Preventive medicine: A cure for the healthcare crisis

Introductory Editorial: Few would dispute the premise that prevention, early detection, and early intervention form the first line of defense on the disease management (DM) continuum. That being the case, our national statistics on preventive health should be raising concerns throughout the industry. The US healthcare delivery system continues to fall woefully short of its prevention targets. On the international scene, the United States lags behind countries with less wealth and less technological savvy. Commentaries abound on the problems, but recently I became aware of an organization with an exciting goal and a novel solution for bringing preventive medicine into the mainstream. U.S. Preventive Medicine, Inc. (USPM) was founded by Christopher Fey, a former president and CEO of HealthCare USA, a multistate health maintenance organization, and senior officer of Coventry Health Care Corporation. A number of years ago, Mr. Fey had a life-altering experience. He witnessed his brother-in-law, a 39-year-old man in seemingly excellent physical condition, suffer a massive stroke that resulted in permanent right-sided paralysis, and speech and memory impairment. Following the event, physicians concluded that his brother-in-law’s risk factors could have been identified and his disease state detected by means of available technological screening devices. His was a condition for which effective drug therapy and other interventions were available. This event and its consequences were preventable. Having experienced firsthand the devastating consequences of a broken system that fails to respond until a condition produces symptoms, Mr. Fey became an evangelist for prevention and early detection. In founding USPM, he translated an interesting concept into an innovative model for preventive health in a consumer-driven market. In the following pages we provide a brief history of and current status report on the state of preventive health in the United States, and we present an overview of this company’s solution as one example of the untapped potential for innovation in the delivery of preventive services. I hope that the information contained herein will inspire you and our colleagues to join the conversation about the direction the United States will take with regard to improving access to screening and preventive services and enriching the lives of all citizens. As always, I welcome your comments. I can be reached at [email protected]

Panel. Faulkner and the Literary Canon

Considering the Unthinkable: The Risks and Rewards of Decanonizing Faulkner / Deborah Clarke, Arizona State UniversityAre we doing Faulkner any favors by canonizing him? To what extent does our belief in his greatness foreclose different ways of reading his work? Do we default to “if Faulkner did it, it must be brilliant,” giving him the benefit of all doubts? I’ll be looking at how our reverence for his work may actually hinder our understanding of it, as well as alienating students and colleagues who don’t dare to admit their resistance and doubt. Rather than using Faulkner’s difficulty as a way to silence critics, let’s consider what happens if we admit that it may be a problem. It’s time to re-think why Faulkner should—or shouldn’t—retain his position atop the American literary canon. Popular Faulkner: Pulp Paperbacks, Oprah’s Book Club, and the Curse of the Hypercanonical / Jaime Harker, University of MississippiBecause of Faulkner’s hypercanonical status—that is, because his writing seems to exemplify the autonomous aesthetic object, placed in opposition to mass culture—decades of brilliant scholarship about Faulkner’s deep and complicated relationship to popular culture have had little effect on the larger direction of Faulkner studies. Building on David Earle’s book Re-Covering Modernism, I suggest that Cold War paperbacks created an egalitarian, diverse reading and writing community that Oprah’s Book Club continued. I conclude by speculating about how a pulp Faulkner canon might construct a new vocabulary for talking about style that articulates multiple interpretive communities and their contingencies of value (in Barbara Herrnstein Smith’s provocative phrase). What happens when we no longer understand popular culture as base source material transformed by genius but as alternate interpretive communities? What if we consider a ‘fertile interchange’ without assuming that our own designations of quality are natural and innate? Benjy Compson\u27s Mind of the South / Mab Segrest, Connecticut CollegeBenjy Compson is more than likely the referent of Faulkner\u27s title for The Sound and the Fury. But a reading of the novel through the lens of southern psychiatric history and my own study of Georgia\u27s mammoth and iconic \u27lunatic asylum\u27\u27/sanitarium/state hospital at Milledgeville reveals the complex signification that results from the family\u27s decision to keep a cognitively disabled son and brother out of the state hospital. What do we learn about Faulkner and about the disciplining of mind in the Jim Crow South from Faulkner\u27s radical decision to write the novel\u27s opening from Benjy\u27s point of view? How do the Compsons’ choices and those of the African Americans who care for them and for Benjy reverberate through The Sound and the Fury and through other southern works, from To Kill a Mockingbird to The Violent Bear It Away to The Member of the Wedding to Streetcar Named Desire

Next generation software environments : principles, problems, and research directions

