Beyond antioxidants: the cellular and molecular interactions of flavonoids and how these underpin their actions on the brain

The consumption of flavonoid-rich foods and beverages has been suggested to limit the neurodegeneration associated with a variety of neurological disorders and to prevent or reverse normal or abnormal deteriorations in cognitive performance. Flavonoids mediate these effects via a number of routes, including a potential to protect neurons against injury induced by neurotoxins, an ability to suppress neuroinflammation and a potential to promote memory, learning and cognitive function. Originally, it was thought that such actions were mediated by the antioxidant capacity of flavonoids. However, their limited absorption and their low bioavailability in the brain suggest that this explanation is unlikely. Instead, this multiplicity of effects appears to be underpinned by three separate processes: first, through their interactions with important neuronal and glial signalling cascades in the brain, most notably the phosphatidylinositol 3-kinase/Akt and mitogen-activated protein kinase pathways that regulate pro-survival transcription factors and gene expression; second, through an ability to improve peripheral and cerebral blood flow and to trigger angiogenesis and neurogenesis in the hippocampus; third, by their capacity to directly react with and scavenge neurotoxic species and pro-inflammatory agents produced in the brain as a result of both normal and abnormal brain ageing. The present review explores the potential inhibitory or stimulatory actions of flavonoids within these three systems and describes how such interactions are likely to underlie neurological effects

Rotator cuff tears: is non-surgical management effective?

This is an Accepted Manuscript of an article published by Taylor & Francis in Physical therapy Reviews on 28 December 2016, available online at: https://doi.org/10.1080/10833196.2016.1271504.Background: Rotator cuff-related shoulder pain is a common musculoskeletal complaint with an increasing number of people with shoulder pain undergoing surgical repair each year. The relationship between rotator cuff tendon tears and shoulder pain remains equivocal due to the high prevalence of tears in people without symptoms, which suggests that a proportion of people will undergo surgery on tissues not related to their symptoms. As a result there have been suggestions to initially manage atraumatic tears non-surgically. Objectives: The objective of this narrative review was to present current evidence regarding the assessment and management of full-thickness rotator cuff tears. Major findings: To date, three randomised controlled trials have compared surgical with non-surgical management of rotator cuff tears. Outcomes show a small but non-significant effect in favour of surgery. Only one study has looked at long-term outcomes of greater than one year. Overall 129 subjects have completed a course of non-surgical management and therefore low participant numbers may not be sufficient to draw firm conclusions. Conclusions: Current evidence currently supports the consideration of a non-surgical approach in the management of people with shoulder symptoms and identified rotator cuff tears, for a period of time.Peer reviewedFinal Accepted Versio

Why Do Sellers (Usually) Prefer Auctions?

We compare the most common methods for selling a company or other asset when participation is costly: a simple simultaneous auction, and a sequential process in which potential buyers decide in turn whether or not to enter the bidding. The sequential process is always more efficient. But pre-emptive bids transfer surplus from the seller to buyers. Because the auction is more conducive to entry - precisely because of its inefficiency - it usually generates higher expected revenue. We also discuss the effects of lock-ups, matching rights, break-up fees (as in takeover battles), entry subsidies, etc.Auctions, jump bidding, sequential sales, procurement, entry

Auctions vs. Negotiations

Which is the more profitable way to sell a company: a public auction or an optimally structured negotiation with a smaller number of bidders? We show that under standard assumptions the public auction is always preferable, even if it forfeits all the seller's negotiating power, including the ability to withdraw the object from sale, provided that it attracts at least one extra bidder. An immediate public auction also dominates negotiating while maintaining the right to hold an auction subsequently with more bidders. The results hold for both the standard independent private values model and a common values model. They suggest that the value of negotiating skill is small relative to the value of additional competition.

The Tobacco Deal

[Forthcoming in Brookings Papers on Economic Activity] We analyse the major economic issues raised by the 1997 Tobacco Resolution and the ensuing proposed legislation that were intended to settle tobacco litigation in the United States. By settling litigation largely in return for tax increases, the Resolution was a superb example of a "win- win" deal. The taxes would cost the companies about $1 billion per year, but yield the government about$13 billion per year, and allow the lawyers to claim fees based on hundreds of billions in “damages”. Only consumers, in whose name many of the lawsuits were filed, lost out. Though the strategy seems brilliant for the parties involved, the execution was less intelligent. We show that alternative taxes would be considerably superior to those proposed, and explain problems with the damage payments required from the firms, and the legal protections offered to them. We argue that the legislation was not particularly focused on youth smoking, despite the rhetoric. However, contrary to conventional wisdom, youth smokers are not especially valuable to the companies, so marketing restrictions are a sensible part of any deal. The individual state settlements set very dangerous examples which could open up unprecedented opportunities for collusion throughout the economy, and the multistate settlement of November 1998 is equally flawed. The fees proposed for the lawyers (around $15 billion) and the equally remarkable proposed payoff for Liggett (perhaps$400 million annually, for a company with a prior market value of about $100 million) also set terrible examples. We conclude with some views about how public policy might do better.

Price Controls and Consumer Surplus

The condition for when a price control increases consumer welfare in perfect competition is tighter than often realised. When demand is linear, a small restriction on price only increases consumer surplus if the elasticity of demand exceeds the elasticity of supply; with log-linear or constant-elasticity, demand consumers are always hurt by price controls. The results are best understood - and can be related to monopoly-theory results - using the fact that consumer surplus equals the area between the demand curve and the industry marginal-revenue curve.Rationing, Allocative Efficiency, Microeconomic Theory, Marginal Revenue, Minimum Wage, Rent Control, Consumer Welfare

When are Auctions Best?

We compare the two most common bidding processes for selling a company or other asset when participation is costly to buyers. In an auction all entry decisions are made prior to any bidding. In a sequential bidding process earlier entrants can make bids before later entrants choose whether to compete. The sequential process is more efficient because entrants base their decisions on superior information. But pre-emptive bids transfer surplus from the seller to buyers. Because the auction is more conducive to entry in several ways it usually generates higher expected revenue.auctions, jump bidding, sequential sales, procurement, entry.