Tracking the Evolution of Stare Decisis

At the United States Supreme Court, what is old is new again. In a series of recent opinions,1 the justices have repeatedly offered differing views on how stare decisis should be positioned when tasked with justifying or rejecting existing precedent. Indeed, in three recent Supreme Court decisions the justices have wrestled with the effect of stare decisis on future decisions. Reversing a decision, according to Justice Kagan, “demand[s] a ‘special justification.’” In contrast, Justice Thomas posited that “[w]hen faced with demonstrably erroneous precedent, my rule is simple: We should not follow it.” Chief Justice Roberts, in explaining his switch in direction from a prior dissent, concluded that “[t]he legal doctrine of stare decisis requires us, absent special circumstances, to treat like cases alike.” The result is that some precedent is retained while other precedent is discarded, which ensues the debate over whether the justices “practice what they preach.

A Framework for Providing Research Applications as a Service Using the IOME Toolkit

This paper presents a unique, multi-purpose toolkit, enabling researchers to easily develop modelling and analysis applications, which can be run as web services and accessed interactively. The development kit is based on a protocol that uses an XML markup called the "Interactive Object Management Environment Markup Language" (IOME ML). The paper describes the IOME ML and its development kit. We illustrate the capabilities of IOME with two case studies the first case study is based on a medical image processing application (CAIMAN: CAncer IMage ANalysis), offering image analysis tools for life scientists. For the second case study, the Pi-Phi collaboration have developed an inverse imaging method for ‘lensless’ microscopy a demonstrator is introduced for the Pi-Phi project. For both case studies the application is wrapped as a web service and accessed through a web browser. The paper concludes with a review of further developments, including refinements to the mark up language and the development of a service factory, enabling a more scalable service provision model through the dynamic invocation of published simulations as IOME web service applications

Background Radioactivity in the Decorah Fault Region

A known fault site at Decorah, Iowa, was surveyed for indicative variations in surface radioactivity. A portable ionization chamber revealed significant increases in gamma ray intensity at several locations. At one point the radiation level was 70% greater than the background intensity. Measurements repeated one year later verified this pattern. Radiation contours were plotted over an extensive area in the city of Decorah. This map, with other items of supporting evidence, indicated a possible fault strike of approximately N 55° W

Fine Tuning in One-Higgs and Two-Higgs Standard Models

The fine-tuning principles are examined to predict the top-quark and Higgs-boson masses. The modification of the Veltman condition based on the compensation of vacuum energies is developed. It is implemented in the Standard Model and in its minimal extension with two Higgs doublets. The top-quark and Higgs-boson couplings are fitted in the SM for the lowest ultraviolet scale where the fine-tuning can be stable under rescaling. It yields the low-energy values $m_t \simeq 175 GeV; m_H \simeq 210 GeV$.Comment: 13 pages, LaTeX, Preprint PITHA-94-23 (July 1993

Bias in trials comparing paired continuous tests can cause researchers to choose the wrong screening modality

<p>Abstract</p> <p>Background</p> <p>To compare the diagnostic accuracy of two continuous screening tests, a common approach is to test the difference between the areas under the receiver operating characteristic (ROC) curves. After study participants are screened with both screening tests, the disease status is determined as accurately as possible, either by an invasive, sensitive and specific secondary test, or by a less invasive, but less sensitive approach. For most participants, disease status is approximated through the less sensitive approach. The invasive test must be limited to the fraction of the participants whose results on either or both screening tests exceed a threshold of suspicion, or who develop signs and symptoms of the disease after the initial screening tests.</p> <p>The limitations of this study design lead to a bias in the ROC curves we call <it>paired screening trial bias</it>. This bias reflects the synergistic effects of inappropriate reference standard bias, differential verification bias, and partial verification bias. The absence of a gold reference standard leads to inappropriate reference standard bias. When different reference standards are used to ascertain disease status, it creates differential verification bias. When only suspicious screening test scores trigger a sensitive and specific secondary test, the result is a form of partial verification bias.</p> <p>Methods</p> <p>For paired screening tests with bivariate normally distributed scores, we give formulae and programs to quantify the effect of <it>paired screening trial bias </it>on a paired comparison of area under the curves. We fix the prevalence of disease, and the chance a diseased subject manifests signs and symptoms. We derive the formulas for true sensitivity and specificity, and those for the sensitivity and specificity observed by the study investigator.</p> <p>Results</p> <p>The observed area under the ROC curves is quite different from the true area under the ROC curves. The typical direction of the bias is a strong inflation in sensitivity, paired with a concomitant slight deflation of specificity.</p> <p>Conclusion</p> <p>In paired trials of screening tests, when area under the ROC curve is used as the metric, bias may lead researchers to make the wrong decision as to which screening test is better.</p

