Prospective Overruling and the Revival of ‘Unconstitutional\u27 Statutes

The Supreme Court\u27s decision in Planned Parenthood v. Casey reshaped the law of abortion in this country. The Court overturned two of its previous decisions invalidating state restrictions on abortions, Thornburgh v. American College of Obstetricians and Gynecologists and Akron v. Akron Center for Reproductive Health, and it abandoned the trimester analytic framework established in Roe v. Wade. At the time Casey was handed down, twenty states had restrictive abortion statutes on the books that were in conflict with Akron or Thornburgh and which were unenforced. In six of these states, courts had held the statutes unconstitutional. Almost as soon as the Casey ruling was announced, the campaign to secure enforcement of these restrictions began. Are these statutes good law, despite the fact that they were once in conflict with governing Supreme Court precedent (and in some cases had been judicially determined to violate women\u27s constitutional rights)? Alternatively, will they have to be re-enacted by the legislature to be enforceable? These questions highlight the revival issue. The revival issue arises when a court overrules a prior decision in which it had held a statute unconstitutional. (We will throughout this article refer to the first decision as the invalidating decision, and to the second decision as the overruling decision. ) Should the enforceability of a statute passed prior to the overruling decision be determined by reference to the invalidating decision--in which case the statute would have to be repassed to be in effect--or by reference to the overruling decision--in which case the statute would not have to be repassed? In other words, does the overruling decision automatically revive a previously unenforceable statute? The way in which the revival issue is resolved will thus determine whether, in light of Casey, previously unenforced statutes became enforceable without the need for any post-Casey legislative action. In addition to affecting what kind of abortion regulations are in effect in twenty states in the immediate wake of Casey, this determination has profound consequences for the kind of abortion regulations that will be in effect in these states in the future. Such long-term consequences reflect the fact that our governmental system is not one of pure majoritarianism and that the burden of inertia in our legislative process is heavy: as we will discuss, statutes on the books can stay on the books even if a current majority no longer desires them; in contrast, proposed statutes need supermajoritarian support to secure passage. Therefore, the starting point for future legislative action--such as whether pre-Casey abortion regulations are enforceable--influences the legislative action that in fact develops

Effect of display resolution on time to diagnosis with virtual pathology slides in a systematic search task

Performing diagnoses using virtual slides can take pathologists significantly longer than with glass slides, presenting a significant barrier to the use of virtual slides in routine practice. Given the benefits in pathology workflow efficiency and safety that virtual slides promise, it is important to understand reasons for this difference and identify opportunities for improvement. The effect of display resolution on time to diagnosis with virtual slides has not previously been explored. The aim of this study was to assess the effect of display resolution on time to diagnosis with virtual slides. Nine pathologists participated in a counterbalanced crossover study, viewing axillary lymph node slides on a microscope, a 23-in 2.3-megapixel single-screen display and a three-screen 11-megapixel display consisting of three 27-in displays. Time to diagnosis and time to first target were faster on the microscope than on the single and three-screen displays. There was no significant difference between the microscope and the three-screen display in time to first target, while the time taken on the single-screen display was significantly higher than that on the microscope. The results suggest that a digital pathology workstation with an increased number of pixels may make it easier to identify where cancer is located in the initial slide overview, enabling quick location of diagnostically relevant regions of interest. However, when a comprehensive, detailed search of a slide has to be made, increased resolution may not offer any additional benefit

What works where and how for uptake and impact of artificial intelligence in pathology: Review of theories for a realist evaluation