The past decade has seen a burgeoning of research and development in software environments. Conferences have been devoted to the topic of practical environments, journal papers produced, and commercial systems sold. Given all the activity, one might expect a great deal of consensus on issues, approaches, and techniques. This is not the case, however. Indeed, the term "environment" is still used in a variety of conflicting ways. Nevertheless substantial progress has been made and we are at least nearing consensus on many critical issues.The purpose of this paper is to characterize environments, describe several important principles that have emerged in the last decade or so, note current open problems, and describe some approaches to these problems, with particular emphasis on the activities of one large-scale research program, the Arcadia project. Consideration is also given to two related topics: empirical evaluation and technology transition. That is, how can environments and their constituents be evaluated, and how can new developments be moved effectively into the production sector

The Trans-Pacific Partnership Agreement: Looking Ahead to the Next Steps

Pressure has been building for the conclusion of the 12-country Trans-Pacific Partnership (TPP) negotiations. Getting the deal done is important, but the TPP is not just another free trade agreement (FTA). It represents the chance to set a trade agenda for the future across a wide range of topics for countries throughout the Asia-Pacific region. This means that the agreement should not be settled in haste. More importantly, it also means that key decisions need to be reached about broader issues related to the institutional structure of the TPP. These decisions must be made now, before the deal is closed, on issues such as how to create the TPP as a living agreement, the formation of a TPP Secretariat, and the clarification of entry conditions for future members such as the People’s Republic of China (PRC). These choices must be made deliberately and carefully even while officials are struggling with reaching closure on the most highly sensitive issues still remaining in the agreement. It will not be easy, but wise decisions are necessary now to ensure the long-term success of the TPP

The Australian Breast Cancer Tissue Bank (ABCTB)

The ABCTB was established in 2006 as an open access, not for profit resource dedicated to providing biospecimens and/or data to both national and international research projects in the field of breast cancer. Donors are consented according to standard ethical principles for use of their material for unspecified future research. ABCTB collects fully annotated clinical samples and associated clinical and longitudinal data from donors. Material and data is supplied to research projects.</p

Artificial intelligence in digital pathology: a diagnostic test accuracy systematic review and meta-analysis

Ensuring diagnostic performance of AI models before clinical use is key to the safe and successful adoption of these technologies. Studies reporting AI applied to digital pathology images for diagnostic purposes have rapidly increased in number in recent years. The aim of this work is to provide an overview of the diagnostic accuracy of AI in digital pathology images from all areas of pathology. This systematic review and meta-analysis included diagnostic accuracy studies using any type of artificial intelligence applied to whole slide images (WSIs) in any disease type. The reference standard was diagnosis through histopathological assessment and / or immunohistochemistry. Searches were conducted in PubMed, EMBASE and CENTRAL in June 2022. We identified 2976 studies, of which 100 were included in the review and 48 in the full meta-analysis. Risk of bias and concerns of applicability were assessed using the QUADAS-2 tool. Data extraction was conducted by two investigators and meta-analysis was performed using a bivariate random effects model. 100 studies were identified for inclusion, equating to over 152,000 whole slide images (WSIs) and representing many disease types. Of these, 48 studies were included in the meta-analysis. These studies reported a mean sensitivity of 96.3% (CI 94.1-97.7) and mean specificity of 93.3% (CI 90.5-95.4) for AI. There was substantial heterogeneity in study design and all 100 studies identified for inclusion had at least one area at high or unclear risk of bias. This review provides a broad overview of AI performance across applications in whole slide imaging. However, there is huge variability in study design and available performance data, with details around the conduct of the study and make up of the datasets frequently missing. Overall, AI offers good accuracy when applied to WSIs but requires more rigorous evaluation of its performance.Comment: 26 pages, 5 figures, 8 tables + Supplementary material

Long Non-coding RNAs Are Central Regulators of the IL-1β-Induced Inflammatory Response in Normal and Idiopathic Pulmonary Lung Fibroblasts

<p>There is accumulating evidence to indicate that long non-coding RNAs (lncRNAs) are important regulators of the inflammatory response. In this report, we have employed next generation sequencing to identify 14 lncRNAs that are differentially expressed in human lung fibroblasts following the induction of inflammation using interleukin-1β (IL-1β). Knockdown of the two most highly expressed lncRNAs, IL7AS, and MIR3142HG, showed that IL7AS negatively regulated IL-6 release whilst MIR3142HG was a positive regulator of IL-8 and CCL2 release. Parallel studies in fibroblasts derived from patients with idiopathic pulmonary fibrosis showed similar increases in IL7AS levels, that also negatively regulate IL-6 release. In contrast, IL-1β-induced MIR3142HG expression, and its metabolism to miR-146a, was reduced by 4- and 9-fold in IPF fibroblasts, respectively. This correlated with a reduced expression of inflammatory mediators whilst MIR3142HG knockdown showed no effect upon IL-8 and CCL2 release. Pharmacological studies showed that IL-1β-induced IL7AS and MIR3142HG production and release of IL-6, IL-8, and CCL2 in both control and IPF fibroblasts were mediated via an NF-κB-mediated pathway. In summary, we have cataloged those lncRNAs that are differentially expressed following IL-1β-activation of human lung fibroblasts, shown that IL7AS and MIR3142HG regulate the inflammatory response and demonstrated that the reduced inflammatory response in IPF fibroblast is correlated with attenuated expression of MIR3142HG/miR-146a.</p

