Information Costs and Reverse Payment Settlements: Bridging the Gap Between the Courts and the Antitrust Agencies

Reverse payment settlements have attracted increased scrutiny due to the controversial presence of a payment from a brand-name drug company to a generic company that is ostensibly preparing to infringe on the branded company’s patent. The antitrust agencies and the courts settled into an intergovernmental stalemate regarding the appropriate framework of analysis to apply when reviewing antitrust challenges to these settlements. The FTC and DOJ have viewed the deals skeptically as a vehicle for competitors to split monopoly profits, but the lower courts have generally been deferential to what they identified as an exercise of a patent holder’s lawful right to exclude. Much has been written about which side is correct, yet there has been relatively little exploration of the source of the persistent disagreement. Building off of Henry Smith’s property rights theory and the cognitive miser literature from Peter Lee, this Article explains that the long-standing disagreement stems from the judiciary’s application of information-cost-saving rules. Courts adopted a formalistic approach that would almost invariably uphold a reverse payment settlement because they tend to apply bright-line rules when dealing with property rights, and they are prone to adjudicate complex patent and patent-related cases in ways that economize on the costs of information processing. Although the Supreme Court resolved the disagreement by adopting a more information-demanding rule of reason approach in FTC v. Actavis, the cognitive miser phenomenon will continue to affect how courts adjudicate antitrust challenges to reverse-payment settlements

My Dream of the USA

VERSE 1A soldier in camp lay dreaming,Dreaming of his native land,He saw her noble statesmanAnd blood-stained heroes, grand;He saw her soldiers and sailorsAnd the boys in Blue and Gray;At dawn unto his comrades,These words I heard him say: CHORUS“I saw Washington cross the Delaware,I saw Stark ‘mid Mountains Green;I saw Warren fight at Bunker Hill,Andrew Jackson at New Orleans;I saw Davy Crockett at the Alamo,Taylor fight at Monterey,And all fought for our liberty,In my dreams of the U. S. A. VERSE 2At Plymouth he saw the landingOf the gallant Pilgrim band,He heard a bell ring libertyAnd freedom thro’ the land;O’er battle fields he wandered,Where her heroes fought and fell;Then turning to his comrades,These words I heard him tell. CHORU

Interaction of reed and acoustic resonator in clarinetlike systems

Sound emergence in clarinetlike instruments is investigated in terms of instability of the static regime. Various models of reed-bore coupling are considered, from the pioneering work of Wilson and Beavers ["Operating modes of the clarinet", J. Acoust. Soc. Am. 56, 653--658 (1974)] to more recent modeling including viscothermal bore losses and vena contracta at the reed inlet. The pressure threshold above which these models may oscillate as well as the frequency of oscillation at threshold are calculated. In addition to Wilson and Beavers' previous conclusions concerning the role of the reed damping in the selection of the register the instrument will play on, the influence of the reed motion induced flow is also emphasized, particularly its effect on playing frequencies, contributing to reduce discrepancies between Wilson and Beavers' experimental results and theory, despite discrepancies still remain concerning the pressure threshold. Finally, analytical approximations of the oscillating solution based on Fourier series expansion are obtained in the vicinity of the threshold of oscillation. This allows to emphasize the conditions which determine the nature of the bifurcation (direct or inverse) through which the note may emerge, with therefore important consequences on the musical playing performances

Integrase-deficient lentiviral vectors mediate efficient gene transfer to human vascular smooth muscle cells with minimal genotoxic risk

We have previously shown that injury-induced neointima formation was rescued by adenoviral-Nogo-B gene delivery. Integrase-competent lentiviral vectors (ICLV) are efficient at gene delivery to vascular cells but present a risk of insertional mutagenesis. Conversely, integrase-deficient lentiviral vectors (IDLV) offer additional benefits through reduced mutagenesis risk, but this has not been evaluated in the context of vascular gene transfer. Here, we have investigated the performance and genetic safety of both counterparts in primary human vascular smooth muscle cells (VSMC) and compared gene transfer efficiency and assessed the genotoxic potential of ICLVs and IDLVs based on their integration frequency and insertional profile in the human genome. Expression of enhanced green fluorescent protein (eGFP) mediated by IDLVs (IDLV-eGFP) demonstrated efficient transgene expression in VSMCs. IDLV gene transfer of Nogo-B mediated efficient overexpression of Nogo-B in VSMCs, leading to phenotypic effects on VSMC migration and proliferation, similar to its ICLV version and unlike its eGFP control and uninfected VSMCs. Large-scale integration site analyses in VSMCs indicated that IDLV-mediated gene transfer gave rise to a very low frequency of genomic integration compared to ICLVs, revealing a close-to-random genomic distribution in VSMCs. This study demonstrates for the first time the potential of IDLVs for safe and efficient vascular gene transfer

An exploration of the lived experiences of people with alcohol related harm in Scotland

