Cell disposition of raltegravir and newer antiretrovirals in HIV-infected patients: high inter-individual variability in raltegravir cellular penetration.

Objectives The site of pharmacological activity of raltegravir is intracellular. Our aim was to determine the extent of raltegravir cellular penetration and whether raltegravir total plasma concentration (C(tot)) predicts cellular concentration (C(cell)). Methods Open-label, prospective, pharmacokinetic study on HIV-infected patients on a stable raltegravir-containing regimen. Plasma and peripheral blood mononuclear cells were simultaneously collected during a 12 h dosing interval after drug intake. C(tot) and C(cell) of raltegravir, darunavir, etravirine, maraviroc and ritonavir were measured by liquid chromatography coupled to tandem mass spectrometry after protein precipitation. Longitudinal mixed effects analysis was applied to the C(cell)/C(tot) ratio. Results Ten HIV-infected patients were included. The geometric mean (GM) raltegravir total plasma maximum concentration (C(max)), minimum concentration (C(min)) and area under the time-concentration curve from 0-12 h (AUC(0-12)) were 1068 ng/mL, 51.1 ng/mL and 4171 ng·h/mL, respectively. GM raltegravir cellular C(max), C(min) and AUC(0-12) were 27.5 ng/mL, 2.9 ng/mL and 165 ng·h/mL, respectively. Raltegravir C(cell) corresponded to 5.3% of C(tot) measured simultaneously. Both concentrations fluctuate in parallel, with C(cell)/C(tot) ratios remaining fairly constant for each patient without a significant time-related trend over the dosing interval. The AUC(cell)/AUC(tot) GM ratios for raltegravir, darunavir and etravirine were 0.039, 0.14 and 1.55, respectively. Conclusions Raltegravir C(cell) correlated with C(tot) (r = 0.86). Raltegravir penetration into cells is low overall (∼5% of plasma levels), with distinct raltegravir cellular penetration varying by as much as 15-fold between patients. The importance of this finding in the context of development of resistance to integrase inhibitors needs to be further investigated.

Entrepreneur's Overconfidence, Private Benefits and the Market Performance of the Firm

Many firms around the world are managed and partially owned by entrepreneurs. These entrepreneurs hold under diversified portfolios and, therefore, bear idiosyncratic risk in addition to systematic risk. To compensate the additional risk borne, they extract private benefits. In this paper, we analyse how an entrepreneur's overconfidence affects the market performance of the firm, through the channel of private benefits. We show that two dimensions of overconfidence, namely overestimation of future cash-flows and underestimation of idiosyncratic risk (called miscalibration), have opposite effects on the private benefits extracted by the entrepreneur. As a consequence, firms managed and partially owned by overconfident entrepreneurs can deliver overperformance or underperformance, depending on the prevalence of overestimation or miscalibration of the beliefs of the entrepreneur.

Fresh News; The Farmers' Market Newsletter, Summer 2003

Newsletter produced by Iowa Department of Agriculture and Land Stewardship

Fresh News; The Farmers' Market Newsletter, Fall 2001

Newsletter produced by Iowa Department of Agriculture and Land Stewardship

Fresh News; The Farmers' Market Newsletter, Winter-Spring 2002

Newsletter produced by Iowa Department of Agriculture and Land Stewardship

Fresh News; The Farmers' Market Newsletter, Fall-Winter 2003

Newsletter produced by Iowa Department of Agriculture and Land Stewardship

Fresh News; The Farmers' Market Newsletter, Fall 2002

Newsletter produced by Iowa Department of Agriculture and Land Stewardship

Iowa Farmers' Market Development Manual, 2003

Farmers Market Manual produced by Iowa Departmment of Agriculture and Land Stewardship

Market Transparency, Market Quality and Sunshine Trading

This paper analyzes the implications of pre-trade transpareny on market performance. We find that transparency increases the precision held by agents, however we show that this increase in precision may not be due to prices themselves. In competitive markets, transparency increases market liquidity and reduces price volatility, whereas these results may not hold under imperfect competition. More importantly, market depth and volatility might be positively related with proper priors. Moreover, we study the incentives for liquidity traders to engage in sunshine trading. We obtain that the choice of sunshine/dark trading for a noise trader is independent of his order size, being the traders with higher liquidity needs more interested in sunshine trading, as long as this practice is desirable. Key words: Market Microstructure, Transparency, Prior Information, Market Quality, Sunshine Trading

Contagion or Interdependence in the recent Global Financial Crisis? An application to the stock markets using unconditional cross-market correlations

We consider stock market contagion as a significant increase in cross-market linkages after a shock to one country or group of countries. Under this definition we study if contagion occurred from the U.S. Financial Crisis to the rest of the major stock markets in the world by using the adjusted (unconditional) correlation coefficient approach (Forbes and Rigobon, 2002) which consists of testing if average crossmarket correlations increase significantly during the relevant period of turmoil. We would not reject the null hypothesis of interdependence in favour of contagion if the increase in correlation only suggests a continuation of high linkages in all state of the world. Moreover, if contagion occurs, this would justify the intervention of the IMF and the suddenly portfolio restructuring during the period under study.