YesThere is increasing interest in the use of artificial intelligence (AI) in pathology to increase accuracy and efficiency. To date, studies of clinicians' perceptions of AI have found only moderate acceptability, suggesting the need for further research regarding how to integrate it into clinical practice. The aim of the study was to determine contextual factors that may support or constrain the uptake of AI in pathology. To go beyond a simple listing of barriers and facilitators, we drew on the approach of realist evaluation and undertook a review of the literature to elicit stakeholders' theories of how, for whom, and in what circumstances AI can provide benefit in pathology. Searches were designed by an information specialist and peer-reviewed by a second information specialist. Searches were run on the arXiv.org repository, MEDLINE, and the Health Management Information Consortium, with additional searches undertaken on a range of websites to identify gray literature. In line with a realist approach, we also made use of relevant theory. Included documents were indexed in NVivo 12, using codes to capture different contexts, mechanisms, and outcomes that could affect the introduction of AI in pathology. Coded data were used to produce narrative summaries of each of the identified contexts, mechanisms, and outcomes, which were then translated into theories in the form of context-mechanism-outcome configurations. A total of 101 relevant documents were identified. Our analysis indicates that the benefits that can be achieved will vary according to the size and nature of the pathology department's workload and the extent to which pathologists work collaboratively; the major perceived benefit for specialist centers is in reducing workload. For uptake of AI, pathologists' trust is essential. Existing theories suggest that if pathologists are able to "make sense" of AI, engage in the adoption process, receive support in adapting their work processes, and can identify potential benefits to its introduction, it is more likely to be accepted. For uptake of AI in pathology, for all but the most simple quantitative tasks, measures will be required that either increase confidence in the system or provide users with an understanding of the performance of the system. For specialist centers, efforts should focus on reducing workload rather than increasing accuracy. Designers also need to give careful thought to usability and how AI is integrated into pathologists' workflow

Antithrombin activity of fucoidan. The interaction of fucoidan with heparin cofactor II, antithrombin III, and thrombin

Fucoidan, poly(L-fucopyranose) linked primarily alpha 1----2 with either a C3- or a C4-sulfate, is an effective anticoagulant in vitro and in vivo (Springer, G. F., Wurzel, H. A., McNeal, G. M., Jr., Ansell, N. J., and Doughty, M. F. (1957) Proc. Soc. Exp. Biol. Med. 94, 404-409). We have determined the antithrombin effects of fucoidan on the glycosaminoglycan-binding plasma proteinase inhibitors antithrombin III and heparin cofactor II. Fucoidan enhances the heparin cofactor II-thrombin reaction more than 3500-fold. The apparent second-order rate constant of thrombin inhibition by heparin cofactor II increases from 4 x 10(4) (in the absence of fucoidan) to 1.5 x 10(8) M-1 min-1 as the fucoidan concentration increases from 0.1 to 10 micrograms/ml and then decreases as fucoidan is increased above 10 micrograms/ml. The fucoidan reaction with heparin cofactor II-thrombin is kinetically equivalent to a "template model." Apparent fucoidan-heparin cofactor II and fucoidan-thrombin dissociation constants are 370 and 1 nM, respectively. The enhancement of thrombin inhibition by fucoidan, like heparin and dermatan sulfate, is eliminated by selective chemical modification of lysyl residues either of heparin cofactor II or of thrombin. The fucoidan-antithrombin III reactions with thrombin and factor Xa are accelerated maximally 285- and 35-fold at fucoidan concentrations of 30 and 500 micrograms/ml, respectively. Using human plasma and 125I-labeled thrombin in an ex vivo system, the heparin cofactor II-thrombin complex is formed preferentially over the antithrombin III-thrombin complex in the presence of 10 micrograms/ml fucoidan. Our results indicate that heparin cofactor II is activated by fucoidan in vitro and in an ex vivo plasma system and suggest that the major antithrombin activity of fucoidan in vivo is mediated by heparin cofactor II and not by antithrombin III

Ezrin interacts with the SARS coronavirus spike protein and restrains infection at the entry stage

