The Influence of Special Interest Groups on Copyright Law and Policy—A Comparison of the Legislative Processes in the United States and Switzerland

In April 2016, the Office of the United States Trade Representative placed Switzerland on the Watch List of its 2016 Special 301 Report, which contains an annual review of the state of intellectual property rights protection and enforcement in U.S. trading partners around the world. According to the Report, the decision to put Switzerland on the Watch List was premised on U.S. concerns regarding specific difficulties in Switzerland’s system of online copyright protection and enforcement, particularly the “Logistep” ruling issued by the Federal Supreme Court of Switzerland in 2010. Although the Swiss authorities have acknowledged the difficulties mentioned in the Special 301 Report, the fierce criticism raised by the U.S. seems inappropriate, as the Swiss federal legislature decided long ago to remedy the shortcomings in the Swiss Copyright Act and initiated the appropriate legislative procedures in 2012. Due to the nature of Switzerland’s direct democracy, however, the legislative process is still in progress, with the parliament awaiting the results of the public consultation procedure during the course of the year. Despite this clear roadmap, the United States is increasing its pressure on the Swiss government and encourages it to move forward with concrete and effective measures that address copyright piracy in an appropriate and effective manner. Over the same period of time, the most recent legislative proposals in the field of copyright law in the United States have come to an abrupt halt. Unprecedented public outcry against the legislative proposals in 2012 led to the so-called SOPA and PIPA online protests, which resulted in a political deadlock in the field of copyright law and policymaking. In the eyes of several legal scholars, these protests have revealed a lack of democratic legitimacy in the federal legislative process in the United States, as it denies the general public any meaningful form of participation. Focusing on the respective histories of copyright law and policy in the United States and Switzerland, this Article examines how copyright lobbyists and other special interest groups assert their influence in the legislative process, and how their influence can be diminished. Illustrated by the example of copyright legislation, the Article shows that the instruments of direct democracy in Switzerland—which ultimately caused the delays addressed in the Special 301 Report—not only effectively counterbalance the effect of legislative lobbying, but also help to enhance public acceptance of legislative proposals in general. Ultimately, this Article claims that the United States could strengthen the democratic legitimacy of its federal legislative process by implementing a mandatory public consultation procedure based on the model of Switzerland, which might create a first step towards breaking the current standoff in U.S. copyright lawmaking

Radar-based assessment of hail frequency in Europe

In this study we present a unique 10 year climatology of severe convective storm tracks for a large European area covering Germany, France, Belgium and Luxembourg. For the period 2005–2014, a high-resolution hail potential composite of 1×1 km$^{2}$ is produced from two-dimensional radar reflectivity and lightning data. Individual hailstorm tracks as well as their physical properties, such as radar reflectivity along the tracks, were reconstructed for the entire time period using the Convective Cell Tracking Algorithm (CCTA2D). A sea-to-continent gradient in the number of hail days per year is found to be present over the whole domain. In addition, the highest number of severe storms is found on the leeward side of low mountain ranges such as the Massif Central in France and the Swabian Jura in southwest Germany. A latitude shift in the hail peak month is observed between the northern part of Germany, where hail occurs most frequently in August, and southern France, where the maximum amount of hail is 2 months earlier. The longest footprints with high reflectivity values occurred on 9 June 2014 and on 28 July 2013 with lengths reaching up to 500 km. Both events were associated with hailstones measuring up to 10 cm diameter, which caused damage in excess of EUR 2 billion

Effects of graded levels of dietary pomegranate peel on methane and nitrogen losses, and metabolic and health indicators in dairy cows

This study aimed to quantify the effects of dietary inclusion of tannin-rich pomegranate peel (PP) on intake, methane and nitrogen (N) losses, and metabolic and health indicators in dairy cows. Four multiparous, late-lactating Brown Swiss dairy cows (796 kg body weight; 29 kg/d of energy corrected milk yield) were randomly allocated to 3 treatments in a randomized cyclic change-over design with 3 periods, each comprising 14 d of adaptation, 7 d of milk, urine, and feces collection, and 2 d of methane measurements. Treatments were formulated using PP that replaced on a dry matter (DM) basis 0% (control), 5%, and 10% of the basal mixed ration (BMR) consisting of corn and grass silage, alfalfa, and concentrate. Gaseous exchange of the cows was determined in open-circuit respiration chambers. Blood samples were collected on d 15 of each period. Individual feed intake as well as feces and urine excretion were quantified, and representative samples were collected for analyses of nutrients and phenol composition. Milk was analyzed for concentrations of fat, protein, lactose, milk urea N, and fatty acids. Total phenols and antioxidant capacity in milk and plasma were determined. In serum, the concentrations of urea and bilirubin as well as the activities of alanine aminotransferase (ALT), aspartate aminotransferase, glutamate dehydrogenase, alkaline phosphatase, and γ-glutamyl transferase were measured. The data was subjected to ANOVA with the Mixed procedure of SAS, with treatment and period as fixed and animal as random effects. The PP and BMR contained 218 and 3.5 g total extractable tannins per kg DM, respectively, and thereof 203 and 3.3 g hydrolyzable tannins. Total DM intake, energy corrected milk, and methane emission (total, yield, and intensity) were not affected by PP supplementation. The proportions of C18:2 n-6 and C18:3 n-3 in milk increased linearly as the amount of PP increased in the diet. Milk urea N, blood urea N, and urinary N excretion decreased linearly with the increase in dietary PP content. Total phenols and antioxidant capacity in milk and plasma were not affected by the inclusion of PP. The activity of ALT increased in a linear manner with the inclusion of PP. In conclusion, replacing up to 10% of BMR with PP improved milk fatty acid composition and alleviated metabolic and environmental N load. However, the elevated serum ALT activity indicates an onset of liver stress even at 5% PP, requiring the development of adaptation protocols for safe inclusion of PP in ruminant diets

High-dose Cefepime vs Carbapenems for Bacteremia Caused by Enterobacterales With Moderate to High Risk of Clinically Significant AmpC β-lactamase Production

BACKGROUND: Limited data suggest that serious infections caused by Enterobacterales with a moderate to high risk of clinically significant AmpC production can be successfully treated with cefepime if the cefepime minimum inhibitory concentration (MIC) is ≤2 µg/mL. However, isolates with a cefepime-susceptible dose-dependent (SDD) MIC of 4-8 µg/mL should receive a carbapenem due to target attainment and extended-spectrum β-lactamase (ESBL) concerns. METHODS: This was a retrospective cohort study of hospitalized patients with RESULTS: Of the 315 patients included, 169 received cefepime and 146 received a carbapenem (ertapenem n = 90, meropenem n = 56). Cefepime was not associated with an increased risk of 30-day mortality compared with carbapenem therapy (adjusted hazard ratio [aHR], 1.45; 95% CI, 0.79-2.14), which was consistent for patients with cefepime SDD isolates (aHR, 1.19; 95% CI, 0.52-1.77). Multivariable weighted Cox models identified Pitt bacteremia score \u3e4 (aHR, 1.41; 95% CI, 1.04-1.92), deep infection (aHR, 2.27; 95% CI, 1.21-4.32), and ceftriaxone-resistant AmpC-E (aHR, 1.32; 95% CI, 1.03-1.59) to be independent predictors associated with increased mortality risk, while receipt of prolonged-infusion β-lactam was protective (aHR, 0.67; 95% CI, 0.40-0.89). CONCLUSIONS: Among patients with bacteremia caused by Enterobacterales with moderate to high risk of clinically significant AmpC production, these data demonstrate similar risk of 30-day mortality for high-dose cefepime or a carbapenem as definitive β-lactam therapy

O-mannosyl phosphorylation of alpha-dystroglycan is required for laminin binding.

Alpha-dystroglycan (alpha-DG) is a cell-surface glycoprotein that acts as a receptor for both extracellular matrix proteins containing laminin-G domains and certain arenaviruses. Receptor binding is thought to be mediated by a posttranslational modification, and defective binding with laminin underlies a subclass of congenital muscular dystrophy. Using mass spectrometry- and nuclear magnetic resonance (NMR)-based structural analyses, we identified a phosphorylated O-mannosyl glycan on the mucin-like domain of recombinant alpha-DG, which was required for laminin binding. We demonstrated that patients with muscle-eye-brain disease and Fukuyama congenital muscular dystrophy, as well as mice with myodystrophy, commonly have defects in a postphosphoryl modification of this phosphorylated O-linked mannose, and that this modification is mediated by the like-acetylglucosaminyltransferase (LARGE) protein. These findings expand our understanding of the mechanisms that underlie congenital muscular dystrophy

On Bernoulli Decompositions for Random Variables, Concentration Bounds, and Spectral Localization

As was noted already by A. N. Kolmogorov, any random variable has a Bernoulli component. This observation provides a tool for the extension of results which are known for Bernoulli random variables to arbitrary distributions. Two applications are provided here: i. an anti-concentration bound for a class of functions of independent random variables, where probabilistic bounds are extracted from combinatorial results, and ii. a proof, based on the Bernoulli case, of spectral localization for random Schroedinger operators with arbitrary probability distributions for the single site coupling constants. For a general random variable, the Bernoulli component may be defined so that its conditional variance is uniformly positive. The natural maximization problem is an optimal transport question which is also addressed here

