for Eccles 49 years (1928–1977). Sherrington first studied central inhibition by observing hind limb muscle responses to electrical (peripheral nerve) and mechanical (muscle) stimulation. He used muscle length and force measurements until the early 1900s and electromyography in the late 1920s. Eccles used these techniques while working with Sherrington, but later employed extracellular microelectrode recording in the spinal cord followed in 1951 by intracellular recording from spinal motoneurons. This considerably advanced our understanding of central inhibition. Sherrington's health was poor during his retirement years but he nonetheless made a small number of largely humanities contributions up to 1951, one year before his death at the age of 94. In contrast, Eccles retained his health and vigor until 3 years before his death and published prolifically on many subjects during his 22 years of official retirement. His last neuroscience article appeared in 1994 when he was 91. Despite poor health he continued thinking about his life-long interest, the mind-brain problem, and was attempting to complete his autobiography in the last years of his life

Intra- and interspecific polymorphisms ofLeishmania donovani andL. tropica minicircle DNA

A pair of degenerate polymerase chain reaction (PCR) primers (LEI-1, TCG GAT CC[C,T] [G,C]TG GGT AGG GGC GT; LEI-2, ACG GAT CC[G,C] [G,C][A,C]C TAT [A,T]TT ACA CC) defining a 0.15-kb segment ofLeishmania minicircle DNA was constructed. These primers amplified not only inter- but also intraspecifically polymorphic sequences. Individual sequences revealed a higher intraspecific than interspecific divergence. It is concluded that individual sequences are of limited relevance for species determination. In contrast, when a data base of 19 different sequences was analyzed in a dendrographic plot, an accurate species differentiation was feasible

Letter processing and font information during reading: beyond distinctiveness, where vision meets design

Letter identification is a critical front end of the reading process. In general, conceptualizations of the identification process have emphasized arbitrary sets of distinctive features. However, a richer view of letter processing incorporates principles from the field of type design, including an emphasis on uniformities across letters within a font. The importance of uniformities is supported by a small body of research indicating that consistency of font increases letter identification efficiency. We review design concepts and the relevant literature, with the goal of stimulating further thinking about letter processing during reading

Thomas Graham Brown (1882–1965): Behind the Scenes at the Cardiff Institute of Physiology

Thomas Graham Brown undertook seminal experiments on the neural control of locomotion between 1910 and 1915. Although elected to the Royal Society in 1927, his locomotion research was largely ignored until the 1960s when it was championed and extended by the distinguished neuroscientist, Anders Lundberg. Puzzlingly, Graham Brown's published research stopped in the 1920s and he became renowned as a mountaineer. In this article, we review his life and multifaceted career, including his active neurological service in WWI. We outline events behind the scenes during his tenure at Cardiff's Institute of Physiology in Wales, UK, including an interview with his technician, Terrence J. Surman, who worked in this institute for over half a century

Marburg Virus Infection Detected in a Common African Bat

Marburg and Ebola viruses can cause large hemorrhagic fever (HF) outbreaks with high case fatality (80–90%) in human and great apes. Identification of the natural reservoir of these viruses is one of the most important topics in this field and a fundamental key to understanding their natural history. Despite the discovery of this virus family almost 40 years ago, the search for the natural reservoir of these lethal pathogens remains an enigma despite numerous ecological studies. Here, we report the discovery of Marburg virus in a common species of fruit bat (Rousettus aegyptiacus) in Gabon as shown by finding virus-specific RNA and IgG antibody in individual bats. These Marburg virus positive bats represent the first naturally infected non-primate animals identified. Furthermore, this is the first report of Marburg virus being present in this area of Africa, thus extending the known range of the virus. These data imply that more areas are at risk for MHF outbreaks than previously realized and correspond well with a recently published report in which three species of fruit bats were demonstrated to be likely reservoirs for Ebola virus

Variation in Estimated Medicare Prescription Drug Plan Costs and Affordability for Beneficiaries Living in Different States