© 2012 Millet et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: Entry of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) and its envelope fusion with host cell membrane are controlled by a series of complex molecular mechanisms, largely dependent on the viral envelope glycoprotein Spike (S). There are still many unknowns on the implication of cellular factors that regulate the entry process. Methodology/Principal Findings: We performed a yeast two-hybrid screen using as bait the carboxy-terminal endodomain of S, which faces the cytosol during and after opening of the fusion pore at early stages of the virus life cycle. Here we show that the ezrin membrane-actin linker interacts with S endodomain through the F1 lobe of its FERM domain and that both the eight carboxy-terminal amino-acids and a membrane-proximal cysteine cluster of S endodomain are important for this interaction in vitro. Interestingly, we found that ezrin is present at the site of entry of S-pseudotyped lentiviral particles in Vero E6 cells. Targeting ezrin function by small interfering RNA increased S-mediated entry of pseudotyped particles in epithelial cells. Furthermore, deletion of the eight carboxy-terminal amino acids of S enhanced S-pseudotyped particles infection. Expression of the ezrin dominant negative FERM domain enhanced cell susceptibility to infection by SARS-CoV and S pseudotyped particles and potentiated S-dependent membrane fusion. Conclusions/Significance: Ezrin interacts with SARS-CoV S endodomain and limits virus entry and fusion. Our data present a novel mechanism involving a cellular factor in the regulation of S-dependent early events of infection.This work was supported by the Research Grant Council of Hong Kong (RGC#760208)and the RESPARI project of the International Network of Pasteur Institutes

Rigid Chiral Membranes

Statistical ensembles of flexible two-dimensional fluid membranes arise naturally in the description of many physical systems. Typically one encounters such systems in a regime of low tension but high stiffness against bending, which is just the opposite of the regime described by the Polyakov string. We study a class of couplings between membrane shape and in-plane order which break 3-space parity invariance. Remarkably there is only {\it one} such allowed coupling (up to boundary terms); this term will be present for any lipid bilayer composed of tilted chiral molecules. We calculate the renormalization-group behavior of this relevant coupling in a simplified model and show how thermal fluctuations effectively reduce it in the infrared.Comment: 11 pages, UPR-518T (This replaced version has fonts not used removed.

Theory of Cylindrical Tubules and Helical Ribbons of Chiral Lipid Membranes

We present a general theory for the equilibrium structure of cylindrical tubules and helical ribbons of chiral lipid membranes. This theory is based on a continuum elastic free energy that permits variations in the direction of molecular tilt and in the curvature of the membrane. The theory shows that the formation of tubules and helical ribbons is driven by the chirality of the membrane. Tubules have a first-order transition from a uniform state to a helically modulated state, with periodic stripes in the tilt direction and ripples in the curvature. Helical ribbons can be stable structures, or they can be unstable intermediate states in the formation of tubules.Comment: 43 pages, including 12 postscript figures, uses REVTeX 3.0 and epsf.st

Safety, efficacy, and immunogenicity of an inactivated influenza vaccine in healthy adults: a randomized, placebo-controlled trial over two influenza seasons

