Unintended Consequences and Intended Non-Consequences

The idea that government policies have unintended consequences has become a fixture of political argument, indeed a cliché. One can hardly get through a day’s newspaper editorials without encountering it with respect to something in the news—the TARP bailouts, the North Korea bailouts, executive pay caps, local issues such as the drinking age and the driving age.

Rationalism in Regulation

This Review follows the structure of Retaking Rationality. In Part I we criticize the book’s narrative (summarized above) as cartoonish and unhistorical—we think it is confusing rather than helpful to understanding recent developments and controversies in cost-benefit analysis and the organization of regulatory decisionmaking within the executive branch. In Part II we consider the book’s “Eight Fallacies of Cost-Benefit Analysis.” We find that these discussions are generally well informed and interesting but suffer from the effort to squeeze cost-benefit issues into the antiregulation-versusproregulation narrative; moreover the discussions are often excessively abstract and ambitious concerning the function of cost-benefit analysis, and they entirely fail to support the thesis that cost-benefit fallacies have been used to defeat beneficial regulations. Finally, in Part III we discuss the authors’ arguments about the need for and practice of OMB/OIRA oversight of agency rulemaking. Here we criticize as naïve the book’s argument that there is no need for an institutional counterweight to agency parochialism and that OIRA’s role should be recast as one of coordination, calibration, and promotion of a proregulatory agenda against the forces of agency sloth. A concluding Part sums up our arguments.

The Case Against Credit Card Interest Rate Regulation

This article analyzes recent proposals to regulate credit card interest rates on a national scale. The proposals are a modern chapter in a very old story. Usury laws-laws forbidding or limiting payment for money loans-are among the most ancient forms of price control. Like previous economic studies of usury controls, this one concludes that they are unjustified because the supply of credit is highly competitive, and would be harmful because they would cause an artificial contraction in the supply of credit and other economic inefficiencies

The clinical profile of tuberous sclerosis complex (TSC) in the United Kingdom: A retrospective cohort study in the Clinical Practice Research Datalink (CPRD)

AbstractBackgroundTuberous Sclerosis Complex (TSC) is a multi-system genetic disorder characterised by the development of benign growths and diverse clinical manifestations, varying in severity, age at onset and with high clinical burden.AimsThis longitudinal study aims to describe the broad spectrum of clinical manifestation profiles in a large, representative cohort of TSC patients in the UK in order to better understand disease complexity.MethodsTSC patients in the Clinical Practice Research Datalink (CPRD) and linked Hospital Episodes Statistics (CPRD-HES) were retrospectively identified between 1987 and 2013. Available history was extracted for each patient and clinical diagnosis, procedure and medication records reviewed. A random selection of patients from the CPRD-HES was used as a Comparator cohort.ResultsThree hundred and thirty-four TSC patients with a mean (SD) age of 30.3 (18.6) years were identified (53% female). TSC was diagnosed at mean age 3.2 (4.2) years. Epilepsy and psychiatric manifestations were reported frequently in paediatric (77% and 55%, respectively) and adult patients (66% and 68%, respectively). The prevalence of manifestations in the TSC cohort was markedly higher versus the Comparator cohort. The majority of paediatric (46%) and adult TSC patients (62%) developed clinical manifestations affecting at least three organ systems and forty-nine distinctive organ system manifestation profiles were identified.ConclusionsTSC patients present with multiple and complex clinical manifestations and profiles that necessitate the co-ordinated action of a multidisciplinary team in order to improve the quality and efficiency of care

‘Bell’ Pear

‘Bell’ (Pyrus communis L.) is an early-season pear variety that combines fire blight resistance with exceptional flavor and high productivity. Fire blight, caused by the bacterial pathogen Erwinia amylovora, is a devastating disease for pear growers in the mid-Atlantic region and other pear production areas prone to hot and humid climates. ‘Bell’ has exhibited strong resistance to natural infection by Erwinia compared with the susceptible, industry-standard ‘Bartlett’. ‘Bell’ also exhibits a “balanced” sugar and acidity content that is desirable and preferred by pear consumers. The US Department of Agriculture and Pennsylvania State University released ‘Bell’ in 2022 as a fresh-market pear for commercial, direct-to-market, and home production

QUINT: Workflow for Quantification and Spatial Analysis of Features in Histological Images From Rodent Brain

