Glocal Pharma

The Open Access version of this book, available at http://www.tandfebooks.com, has been made available under a Creative Commons Attribution-Non Commercial-No Derivatives 3.0 license. An exploration of how global pharmaceutical products are localized - of what happens when they become ‘glocal’ - this book examines the tensions that exist between a global pharmaceutical market and the locally bounded discourses and regulations encountered as markets are created for new drugs in particular contexts. Employing the case study of the emergence, representation and regulation of Viagra in the Swedish market, Glocal Pharma offers analyses of commercial material, medical discourses and legal documents to show how a Swedish, Viagra-consuming subject has been constructed in relation to the drug and how Viagra is imagined in relation to the Swedish man. Engaging with debates about pharmaceuticalization, the authors consider the ways in which new identities are created around drugs, the redefinition of health problems as sites of pharmaceutical treatment and changes in practices of governance to reflect the entrance of pharmaceuticals to the market. With attention to ‘local’ contexts, it reveals elements in the nexus of pharmaceutcalization that are receptive to cultural elements as new products become embedded in local markets. An empirically informed study of the the ways in which the presence of a drug can alter the concept of a disease and its treatment, understandings of who suffers from it and how to cure it - both locally and internationally - this book will appeal to scholars of sociology and science and technology studies with interests in globalization, pharmaceuticals, gender and the sociology of medicine

Three-Component Glycolate Michael Reactions of Enolates, Silyl Glyoxylates, and α,β-Enones

Silyl glyoxylates react with enolates and enones to afford either glycolate aldol or Michael adducts. Product identity is controlled by the countercation associated with the enolate. Reformatsky nucleophiles in the presence of additional Zn(OTf)2 result in aldol coupling (A), while lithium enolates provide the Michael coupling (B). Deprotonation of the aldol product A with LDA induces equilibration to form the minor diastereomer of Michael product B. This observation suggests that formation of the major diastereomer of Michael product B does not occur via an aldol/retro-aldol/Michael sequence

Glocal Pharma

The Open Access version of this book, available at http://www.tandfebooks.com, has been made available under a Creative Commons Attribution-Non Commercial-No Derivatives 3.0 license. An exploration of how global pharmaceutical products are localized - of what happens when they become ‘glocal’ - this book examines the tensions that exist between a global pharmaceutical market and the locally bounded discourses and regulations encountered as markets are created for new drugs in particular contexts. Employing the case study of the emergence, representation and regulation of Viagra in the Swedish market, Glocal Pharma offers analyses of commercial material, medical discourses and legal documents to show how a Swedish, Viagra-consuming subject has been constructed in relation to the drug and how Viagra is imagined in relation to the Swedish man. Engaging with debates about pharmaceuticalization, the authors consider the ways in which new identities are created around drugs, the redefinition of health problems as sites of pharmaceutical treatment and changes in practices of governance to reflect the entrance of pharmaceuticals to the market. With attention to ‘local’ contexts, it reveals elements in the nexus of pharmaceutcalization that are receptive to cultural elements as new products become embedded in local markets. An empirically informed study of the the ways in which the presence of a drug can alter the concept of a disease and its treatment, understandings of who suffers from it and how to cure it - both locally and internationally - this book will appeal to scholars of sociology and science and technology studies with interests in globalization, pharmaceuticals, gender and the sociology of medicine

Relationships between sexual violence and chronic disease: a cross-sectional study

A grant from the One-University Open Access Fund at the University of Kansas was used to defray the author’s publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.Background: Sexual assault is a traumatic event with potentially devastating lifelong effects on physical and mental health. Research has demonstrated that individuals who experience sexual assault during childhood are more likely to engage in risky behaviors later in life, such as smoking, alcohol and drug use, and disordered eating habits, which may increase the risk of developing a chronic disease. Despite the high prevalence and economic burden of sexual assault, few studies have investigated the associations between sexual violence and chronic health conditions in the US. The purpose of this study is to identify associations between sexual violence and health risk behaviors, chronic health conditions and mental health conditions utilizing population based data in Kansas. Methods: Secondary analysis was done using data from the 2011 Kansas Behavioral Risk Factor Surveillance System sexual violence module (N = 4,886). Crude and adjusted prevalence rate ratios were computed to examine associations between sexual assault and health risk behaviors, chronic health conditions and mental health conditions, overall and after adjusting for social demographic characteristics. Additional logistic regression models were implemented to examine the association between sexual assault and health risk behaviors with further adjustment for history of anxiety or depression. Results: There was a significantly higher prevalence of health risk behaviors (heavy drinking, binge drinking and current smoking), chronic health conditions (disability, and current asthma) and mental health conditions (depression, anxiety, and suicidal ideation) among women who ever experienced sexual assault compared to women who did not, even after adjustment for potential confounders. Conclusions: Study findings highlight the need for chronic disease prevention services for victims of sexual violence. There are important implications for policies and practices related to primary, secondary, and tertiary prevention, as well as collaborations between sexual violence, chronic disease, and health risk behavior programs

α-Amination of keto-nitrones via Multihetero-Cope rearrangement employing an imidoyl chloride reagent

α-Aminations of ketone-derived nitrones have been developed via [3,3]-rearrangement of the intermediates generated upon condensation with imidoyl chlorides. Careful reagent selection provides synthetically attractive amino protecting groups. The enediamide or α′-carbamoyl enamide products can be hydrolyzed to the desired carbonyl, or exposed to electrophiles for further α-functionalization