Natural Variation in Interleukin-2 Sensitivity Influences Regulatory T-Cell Frequency and Function in Individuals With Long-standing Type 1 Diabetes.

Defective immune homeostasis in the balance between FOXP3+ regulatory T cells (Tregs) and effector T cells is a likely contributing factor in the loss of self-tolerance observed in type 1 diabetes (T1D). Given the importance of interleukin-2 (IL-2) signaling in the generation and function of Tregs, observations that polymorphisms in genes in the IL-2 pathway associate with T1D and that some individuals with T1D exhibit reduced IL-2 signaling indicate that impairment of this pathway may play a role in Treg dysfunction and the pathogenesis of T1D. Here, we have examined IL-2 sensitivity in CD4+ T-cell subsets in 70 individuals with long-standing T1D, allowing us to investigate the effect of low IL-2 sensitivity on Treg frequency and function. IL-2 responsiveness, measured by STAT5a phosphorylation, was a very stable phenotype within individuals but exhibited considerable interindividual variation and was influenced by T1D-associated PTPN2 gene polymorphisms. Tregs from individuals with lower IL-2 signaling were reduced in frequency, were less able to maintain expression of FOXP3 under limiting concentrations of IL-2, and displayed reduced suppressor function. These results suggest that reduced IL-2 signaling may be used to identify patients with the highest Treg dysfunction and who may benefit most from IL-2 immunotherapy.This work was supported by the JDRF UK Centre for Diabetes Genes, Autoimmunity and Prevention (D-GAP; 4-2007-1003), the Wellcome Trust (WT061858/091157) and the NIHR Cambridge Biomedical Research Centre (CBRC). The Cambridge Institute for Medical Research (CIMR) is in receipt of a Wellcome Trust Strategic Award (100140).This is the author accepted manuscript. The final version is available from the American Diabetes Association via http://dx.doi.org/10.2337/db15-051

Diversity and abundance of pteropods and heteropods along a latitudinal gradient across the Atlantic Ocean

AbstractShelled pteropods and heteropods are two independent groups of holoplanktonic gastropods that are potentially good indicators of the effects of ocean acidification. Although insight into their ecology and biogeography is important for predicting species-specific sensitivities to ocean change, the species abundances and biogeographical distributions of pteropods and heteropods are still poorly known. Here, we examined abundance and distribution patterns of pteropods (euthecosomes, pseudothecosomes, gymnosomes) and heteropods at 31 stations along a transect from 46°N to 46°S across the open waters of the Atlantic Ocean (Atlantic Meridional Transect cruise AMT24). We collected a total of 7312 pteropod specimens belonging to at least 31 species. Pteropod abundances were low north of 40°N with <15 individuals per 1000m3, varied between 100 and 2000ind./1000m3 between 30°N and 40°S, and reached >4000ind./1000m3 just south of 40°S. This accounted for an estimated biomass of 3.2mgm−3 south of 40°S and an average of 0.49mgm−3 along the entire transect. Species richness of pteropods was highest in the stratified (sub)tropical waters between 30°N and 30°S, with a maximum of 15 species per station. The biogeographical distribution of pteropod assemblages inferred by cluster analysis was largely congruent with the distribution of Longhurst’s biogeochemical provinces. Some pteropod species distributions were limited to particular oceanographic provinces, for example, subtropical gyres (e.g. Styliola subula) or warm equatorial waters (e.g. Creseis virgula). Other species showed much broader distributions between ∼35°N and ∼35°S (e.g. Limacina bulimoides and Heliconoides inflatus). We collected 1812 heteropod specimens belonging to 18 species. Highest heteropod abundances and species richness were found between 30°N and 20°S, with up to ∼700ind./1000m3 and a maximum of 14 species per station. Heteropods were not restricted to tropical and subtropical waters, however, as some taxa were also relatively abundant in subantarctic waters. Given the variation in distribution patterns among pteropod and heteropod species, it is likely that species will differ in their response to ocean changes