Dual-Labeling Strategies for Nuclear and Fluorescence Molecular Imaging: A Review and Analysis

Molecular imaging is used for the detection of biochemical processes through the development of target-specific contrast agents. Separately, modalities such as nuclear and near-infrared fluorescence (NIRF) imaging have been shown to non-invasively monitor disease. More recently, merging of these modalities has shown promise owing to their comparable detection sensitivity and benefited from the development of dual-labeled imaging agents. Dual-labeled agents hold promise for whole-body and intraoperative imaging and could bridge the gap between surgical planning and image-guided resection with a single, molecularly targeted agent. In this review, we summarized the literature for dual-labeled antibodies and peptides that have been developed and have highlighted key considerations for incorporating NIRF dyes into nuclear labeling strategies. We also summarized our findings on several commercially available NIRF dyes and offer perspectives for developing a toolkit to select the optimal NIRF dye and radiometal combination for multimodality imaging

Atrophy of primary lymphoid organs induced by Marek's disease virus during early infection is associated with increased apoptosis, inhibition of cell proliferation and a severe B-lymphopenia

Marek's disease is a multi-faceted highly contagious disease affecting chickens caused by the Marek's disease alphaherpesvirus (MDV). MDV early infection induces a transient immunosuppression, which is associated with thymus and bursa of Fabricius atrophy. Little is known about the cellular processes involved in primary lymphoid organ atrophy. Here, by in situ TUNEL assay, we demonstrate that MDV infection results in a high level of apoptosis in the thymus and bursa of Fabricius, which is concomitant to the MDV lytic cycle. Interestingly, we observed that in the thymus most of the MDV infected cells at 6 days post-infection (dpi) were apoptotic, whereas in the bursa of Fabricius most of the apoptotic cells were uninfected suggesting that MDV triggers apoptosis by two different modes in these two primary lymphoid organs. In addition, a high decrease of cell proliferation was observed from 6 to 14 dpi in the bursa of Fabricius follicles, and not in the thymus. Finally, with an adapted absolute blood lymphocyte count, we demonstrate a major B-lymphopenia during the two 1st weeks of infection, and propose this method as a potent non-invasive tool to diagnose MDV bursa of Fabricius infection and atrophy. Our results demonstrate that the thymus and bursa of Fabricius atrophies are related to different cell mechanisms, with different temporalities, that affect infected and uninfected cells

Differential modulation of immune response and cytokine profiles in the bursae and spleen of chickens infected with very virulent infectious bursal disease virus

Background: Very virulent infectious bursal disease virus (vvIBDV) induces immunosuppression and inflammation in young birds, which subsequently leads to high mortality. In addition, infectious bursal disease (IBD) is one of the leading causes of vaccine failure on farms. Therefore, understanding the immunopathogenesis of IBDV in both the spleen and the bursae could help effective vaccine development. However, previous studies only profiled the differential expression of a limited number of cytokines, in either the spleen or the bursae of Fabricius of IBDV-infected chickens. Thus, this study aims to evaluate the in vitro and in vivo immunoregulatory effects of vvIBDV infection on macrophage-like cells, spleen and bursae of Fabricius. Results: The viral load was increased during the progression of the in vitro infection in the HD11 macrophage cell line and in vivo, but no significant difference was observed between the spleen and the bursae tissue. vvIBDV infection induced the expression of pro-inflammatory and Th1 cytokines, and chemokines from HD11 cells in a time- and dosage-dependent manner. Furthermore, alterations in the lymphocyte populations, cytokine and chemokine expression, were observed in the vvIBDV-infected spleens and bursae. A drastic rise was detected in numbers of macrophages and pro-inflammatory cytokine expression in the spleen, as early as 2 days post-infection (dpi). On 4 dpi, macrophage and T lymphocyte infiltration, associated with the peak expression of pro-inflammatory cytokines in the bursae tissues of infected chickens were observed. The majority of the significantly regulated pro-inflammatory cytokines and chemokines, in vvIBDV-infected spleens and bursae, were also detected in vvIBDV-infected HD11 cells. This cellular infiltration subsequently resulted in a sharp rise in nitric oxide (NO) and lipid peroxidation levels. Conclusion: This study suggests that macrophage may play an important role in regulating the early expression of pro-inflammatory cytokines, first in the spleen and then in the bursae, the latter tissue undergoing macrophage infiltration at 4 dpi