Transgenic animal models are invaluable research tools for elucidating the pathways and mechanisms involved in the development of neurodegenerative diseases. Mechanistic clues can be revealed by applying labelling techniques such as immunohistochemistry or in situ hybridisation to brain tissue sections. Precision in both assigning anatomical location to the sections and quantifying labelled features is crucial for output validity, with a stereological approach or image-based feature extraction typically used. However, both approaches are restricted by the need to manually delineate anatomical regions. To circumvent this limitation, we present the QUINT workflow for quantification and spatial analysis of labelling in series of rodent brain section images based on available 3D reference atlases. The workflow is semi-automated, combining three open source software that can be operated without scripting knowledge, making it accessible to most researchers. As an example, a brain region-specific quantification of amyloid plaques across whole transgenic Tg2576 mouse brain series, immunohistochemically labelled for three amyloid-related antigens is demonstrated. First, the whole brain image series were registered to the Allen Mouse Brain Atlas to produce customised atlas maps adapted to match the cutting plan and proportions of the sections (QuickNII software). Second, the labelling was segmented from the original images by the Random Forest Algorithm for supervised classification (ilastik software). Finally, the segmented images and atlas maps were used to generate plaque quantifications for each region in the reference atlas (Nutil software). The method yielded comparable results to manual delineations and to the output of a stereological method. While the use case demonstrates the QUINT workflow for quantification of amyloid plaques only, the workflow is suited to all mouse or rat brain series with labelling that is visually distinct from the background, for example for the quantification of cells or labelled proteins

More Than Forty Prominent Economists Urge Supreme Court to Allow EPA to Consider Costs and Consequences of Clean Air Regulations

More than forty prominent economists filed a Friend of the Court brief with the Supreme Court, asking the justices to overturn a lower court ruling that the Environmental Protection Agency (EPA) may not take into account the costs of regulations when setting standards under the Clean Air Act. Calling the lower court ruling "economically unsound," the economists argued that the EPA "should be allowed to consider explicitly the full consequences" of regulatory decisions, including costs, benefits, and any other relevant facts. In their Amici Curiae brief, the economists contended that the "plain aim" of the Clean Air Act "is protecting the public health&quo.t; That aim, they said, "is unlikely to be achieved without, at least, an implicit balancing of benefits and costs." The Supreme Court filing was organized by the American Enterprise Institute-Brookings Joint Center for Regulatory Studies. The bipartisan group of economists signing the brief included three Nobel laureates, seven former chairmen of the President's Council of Economic Advisers, and two former directors of the White House Office of Management and Budget. The case, American Trucking Association v. Carol M. Browner, Administrator of the Environmental Protection Agency , was appealed to the Supreme Court after a Federal Court in Washington D.C. ruled that the EPA was not permitted to consider costs in setting regulatory standards for enforcing the Clean Air Act. "We believe it would be imprudent for the EPA to ignore costs totally, particularly given their magnitude in this case," the economists stated in the brief. "The EPA estimates that those [clean air] standards could cost on the order of $50 billion annually." The brief argued, "Not considering costs makes it difficult to set a defensible standard, especially when there is no threshold below which health risks disappear." Ignoring costs, the economists said, "could lead to a decision to set the standard at zero pollution," which would threaten "the very economic prosperity on which public health primarily depends." The economists declared: "The importance of this issue cannot be overstated. Both direct benefits and costs of environmental, health, and safety regulations are substantial, estimated to be several hundred billion dollars annually." If the Supreme Court overturns the lower court ruling and allows the EPA to consider costs in establishing clear air regulations, the brief argued, it would be "a historic moment in the making of regulatory policy."Environment, Other Topics

Mouse SLX4 Is a Tumor Suppressor that Stimulates the Activity of the Nuclease XPF-ERCC1 in DNA Crosslink Repair

SLX4 binds to three nucleases (XPF-ERCC1, MUS81-EME1, and SLX1), and its deficiency leads to genomic instability, sensitivity to DNA crosslinking agents, and Fanconi anemia. However, it is not understood how SLX4 and its associated nucleases act in DNA crosslink repair. Here, we uncover consequences of mouse Slx4 deficiency and reveal its function in DNA crosslink repair. Slx4-deficient mice develop epithelial cancers and have a contracted hematopoietic stem cell pool. The N-terminal domain of SLX4 (mini-SLX4) that only binds to XPF-ERCC1 is sufficient to confer resistance to DNA crosslinking agents. Recombinant mini-SLX4 enhances XPF-ERCC1 nuclease activity up to 100-fold, directing specificity toward DNA forks. Mini-SLX4-XPF-ERCC1 also vigorously stimulates dual incisions around a DNA crosslink embedded in a synthetic replication fork, an essential step in the repair of this lesion. These observations define vertebrate SLX4 as a tumor suppressor, which activates XPF-ERCC1 nuclease specificity in DNA crosslink repairope

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure