The B-vitamins comprise a group of eight water soluble vitamins that perform essential, closely inter-related roles in cellular functioning, acting as co-enzymes in a vast array of catabolic and ...anabolic enzymatic reactions. Their collective effects are particularly prevalent to numerous aspects of brain function, including energy production, DNA/RNA synthesis/repair, genomic and non-genomic methylation, and the synthesis of numerous neurochemicals and signaling molecules. However, human epidemiological and controlled trial investigations, and the resultant scientific commentary, have focused almost exclusively on the small sub-set of vitamins (B9/B12/B6) that are the most prominent (but not the exclusive) B-vitamins involved in homocysteine metabolism. Scant regard has been paid to the other B vitamins. This review describes the closely inter-related functions of the eight B-vitamins and marshals evidence suggesting that adequate levels of all members of this group of micronutrients are essential for optimal physiological and neurological functioning. Furthermore, evidence from human research clearly shows both that a significant proportion of the populations of developed countries suffer from deficiencies or insufficiencies in one or more of this group of vitamins, and that, in the absence of an optimal diet, administration of the entire B-vitamin group, rather than a small sub-set, at doses greatly in excess of the current governmental recommendations, would be a rational approach for preserving brain health.
A World of Struggle Kennedy, David
2018, 2016., 20180424, 2016, 2018-04-24
eBook
A World of Strugglereveals the role of expert knowledge in our political and economic life. As politicians, citizens, and experts engage one another on a technocratic terrain of irresolvable argument ...and uncertain knowledge, a world of astonishing inequality and injustice is born.
In this provocative book, David Kennedy draws on his experience working with international lawyers, human rights advocates, policy professionals, economic development specialists, military lawyers, and humanitarian strategists to provide a unique insider's perspective on the complexities of global governance. He describes the conflicts, unexamined assumptions, and assertions of power and entitlement that lie at the center of expert rule. Kennedy explores the history of intellectual innovation by which experts developed a sophisticated legal vocabulary for global management strangely detached from its distributive consequences. At the center of expert rule is struggle: myriad everyday disputes in which expertise drifts free of its moorings in analytic rigor and observable fact. He proposes tools to model and contest expert work and concludes with an in-depth examination of modern law in warfare as an example of sophisticated expertise in action.
Charting a major new direction in global governance at a moment when the international order is ready for change, this critically important book explains how we can harness expert knowledge to remake an unjust world.
The dark sides of virtue Kennedy, David
2008., 20110627, 2011, 2004, 2004-01-01, 20050101, 20040101
eBook
In this provocative and timely book, David Kennedy explores what can go awry when we put our humanitarian yearnings into action on a global scale--and what we can do in response.
Could some vaccines drive the evolution of more virulent pathogens? Conventional wisdom is that natural selection will remove highly lethal pathogens if host death greatly reduces transmission. ...Vaccines that keep hosts alive but still allow transmission could thus allow very virulent strains to circulate in a population. Here we show experimentally that immunization of chickens against Marek's disease virus enhances the fitness of more virulent strains, making it possible for hyperpathogenic strains to transmit. Immunity elicited by direct vaccination or by maternal vaccination prolongs host survival but does not prevent infection, viral replication or transmission, thus extending the infectious periods of strains otherwise too lethal to persist. Our data show that anti-disease vaccines that do not prevent transmission can create conditions that promote the emergence of pathogen strains that cause more severe disease in unvaccinated hosts.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Although less common than the evolution of antimicrobial drug resistance, vaccine resistance can and has evolved. How likely is it that COVID-19 vaccines currently in development will be undermined ...by viral evolution? We argue that this can be determined by repurposing samples that are already being collected as part of clinical trials. Such information would be useful for prioritizing investment among candidate vaccines and maximizing the potential long-term impact of COVID-19 vaccines.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Subjective alertness and optimal cognitive function, including in terms of attention, spatial/working memory and executive function, are intrinsic to peak performance in many sports. Consumption of a ...number of plant-derived ‘secondary metabolite’ phytochemicals can modulate these psychological parameters, although there is a paucity of evidence collected in a sporting context. The structural groups into which these phytochemicals fall—phenolics, terpenes and alkaloids—vary in terms of the ecological roles they play for the plant, their toxicity and the extent to which they exert direct effects on brain function. The phenolics, including polyphenols, play protective roles in the plant, and represent a natural, benign component of the human diet. Increased consumption has been shown to improve cardiovascular function and is associated with long-term brain health. However, whilst short-term supplementation with polyphenols has been shown to consistently modulate cerebral blood-flow parameters, evidence of direct effects on cognitive function and alertness/arousal is currently comparatively weak. Terpenes play both attractant and deterrent roles in the plant, and typically occur less frequently in the diet. Single doses of volatile monoterpenes derived from edible herbs such as sage (
Salvia officinalis/lavandulaefolia
) and peppermint (
Mentha piperita
), diterpene-rich
Ginkgo biloba
extracts and triterpene-containing extracts from plants such as ginseng (
Panax ginseng/quinquefolius
) and
Bacopa monnieri
have all been shown to enhance relevant aspects of cognitive function and alertness. The alkaloids play toxic defensive roles in the plant, including via interference with herbivore brain function. Whilst most alkaloids are inappropriate in a sporting context due to toxicity and legal status, evidence suggests that single doses of nicotine and caffeine may be able to enhance relevant aspects of cognitive function and/or alertness. However, their benefits may be confounded by habituation and withdrawal effects in the longer term. The efficacy of volatile terpenes, triterpene-rich extracts and products combining low doses of caffeine with other phytochemicals deserves more research attention.
Of war and law Kennedy, David; Kennedy, David
2006., 20090110, 2009, 2006, 2006-01-01
eBook
Modern war is law pursued by other means. Once a bit player in military conflict, law now shapes the institutional, logistical, and physical landscape of war. At the same time, law has become a ...political and ethical vocabulary for marking legitimate power and justifiable death. As a result, the battlespace is as legally regulated as the rest of modern life. In Of War and Law, David Kennedy examines this important development, retelling the history of modern war and statecraft as a tale of the changing role of law and the dramatic growth of law's power. Not only a restraint and an ethical yardstick, law can also be a weapon--a strategic partner, a force multiplier, and an excuse for terrifying violence. Kennedy focuses on what can go wrong when humanitarian and military planners speak the same legal language--wrong for humanitarianism, and wrong for warfare. He argues that law has beaten ploughshares into swords while encouraging the bureaucratization of strategy and leadership. A culture of rules has eroded the experience of personal decision-making and responsibility among soldiers and statesmen alike. Kennedy urges those inside and outside the military who wish to reduce the ferocity of battle to understand the new roles--and the limits--of law. Only then will we be able to revitalize our responsibility for war.
A common assumption in the evolution of virulence theory literature is that pathogens transmit better when they exploit their host more heavily, but by doing so, they impose a greater risk of killing ...their host, thus truncating infectious periods and reducing their own opportunities for transmission. Here, I derive an equation for the magnitude of this cost in terms of the infection fatality rate, and in doing so, I show that there are many cases where mortality costs are too small to plausibly constrain increases in host exploitation by pathogens. I propose that pathogen evolution may often be constrained by detection costs, whereby hosts alter their behaviour when infection is detectable, and thus reduce pathogen opportunities for onward transmission. I then derive an inequality to illustrate when mortality costs or detection costs impose stronger constraints on pathogen evolution, and I use empirical data from the literature to demonstrate that detection costs are frequently large in both human and animal populations. Finally, I give examples of how evolutionary predictions can change depending on whether costs of host exploitation are borne out through mortality or detection.
Automatic segmentation of subcortical structures in human brain MR images is an important but difficult task due to poor and variable intensity contrast. Clear, well-defined intensity features are ...absent in many places along typical structure boundaries and so extra information is required to achieve successful segmentation. A method is proposed here that uses manually labelled image data to provide anatomical training information. It utilises the principles of the Active Shape and Appearance Models but places them within a Bayesian framework, allowing probabilistic relationships between shape and intensity to be fully exploited. The model is trained for 15 different subcortical structures using 336 manually-labelled T1-weighted MR images. Using the Bayesian approach, conditional probabilities can be calculated easily and efficiently, avoiding technical problems of ill-conditioned covariance matrices, even with weak priors, and eliminating the need for fitting extra empirical scaling parameters, as is required in standard Active Appearance Models. Furthermore, differences in boundary vertex locations provide a direct, purely local measure of geometric change in structure between groups that, unlike voxel-based morphometry, is not dependent on tissue classification methods or arbitrary smoothing. In this paper the fully-automated segmentation method is presented and assessed both quantitatively, using Leave-One-Out testing on the 336 training images, and qualitatively, using an independent clinical dataset involving Alzheimer's disease. Median Dice overlaps between 0.7 and 0.9 are obtained with this method, which is comparable or better than other automated methods. An implementation of this method, called FIRST, is currently distributed with the freely-available FSL package.
► Automated segmentation of 15 subcortical structures with full Bayesian formulation. ► Vertex-analysis for detecting local geometric changes with no arbitrary smoothing. ► Good performance over a wide range of demographics and T1-weighted images. ► Avoids arbitrary scaling parameters and ill-conditioning in usual appearance models. ► Freely available as part of FSL — tool is called FIRST.
Vaccines and antimicrobial drugs both impose strong selection for resistance. Yet only drug resistance is a major challenge for 21st century medicine. Why is drug resistance ubiquitous and not ...vaccine resistance? Part of the answer is that vaccine resistance is far less likely to evolve than drug resistance. But what happens when vaccine resistance does evolve? We review six putative cases. We find that in contrast to drug resistance, vaccine resistance is harder to detect and harder to confirm and that the mechanistic basis is less well understood. Nevertheless, in the cases we examined, the pronounced health benefits associated with vaccination have largely been sustained. Thus, we contend that vaccine resistance is less of a concern than drug resistance because it is less likely to evolve and when it does, it is less harmful to human and animal health and well-being. Studies of pathogen strains that evolve the capacity to replicate and transmit from vaccinated hosts will enhance our ability to develop next-generation vaccines that minimize the risk of harmful pathogen evolution.
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