Toward Less Monopoly

Acceptance of the importance of economics in antitrust law has become widespread. The Association of American Law Schools has sponsored economic studies to supplement legal teaching materials; practicing lawyers increasingly are seeking economic aid in preparing for antitrust litigation; and recently a federal judge has obtained the assistance of a trained economist for a major Sherman Act case. In addition economics has an equally important role in determining what the law should be

The Prerequisites and Effects of Resale Price Maintenance

Present law permits the makers of most identifiable products to fix the prices at which these products may be resold (or below which they may not be resold) in most states in the United States. This is permissible on goods which are in free and open competition with other goods of the same general class, and no agreements among competing sellers at any level are sanctioned. These safeguards to competition provide the basis for the contention that the fair-trade laws do not eliminate competition or raise prices. The opposing view is that competition is as important in distribution as in manufacturing, and that dealer competition is inevitably eliminated. Consumers are thus limited in the range of choices they may exercise with respect to service facilities, convenience, or price in the sale of price-maintenance products

Population-Wide Emergence of Antiviral Resistance during Pandemic Influenza

Background: The emergence of neuraminidase inhibitor resistance has raised concerns about the prudent use of antiviral drugs in response to the next influenza pandemic. While resistant strains may initially emerge with compromised viral fitness, mutations that largely compensate for this impaired fitness can arise. Understanding the extent to which these mutations affect the spread of disease in the population can have important implications for developing pandemic plans. Methodology/Principal Findings: By employing a deterministic mathematical model, we investigate possible scenarios for the emergence of population-wide resistance in the presence of antiviral drugs. The results show that if the treatment level (the fraction of clinical infections which receives treatment) is maintained constant during the course of the outbreak, there is an optimal level that minimizes the final size of the pandemic. However, aggressive treatment above the optimal level can substantially promote the spread of highly transmissible resistant mutants and increase the total number of infections. We demonstrate that resistant outbreaks can occur more readily when the spread of disease is further delayed by applying other curtailing measures, even if treatment levels are kept modest. However, by changing treatment levels over the course of the pandemic, it is possible to reduce the final size of the pandemic below the minimum achieved at the optimal constant level. This reduction can occur with low treatment levels during the early stages of the pandemic, followed by a sharp increase in drug-use before the virus becomes widely spread. Conclusions/Significance: Our findings suggest that an adaptive antiviral strategy with conservative initial treatment levels, followed by a timely increase in the scale of drug-use, can minimize the final size of a pandemic while preventing large outbreaks of resistant infections

Anthromes dispaying evidence of weekly cycles in active fire data cover 70% of the global land surface

Across the globe, human activities have been gaining importance relatively to climate and ecology as the main controls on fire regimes and consequently human activity became an important driver of the frequency, extent and intensity of vegetation burning worldwide. Our objective in the present study is to look for weekly cycles in vegetation fire activity at global scale as evidence of human agency, relying on the original MODIS active fire detections at 1 km spatial resolution (MCD14ML) and using novel statistical methodologies to detect significant periodicities in time series data. We tested the hypotheses that global fire activity displays weekly cycles and that the weekday with the fewest fires is Sunday. We also assessed the effect of land use and land cover on weekly fire cycle significance by testing those hypotheses separately for the Villages, Settlements, Croplands, Rangelands, Seminatural, and Wildlands anthromes. Based on a preliminary data analysis of the daily global active fire counts periodogram, we developed an harmonic regression model for the mean function of daily fire activity and assumed a linear model for the de-seasonalized time series. For inference purposes, we used a Bayesian methodology and constructed a simultaneous 95% credible band for the mean function. The hypothesis of a Sunday weekly minimum was directly investigated by computing the probabilities that the mean functions of every weekday (Monday to Saturday) are inside the credible band corresponding to mean Sunday fire activity. Since these probabilities are small, there is statistical evidence of significantly fewer fires on Sunday than on the other days of the week. Cropland, rangeland, and seminatural anthromes, which cover 70% of the global land area and account for 94% of the active fires analysed, display weekly cycles in fire activity. Due to lower land management intensity and less strict control over fire size and duration, weekly cycles in Rangelands and Seminatural anthromes, which jointly account for 53.46% of all fires, although statistically significant are weaker than those detected in Croplandsinfo:eu-repo/semantics/publishedVersio

Post-exposure prophylaxis during pandemic outbreaks

<p>Abstract</p> <p>Background</p> <p>With the rise of the second pandemic wave of the novel influenza A (H1N1) virus in the current season in the Northern Hemisphere, pandemic plans are being carefully re-evaluated, particularly for the strategic use of antiviral drugs. The recent emergence of oseltamivir-resistant in treated H1N1 patients has raised concerns about the prudent use of neuraminidase inhibitors for both treatment of ill individuals and post-exposure prophylaxis of close contacts.</p> <p>Methods</p> <p>We extended an established population dynamical model of pandemic influenza with treatment to include post-exposure prophylaxis of close contacts. Using parameter estimates published in the literature, we simulated the model to evaluate the combined effect of treatment and prophylaxis in minimizing morbidity and mortality of pandemic infections in the context of transmissible drug resistance.</p> <p>Results</p> <p>We demonstrated that, when transmissible resistant strains are present, post-exposure prophylaxis can promote the spread of resistance, especially when combined with aggressive treatment. For a given treatment level, there is an optimal coverage of prophylaxis that minimizes the total number of infections (final size) and this coverage decreases as a higher proportion of infected individuals are treated. We found that, when treatment is maintained at intermediate levels, limited post-exposure prophylaxis provides an optimal strategy for reducing the final size of the pandemic while minimizing the total number of deaths. We tested our results by performing a sensitivity analysis over a range of key model parameters and observed that the incidence of infection depends strongly on the transmission fitness of resistant strains.</p> <p>Conclusion</p> <p>Our findings suggest that, in the presence of transmissible drug resistance, strategies that prioritize the treatment of only ill individuals, rather than the prophylaxis of those suspected of being exposed, are most effective in reducing the morbidity and mortality of the pandemic. The impact of post-exposure prophylaxis depends critically on the treatment level and the transmissibility of resistant strains and, therefore, enhanced surveillance and clinical monitoring for resistant mutants constitutes a key component of any comprehensive plan for antiviral drug use during an influenza pandemic.</p

15-PGJ2, but not thiazolidinediones, inhibits cell growth, induces apoptosis, and causes downregulation of Stat3 in human oral SCCa cells

Activation of peroxisome proliferator-activated receptor gamma (PPARγ) has been linked to induction of differentiation, cell growth inhibition and apoptosis in several types of human cancer. However, the possible effects of PPARγ agonists on human oral squamous cell carcinoma have not yet been reported. In this study, treatment with 15-deoxy-Δ12,14-PGJ2 (15-PGJ2), a natural PPARγ ligand, induced a significant reduction of oral squamous cell carcinoma cell growth, which was mainly attributed to upregulation of apoptosis. Interestingly, rosiglitazone and ciglitazone, two members of the thiazolidinedione family of PPARγ activators, did not exert a growth inhibitory effect. Given the critical role that the oncogene signal transducer and activator of transcription 3 (Stat3) plays in head and neck carcinogenesis, its potential regulation by PPARγ ligands was also examined. Treatment of oral squamous cell carcinoma cells with 15-PGJ2 induced an initial reduction and eventual elimination of both phosphorylated and unphosphorylated Stat3 protein levels. In contrast, other PPARγ did not induce similar effects. Our results provide the first evidence of significant antineoplastic effects of 15-PGJ2 on human oral squamous cell carcinoma cells, which may be related to downmodulation of Stat3 and are at least partly mediated through PPARγ-independent events

Bafilomycin A1 activates respiration of neuronal cells via uncoupling associated with flickering depolarization of mitochondria

Bafilomycin A1 (Baf) induces an elevation of cytosolic Ca2+ and acidification in neuronal cells via inhibition of the V-ATPase. Also, Baf uncouples mitochondria in differentiated PC12 (dPC12), dSH-SY5Y cells and cerebellar granule neurons, and markedly elevates their respiration. This respiratory response in dPC12 is accompanied by morphological changes in the mitochondria and decreases the mitochondrial pH, Ca2+ and ΔΨm. The response to Baf is regulated by cytosolic Ca2+ fluxes from the endoplasmic reticulum. Inhibition of permeability transition pore opening increases the depolarizing effect of Baf on the ΔΨm. Baf induces stochastic flickering of the ΔΨm with a period of 20 ± 10 s. Under conditions of suppressed ATP production by glycolysis, oxidative phosphorylation impaired by Baf does not provide cells with sufficient ATP levels. Cells treated with Baf become more susceptible to excitation with KCl. Such mitochondrial uncoupling may play a role in a number of (patho)physiological conditions induced by Baf

Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.

BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112