Market rewards to patterns on increasing earnings: do cash flow patterns, accruals manipulation and real activities manipulation matter?

This study explores whether firms have differential price-earnings multiples associated with their means of achieving a sequential pattern of increasing positive earnings. Our main findings show that market participants assign higher price-earnings multiples to firms when their pattern of increasing earnings is supported by the same pattern of increasing cash flows. Market participants assign lower price-earnings multiples to firms suspect of having engaged in accrual-based earnings management, sales manipulation, and overproduction to achieve the earnings pattern. We find, however, that market participants do not penalize firms suspect of having achieved the earnings pattern through the opportunistic reduction of discretionary expenses.

Effective Structural Concrete Repair, Volume 2 of 3, Use of FRP to Prevent Chloride Penetration in Bridge Columns, March 2004

Structural concrete is one of the most commonly used construction materials in the United States. However, due to changes in design specifications, aging, vehicle impact, etc. – there is a need for new procedures for repairing concrete (reinforced or pretressed) superstructures and substructures. Thus, the overall objective of this investigation was to develop innovative cost effective repair methods for various concrete elements. In consultation with the project advisory committee, it was decided to evaluate the following three repair methods: • Carbon fiber reinforced polymers (CFRPs) for use in repairing damaged prestressed concrete bridges • Fiber reinforced polymers (FRPs) for preventing chloride penetration of bridge columns • Various patch materials The initial results of these evaluations are presented in this three volume final report. Each evaluation is briefly described in the following paragraphs. A more detailed abstract of each evaluation accompanies the volume on that particular investigation.

Sediment penetration depths of epi- and infaunal ostracods from Lake Geneva (Switzerland)

Many (palaeo-)environmental parameters can be deduced from ecological and chemical analyses of ostracods. However, the specific ecology of each taxon has a great impact on its reaction to changing environmental conditions. As a consequence, each taxon records these changes differently. The mean penetration depth (MPD) and relative individual abundances have been documented along sediment depth profiles for the dominant sub-littoral to profundal species of ostracods in western Lake Geneva, Switzerland, and this data can be used to estimate their preferential habitat in terms of sediment depths. Isocypris beauchampi, Limnocytherina sanctipatricii, Cypria ophtalmica forma lacustris at 13-m water depths, Limnocythere inopinata, and a winter generation of Herpetocypris reptans have the shallowest habitat preferences at the study sites (MPDs of 0.45, 0.48, 0.49, 0.60, and 0.81 cm, respectively). These results suggest that these populations may be regarded as being preferentially epifaunal forms. Populations of Cytherissa lacustris (MPDs of 0.61, 0.73, and 0.82 cm at 13-, 33-, and 70-m water depths, respectively), Cypria ophtalmica forma lacustris at 70 m (MPD = 0.96 cm), Fabaeformiscandona caudata (MPD = 0.99 cm), and a summer generation of Herpetocypris reptans (MPD = 1.03 cm) were identified as being infaunal. Candona neglecta is the species that was found the deepest in the sediment of Lake Geneva, with MPDs of 0.65, 1.22, and 1.30 cm at 13-, 33-, and 70-m water depths, respectively. Information on the sediment texture and oxygen concentrations inferred from the analyses of sediment pore water suggest that the oxygen content of the sediment pore water is not the only dominant parameter controlling the differences in ostracod sediment penetration depths observed among the different sites, but that they might also be influenced by the sediment 'softness,' which itself depends on grain size, water content, and the abundance of organic matter in sediment.

Annual Review of the European Football Players' Labour Market / Etude annuelle du marché du travail européen des footballeurs

The key reference on the labour market and the logics of squad formation in the big-5 European leagues. One hundred richly coloured pages, illustrated by graphics, maps, rankings, statistical models and analysis in French and English which inform managers about potential strategies to put their clubs on the road to success help managers of federations and players' unions to understand current trends and to take decisions ... suggest to journalists new lines of investigation likely to interest the general public allow researchers and students to benefit from reliable and comparable sources, developed with the greatest possible rigour ... give fans the possibility to understand in detail the dynamics at work in their favourite sport and club.

Inspection Intensity and Market Structure, October 2005

An investigation of financing an inspection policy while allowing the enforcement of a market regulation is described. A simple model shows that the intensity of controls depends on the market structure. Under a given number of firms, the per-firm probability of controls is lower than one, since firms’ incentive to comply with regulation holds under positive profits. In this case, a lump-sum tax is used for limiting distortions coming from financing with a fixed fee. Under free entry, the per-firm probability of controls is equal to one, and only a fixed fee that prevents excess entry is used to finance inspection.