BACKGROUND: Medicare Part D prescription drug plans (PDPs) implemented in January 2006 are designed to improve beneficiaries’ access to pharmaceuticals and use market competition to yield affordable drug costs. Variations in estimated PDP costs for beneficiaries living in different states have not previously been characterized. OBJECTIVE: To describe variations in the estimated costs of PDPs (plan premium, copays, and coinsurance) within and across states. DESIGN: To estimate PDP costs based on 4 actual patient cases that exemplify common conditions and prescription drug combinations for Medicare beneficiaries, we used the online tool provided by the Centers for Medicare and Medicaid Services. MEASUREMENTS: Principal study outcomes included (a) variation across states in the estimated annual cost of the lowest-cost PDP for each case and (b) variation in the estimated affordability of the lowest-cost PDPs across states, based on cost-of-living-adjusted median income for zero-earner households. RESULTS: For all 4 patient cases, we found substantive within-state and between-state differences in the estimated costs of Medicare PDPs incurred by beneficiaries. The estimated annual costs to beneficiaries of the lowest-cost PDPs varied across states by as much as $320 for medications in the least expensive scenario, and by as much as$13,000 for the most expensive scenario. On average across states, a beneficiary with cost-of-living-adjusted median income would expect to spend 3%–28% of annual income to pay for medications in the lowest-cost PDPs in the 4 patient cases. The affordability of the lowest-cost plans varied across states, and for 2 of the 4 cases the lowest-cost PDP estimates were negatively correlated with cost-of-living-adjusted median income. CONCLUSIONS: Substantive differences in estimated PDP costs are evident across states for patients with common Medicare conditions. Importantly, the lowest-cost plans were not proportionally affordable with respect to state-specific cost-of-living-adjusted median income. Refinement of the Medicare drug program may be needed to improve national balance in PDP affordability for beneficiaries living in different states. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at http://dx.doi.org/10.1007/s11606-006-0018-y and is accessible for authorized users

SCAMP:standardised, concentrated, additional macronutrients, parenteral nutrition in very preterm infants: a phase IV randomised, controlled exploratory study of macronutrient intake, growth and other aspects of neonatal care

<p>Abstract</p> <p>Background</p> <p>Infants born <29 weeks gestation are at high risk of neurocognitive disability. Early postnatal growth failure, particularly head growth, is an important and potentially reversible risk factor for impaired neurodevelopmental outcome. Inadequate nutrition is a major factor in this postnatal growth failure, optimal protein and calorie (macronutrient) intakes are rarely achieved, especially in the first week. Infants <29 weeks are dependent on parenteral nutrition for the bulk of their nutrient needs for the first 2-3 weeks of life to allow gut adaptation to milk digestion. The prescription, formulation and administration of neonatal parenteral nutrition is critical to achieving optimal protein and calorie intake but has received little scientific evaluation. Current neonatal parenteral nutrition regimens often rely on individualised prescription to manage the labile, unpredictable biochemical and metabolic control characteristic of the early neonatal period. Individualised prescription frequently fails to translate into optimal macronutrient delivery. We have previously shown that a standardised, concentrated neonatal parenteral nutrition regimen can optimise macronutrient intake.</p> <p>Methods</p> <p>We propose a single centre, randomised controlled exploratory trial of two standardised, concentrated neonatal parenteral nutrition regimens comparing a standard macronutrient content (maximum protein 2.8 g/kg/day; lipid 2.8 g/kg/day, dextrose 10%) with a higher macronutrient content (maximum protein 3.8 g/kg/day; lipid 3.8 g/kg/day, dextrose 12%) over the first 28 days of life. 150 infants 24-28 completed weeks gestation and birthweight <1200 g will be recruited. The primary outcome will be head growth velocity in the first 28 days of life. Secondary outcomes will include a) auxological data between birth and 36 weeks corrected gestational age b) actual macronutrient intake in first 28 days c) biomarkers of biochemical and metabolic tolerance d) infection biomarkers and other intravascular line complications e) incidence of major complications of prematurity including mortality f) neurodevelopmental outcome at 2 years corrected gestational age</p> <p>Trial registration</p> <p>Current controlled trials: <a href="http://www.controlled-trials.com/ISRCTN76597892">ISRCTN76597892</a>; EudraCT Number: 2008-008899-14</p

Reexamining the possible benefits of visual crowding: dissociating crowding from ensemble percepts

Peripheral objects and their features become indistinct when closely surrounding but nonoverlapping objects are present. Most models suggest that this phenomenon, called crowding, reflects limitations of visual processing, but an intriguing idea is that it may be, in part, adaptive. Specifically, the mechanism generating crowding may simultaneously facilitate ensemble representations of features, leaving meaningful information about clusters of objects. In two experiments, we tested whether visual crowding and the perception of ensemble features share a common mechanism. Observers judged the orientation of a crowded bar, or the ensemble orientation of all bars in the upper and lower visual fields. While crowding was predictably stronger in the upper relative to the lower visual field, the ensemble percept did not vary between the visual fields. Featural averaging within the crowded region does not always scale with the resolution limit defined by crowding, suggesting that dissociable processes contribute to visual crowding and ensemble percepts