Background; Alcohol consumption has posed well documented problems for Scottish society, in terms of morbidity, mortality and wider societal costs. Objectives; To investigate the lived experiences and drinking behaviours of people with alcohol-related harm in Scotland, against a backdrop of recent economic downturn, falling incomes, welfare reform and changes to state benefits. Methods; As part of a larger Scottish study (2012-2014) of 639 individuals attending hospital or admitted, relating to an alcohol problem, 20 participants completed semi-structured interviews about their drinking and purchasing habits which were subjected to thematic analysis. Conclusions; Key themes elucidated participants' everyday drink-related behaviours within their local environment including drinking triggers, sourcing alcohol, resourcing alcohol purchase and views relating to substitution. The majority of participants had experienced reduced income, and adapted their alcohol purchasing behaviours accordingly, including 'trading down' to cheaper alcohol. A reduction in food purchasing and heating was a common outcome, as was falling into, or increasing current, debt. More attention should be paid to the prevalence and accessibility of alcohol within local communities. Ultimately, as long as there is highly visible and easily accessible cheap alcohol, heavy drinkers may struggle to undertake positive steps to reduce their damaging consumption levels.div_PaSAnderson, P., & Baumberg, B. (2006). Alcohol in Europe. A public health perspective: London: Institute of Alcohol Studies; 2006. Beeston, C., McAdams, R., Craig, N., Gordon, R., Graham, L., MacPherson, M., McAuley, A., McCartney, G., Robinson, M., Shipton, D., & Van Heelsum, A. (2016). Monitoring and Evaluating Scotland's Alcohol Strategy. Final Report. Edinburgh: NHS Health Scotland. Black, H., Gill, J., & Chick, J. 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Alcohol-related Hospital Statistics Scotland 2014/15. Edinburgh: Information and Statistics Division. Retrieved from http://www.isdscotland.org/Health-Topics/Drugs-and- 22 Alcohol-Misuse/Publications/2015-10-13/2015-10-13-ARHS2014-15-Report.pdf (last accessed 14 January 2016) Ludbrook, A., Petrie, D., McKenzie, L., & Farrar, S. (2012). Tackling alcohol misuse purchasing patterns affected by minimum pricing for alcohol. Applied Health Economics and Health Policy, 10(1), 51-63. MacNaughton, P., & Gillan, E. (2011). Re-thinking alcohol licensing. Edinburgh: Alcohol Focus Scotland/Scottish Health Action on Alcohol Problems. Makela, P., Herttua, K., & Martikainen, P. (2015). The socioeconomic differences in alcohol-related harm and the effects of alcohol prices on them: a summary of evidence from Finland. Alcohol and Alcoholism, 50(6), 661-669. Nakamura, R., Suhrcke, M., Pechey, R., Morciano, M., Roland, M., & Marteau, T.M. (2014a). Impact on alcohol purchasing of a ban on multi-buy promotions: a quasi-experimental evaluation comparing Scotland with England and Wales. Addiction 109(4): 558-567. Nakamura, R., Pechey, R., Suhrcke, M., Jebb, S., & Marteau, T. (2014b). Sales impact of displaying alcoholic and no-alcoholic beverages in end-of-aisle locations: an observational study. Social Science & Medicine 108: 68-73. ONS (2014). Office for National Statistics. Statistical Bulletin: Alcohol-related deaths in the United Kingdom, registered in 2012. Retrieved from http://www.ons.gov.uk/ons/dcp171778_353201.pdf (last accessed 14 January 2016). 23 O'May, F., Black, H., Gill, J., Rees, C., Chick, J., & McPake, B. (2016) Dependent drinkers' perspectives on minimum unit pricing for alcohol in Scotland: a qualitative interview study. SAGEOpen, DOI: 10.1177/2158244016657141. O'May F, Whittaker A, Black H and Gill J. (2016) The families and friends of heavy drinkers; caught in the cross fire of policy change? Drug and Alcohol Review 2016 Apr 13. doi: 10.1111/dar.12403. Orford, J., Velleman, R., Copello, A., Templeton, L. & Ibanga, A. (2010). The experiences of affected family members: a summary of two decades of qualitative research. Drug Education Prevention and Policy, 17, 44-62. Orford, J., Velleman, R., Natera, G., Templeton, L. & Coppello, A. (2013). Addiction in the family is a major but neglected contributor to the global burden of adult ill-health. Social Science & Medicine, 78, 70-77. Rice, P. (2014). Why do the health professions want minimum unit price in Scotland? In Proceedings of Scotland the Brave! - Alcohol Policy in Scotland, 5 September, 2014, Brussels. Retrieved from http://www.shaap.org.uk/images/mup-event-summary.pdf (last accessed 14 January 2016). Richardson, E.A., Hill, S.E., Mitchell,R., Pearce, J., & Shortt, N.K. (2015). Is local alcohol outlet density related to alcohol-related morbidity and mortality in Scottish cities? 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Multicentre phase II pharmacokinetic and pharmacodynamic study of OSI-7904L in previously untreated patients with advanced gastric or gastroesophageal junction adenocarcinoma