<p>Abstract</p> <p>Background</p> <p>Seasonal influenza imposes a substantial personal morbidity and societal cost burden. Vaccination is the major strategy for influenza prevention; however, because antigenically drifted influenza A and B viruses circulate annually, influenza vaccines must be updated to provide protection against the predicted prevalent strains for the next influenza season. The aim of this study was to assess the efficacy, safety, reactogenicity, and immunogenicity of a trivalent inactivated split virion influenza vaccine (TIV) in healthy adults over two influenza seasons in the US.</p> <p>Methods</p> <p>The primary endpoint of this double-blind, randomized study was the average efficacy of TIV versus placebo for the prevention of vaccine-matched, culture-confirmed influenza (VMCCI) across the 2005-2006 and 2006-2007 influenza seasons. Secondary endpoints included the prevention of laboratory-confirmed (defined by culture and/or serology) influenza, as well as safety, reactogenicity, immunogenicity, and consistency between three consecutive vaccine lots. Participants were assessed actively during both influenza seasons, and nasopharyngeal swabs were collected for viral culture from individuals with influenza-like illness. Blood specimens were obtained for serology one month after vaccination and at the end of each influenza season's surveillance period.</p> <p>Results</p> <p>Although the point estimate for efficacy in the prevention of all laboratory-confirmed influenza was 63.2% (97.5% confidence interval [CI] lower bound of 48.2%), the point estimate for the primary endpoint, efficacy of TIV against VMCCI across both influenza seasons, was 46.3% with a 97.5% CI lower bound of 9.8%. This did not satisfy the pre-specified success criterion of a one-sided 97.5% CI lower bound of >35% for vaccine efficacy. The VMCCI attack rates were very low overall at 0.6% and 1.2% in the TIV and placebo groups, respectively. Apart from a mismatch for influenza B virus lineage in 2005-2006, there was a good match between TIV and the circulating strains. TIV was highly immunogenic, and immune responses were consistent between three different TIV lots. The most common reactogenicity events and spontaneous adverse events were associated with the injection site, and were mild in severity.</p> <p>Conclusions</p> <p>Despite a good immune response, and an average efficacy over two influenza seasons against laboratory-confirmed influenza of 63.2%, the pre-specified target (lower one-sided 97.5% confidence bound for efficacy > 35%) for the primary efficacy endpoint, the prevention of VMCCI, was not met. However, the results should be interpreted with caution in view of the very low attack rates we observed at the study sites in the 2005-2006 and 2006-2007, which corresponded to relatively mild influenza seasons in the US. Overall, the results showed that TIV has an acceptable safety profile and offered clinical benefit that exceeded risk.</p> <p>Trial registration</p> <p>NCT00216242</p

Consistency and Standardization of Color in Medical Imaging: a Consensus Report

This article summarizes the consensus reached at the Summit on Color in Medical Imaging held at the Food and Drug Administration (FDA) on May 8–9, 2013, co-sponsored by the FDA and ICC (International Color Consortium). The purpose of the meeting was to gather information on how color is currently handled by medical imaging systems to identify areas where there is a need for improvement, to define objective requirements, and to facilitate consensus development of best practices. Participants were asked to identify areas of concern and unmet needs. This summary documents the topics that were discussed at the meeting and recommendations that were made by the participants. Key areas identified where improvements in color would provide immediate tangible benefits were those of digital microscopy, telemedicine, medical photography (particularly ophthalmic and dental photography), and display calibration. Work in these and other related areas has been started within several professional groups, including the creation of the ICC Medical Imaging Working Group

A new multicompartmental reaction-diffusion modeling method links transient membrane attachment of E. coli MinE to E-ring formation

Many important cellular processes are regulated by reaction-diffusion (RD) of molecules that takes place both in the cytoplasm and on the membrane. To model and analyze such multicompartmental processes, we developed a lattice-based Monte Carlo method, Spatiocyte that supports RD in volume and surface compartments at single molecule resolution. Stochasticity in RD and the excluded volume effect brought by intracellular molecular crowding, both of which can significantly affect RD and thus, cellular processes, are also supported. We verified the method by comparing simulation results of diffusion, irreversible and reversible reactions with the predicted analytical and best available numerical solutions. Moreover, to directly compare the localization patterns of molecules in fluorescence microscopy images with simulation, we devised a visualization method that mimics the microphotography process by showing the trajectory of simulated molecules averaged according to the camera exposure time. In the rod-shaped bacterium _Escherichia coli_, the division site is suppressed at the cell poles by periodic pole-to-pole oscillations of the Min proteins (MinC, MinD and MinE) arising from carefully orchestrated RD in both cytoplasm and membrane compartments. Using Spatiocyte we could model and reproduce the _in vivo_ MinDE localization dynamics by accounting for the established properties of MinE. Our results suggest that the MinE ring, which is essential in preventing polar septation, is largely composed of MinE that is transiently attached to the membrane independently after recruited by MinD. Overall, Spatiocyte allows simulation and visualization of complex spatial and reaction-diffusion mediated cellular processes in volumes and surfaces. As we showed, it can potentially provide mechanistic insights otherwise difficult to obtain experimentally