Impact of Ceftolozane-Tazobactam vs. Best Alternative Therapy on Clinical Outcomes in Patients with Multidrug-Resistant and Extensively Drug-Resistant Pseudomonas aeruginosa Lower Respiratory Tract Infections

INTRODUCTION: Infections caused by multidrug-resistant (MDR), extensively drug-resistant (XDR), and difficult-to-treat (DTR) Pseudomonas aeruginosa are increasingly challenging to combat. Ceftolozane-tazobactam (C/T) is a novel β-lactam-β-lactamase inhibitor combination now commonly used to treat MDR and XDR P. aeruginosa. Lower respiratory tract infections (LRTIs) remain the most common source of infection caused by MDR/XDR P. aeruginosa. Comparative effectiveness studies to date have been limited by the type of comparator agents (i.e., aminoglycosides and polymyxins) and the inclusion of multiple infection sources (i.e., urinary tract, abdominal, skin and soft tissue, etc.). METHODS: We performed a multicenter, retrospective analysis of adults with LRTI caused by MDR or XDR P. aeruginosa admitted from January 2014 to December 2019. We aimed to compare clinical outcomes between patients who received C/T (n = 118) versus best alternative therapy (n = 88). The primary outcome was clinical failure, defined as 30-day mortality and/or an adverse drug reaction on antibiotic therapy. RESULTS: Two hundred and six patients met inclusion criteria. The C/T group had a significantly higher proportion of XDR P. aeruginosa and ventilator-associated bacterial pneumonia (VABP). After multivariable logistic regression, C/T treatment was independently associated with a 73.3% reduction in clinical failure compared to those who received best alternative therapy (P \u3c 0.001). The number needed to harm with best alternative therapy was 3. CONCLUSION: Our results suggest that C/T is a safe and effective therapeutic regimen for patients with MDR and XDR P. aeruginosa LRTI

Functional Glycosylation of Dystroglycan Is Crucial for Thymocyte Development in the Mouse

BACKGROUND: Alpha-dystroglycan (alpha-DG) is a cell surface receptor providing a molecular link between the extracellular matrix (ECM) and the actin-based cytoskeleton. During its biosynthesis, alpha-DG undergoes specific and unusual O-glycosylation crucial for its function as a high-affinity cellular receptor for ECM proteins. METHODOLOGY/PRINCIPAL FINDINGS: We report that expression of functionally glycosylated alpha-DG during thymic development is tightly regulated in developing T cells and largely confined to CD4(-)CD8(-) double negative (DN) thymocytes. Ablation of DG in T cells had no effect on proliferation, migration or effector function but did reduce the size of the thymus due to a significant loss in absolute numbers of thymocytes. While numbers of DN thymocytes appeared normal, a marked reduction in CD4(+)CD8(+) double positive (DP) thymocytes occurred. In the periphery mature naïve T cells deficient in DG showed both normal proliferation in response to allogeneic cells and normal migration, effector and memory T cell function when tested in acute infection of mice with either lymphocytic choriomeningitis virus (LCMV) or influenza virus. CONCLUSIONS/SIGNIFICANCE: Our study demonstrates that DG function is modulated by glycosylation during T cell development in vivo and that DG is essential for normal development and differentiation of T cells

Correlative Light- and Electron Microscopy with chemical tags

AbstractCorrelative microscopy incorporates the specificity of fluorescent protein labeling into high-resolution electron micrographs. Several approaches exist for correlative microscopy, most of which have used the green fluorescent protein (GFP) as the label for light microscopy. Here we use chemical tagging and synthetic fluorophores instead, in order to achieve protein-specific labeling, and to perform multicolor imaging. We show that synthetic fluorophores preserve their post-embedding fluorescence in the presence of uranyl acetate. Post-embedding fluorescence is of such quality that the specimen can be prepared with identical protocols for scanning electron microscopy (SEM) and transmission electron microscopy (TEM); this is particularly valuable when singular or otherwise difficult samples are examined. We show that synthetic fluorophores give bright, well-resolved signals in super-resolution light microscopy, enabling us to superimpose light microscopic images with a precision of up to 25nm in the x–y plane on electron micrographs. To exemplify the preservation quality of our new method we visualize the molecular arrangement of cadherins in adherens junctions of mouse epithelial cells