A two-stage Simon design was used to evaluate the response rate of OSI-7904L, a liposome encapsulated thymidylate synthase inhibitor, in advanced gastric and/or gastroesophageal adenocarcinoma (A-G/GEJA), administered intravenously at 12 mg m−2 over 30 min every 21 days. Fifty patients were treated. Median age was 64 years (range 35–82), 62% were male and 89% had ECOG PS of 0/1. A total of 252 cycles were administered; median of 4 per patient (range 1–21). Twelve patients required dose reductions, mainly for skin toxicity. Investigator assessed response rate was 17.4% (95% CI 7.8–31.4) with one complete and seven partial responses in 46 evaluable patients. Twenty-one patients (42%) had stable disease. Median time to progression and survival were 12.4 and 36.9 weeks, respectively. NCI CTCAE Grade 3/4 neutropenia (14%) and thrombocytopenia (4%) were uncommon. The main G3/4 nonhaematological toxicities were skin-related 22%, stomatitis 14%, fatigue/lethargy 10%, and diarrhea 8%. Pharmacokinetic data showed high interpatient variability. Patients with higher AUC were more likely to experience G3/4 toxicity during cycle 1 while baseline homocysteine did not predict toxicity. Response did not correlate with AUC. Elevations in 2′-dU were observed indicating target inhibition. Analysis of TS genotype, TS protein and expression did not reveal any correlation with outcome. OSI-7904L has activity in A-G/GEJA similar to other active agents and an acceptable safety profile

Long-term Survey and Assessment of Large-River Fishes in Illinois, 2018

This report presents a summary of those data collected during segment 30 (2018-2019) of the Long-term Survey and Assessment of Large-River Fishes in Illinois (LTEF), an annual survey by members of the Illinois Natural History Survey, with funds administered by the U.S. Fish and Wildlife Service and the Illinois Department of Natural Resources. Sampling for the LTEF program was conducted on: six reaches of the Illinois River Waterway and four segments or pools of the Mississippi River. In all segments of the LTEF program, all fish species collected were accurately identified, tallied, measured, and weighed. The catch rates of sportfish species were calculated as the number of individuals collected per hour (CPUEN ± standard error). Structural indices [Proportional Size Distribution (PSD) and Relative Weight (Wr)] were also calculated for several species of interest to regional managers. Catch rates and species varied among all sampling locations and sampling periods. Gizzard Shad and Emerald Shiners comprised the majority of the individuals caught, and Silver Carp and Common Carp accounted for the greatest proportion of the biomass collected in most sampling areas of the survey. Future analysis of CPUEN and PSD trends in sportfish populations sampled by the program may indicate inter-annual recruitment patterns or/and long-term trends in Illinois sportfish populations.U.S. Fish and Wildlife ServiceIllinois Department of Natural Resources, Division of Fisheriesunpublishednot peer reviewedOpe

Feasibility of tumour-focused adaptive radiotherapy for bladder cancer on the MR-linac.

Bladder tumour-focused magnetic resonance image-guided adaptive radiotherapy using a 1.5 Tesla MR-linac is feasible. A full online workflow adapting to anatomy at each fraction is achievable in approximately 30 min. Intra-fraction bladder filling did not compromise target coverage with the class solution employed

Daily adaptive radiotherapy for patients with prostate cancer using a high field MR-linac: Initial clinical experiences and assessment of delivered doses compared to a C-arm linac.

Introduction:MR-guided adapted radiotherapy (MRgART) using a high field MR-linac has recently become available. We report the estimated delivered fractional dose of the first five prostate cancer patients treated at our centre using MRgART and compare this to C-Arm linac daily Image Guided Radiotherapy (IGRT). Methods:Patients were treated using adapted treatment plans shaped to their daily anatomy. The treatments were recalculated on an MR image acquired immediately prior to treatment delivery in order to estimate the delivered fractional dose. C-arm linac non-adapted VMAT treatment plans were recalculated on the same MR images to estimate the fractional dose that would have been delivered using conventional radiotherapy techniques using a daily IGRT protocol. Results:95% and 93% of mandatory target coverage objectives and organ at risk dose constraints were achieved by MRgART and C-arm linac delivered dose estimates, respectively. Both delivery techniques were estimated to have achieved 98% of mandatory Organ At Risk (OAR) dose constraints whereas for the target clinical goals, 86% and 80% were achieved by MRgART and C-arm linac delivered dose estimates. Conclusions:Prostate MRgART can be delivered using the a high field MR-linac. Radiotherapy performed on a C-arm linac offers a good solution for prostate cancer patients who present with favourable anatomy at the time of reference imaging and demonstrate stable anatomy throughout the course of their treatment. For patients with critical OARs abutting target volumes on their reference image we have demonstrated the potential for a target dose coverage improvement for MRgART compared to C-arm linac treatment