Muscular adaptations in drop set vs. traditional training: a meta-analysis

The purpose of this paper was to systematically review and meta-analyze the effects of drop set training (DS) vs. traditional training (TRAD) on measures of muscle strength and hypertrophy. We carried out a comprehensive search on PubMed/MEDLINE, Scopus, Web of Science, and CINAHL databases for studies that satisfied the following criteria: (a) had a randomized experimental design (either within- or between-group); (b) directly compared DS versus TRAD; (c) assessed changes in muscular strength and/or hypertrophy; (d) had a training protocol that lasted a minimum of 6 weeks, and; (e) involved apparently healthy participants. We employed a robust variance meta-analysis model, with adjustments for small samples. Study quality was assessed by the Downs and Black checklist. A total of 5 studies met inclusion criteria. Qualitative assessment indicated the included studies were of moderate to good quality. For the strength outcomes results indicated a trivial point estimate of the effect size (ES) with a relatively narrow precision for the confidence interval (CI) estimate (0.07; 95% CI = -0.14, 0.29). Similarly, results for the hypertrophy outcomes indicated a trivial point estimate of the ES with a relatively narrow precision for the CI estimate (0.08; 95% CI = -0.08, 0.24). In conclusion, DS and TRAD appear to have similar effects on muscular strength and hypertrophy. This would seem to indicate that both DS and TRAD are viable options for promoting muscular adaptations; DS may provide a more time-efficient alternative for achieving results

The accessible chromatin landscape of the human genome

DNaseI hypersensitive sites (DHSs) are markers of regulatory DNA and have underpinned the discovery of all classes of cis-regulatory elements including enhancers, promoters, insulators, silencers, and locus control regions. Here we present the first extensive map of human DHSs identified through genome-wide profiling in 125 diverse cell and tissue types. We identify ~2.9 million DHSs that encompass virtually all known experimentally-validated cis-regulatory sequences and expose a vast trove of novel elements, most with highly cell-selective regulation. Annotating these elements using ENCODE data reveals novel relationships between chromatin accessibility, transcription, DNA methylation, and regulatory factor occupancy patterns. We connect ~580,000 distal DHSs with their target promoters, revealing systematic pairing of different classes of distal DHSs and specific promoter types. Patterning of chromatin accessibility at many regulatory regions is choreographed with dozens to hundreds of co-activated elements, and the trans-cellular DNaseI sensitivity pattern at a given region can predict cell type-specific functional behaviors. The DHS landscape shows signatures of recent functional evolutionary constraint. However, the DHS compartment in pluripotent and immortalized cells exhibits higher mutation rates than that in highly differentiated cells, exposing an unexpected link between chromatin accessibility, proliferative potential and patterns of human variation

Consensus-based care recommendations for adults with myotonic dystrophy type 1

Purpose of review Myotonic dystrophy type 1 (DM1) is a severe, progressive genetic disease that affects between 1 in 3,000 and 8,000 individuals globally. No evidence-based guideline exists to inform the care of these patients, and most do not have access to multidisciplinary care centers staffed by experienced professionals, creating a clinical care deficit. Recent findings The Myotonic Dystrophy Foundation (MDF) recruited 66 international clinicians experienced in DM1 patient care to develop consensus-based care recommendations. MDF created a 2-step methodology for the project using elements of the Single Text Procedure and the Nominal Group Technique. The process generated a 4-page Quick Reference Guide and a comprehensive, 55-page document that provides clinical care recommendations for 19 discrete body systems and/or care considerations. Summary The resulting recommendations are intended to help standardize and elevate care for this patient population and reduce variability in clinical trial and study environments. Described as “one of the more variable diseases found in medicine,” myotonic dystrophy type 1 (DM1) is an autosomal dominant, triplet-repeat expansion disorder that affects somewhere between 1:3,000 and 1:8,000 individuals worldwide.1 There is a modest association between increased repeat expansion and disease severity, as evidenced by the average age of onset and overall morbidity of the condition. An expansion of over 35 repeats typically indicates an unstable and expanding mutation. An expansion of 50 repeats or higher is consistent with a diagnosis of DM1. DM1 is a multisystem and heterogeneous disease characterized by distal weakness, atrophy, and myotonia, as well as symptoms in the heart, brain, gastrointestinal tract, endocrine, and respiratory systems. Symptoms may occur at any age. The severity of the condition varies widely among affected individuals, even among members of the same family. Comprehensive evidence-based guidelines do not currently exist to guide the treatment of DM1 patients. As a result, the international patient community reports varied levels of care and care quality, and difficulty accessing care adequate to manage their symptoms, unless they have access to multidisciplinary neuromuscular clinics. Consensus-based care recommendations can help standardize and improve the quality of care received by DM1 patients and assist clinicians who may not be familiar with the significant variability, range of symptoms, and severity of the disease. Care recommendations can also improve the landscape for clinical trial success by eliminating some of the inconsistencies in patient care to allow more accurate understanding of the benefit of potential therapies

The accessible chromatin landscape of the human genome

DNaseI hypersensitive sites (DHSs) are markers of regulatory DNA and have underpinned the discovery of all classes of cis-regulatory elements including enhancers, promoters, insulators, silencers, and locus control regions. Here we present the first extensive map of human DHSs identified through genome-wide profiling in 125 diverse cell and tissue types. We identify ~2.9 million DHSs that encompass virtually all known experimentally-validated cis-regulatory sequences and expose a vast trove of novel elements, most with highly cell-selective regulation. Annotating these elements using ENCODE data reveals novel relationships between chromatin accessibility, transcription, DNA methylation, and regulatory factor occupancy patterns. We connect ~580,000 distal DHSs with their target promoters, revealing systematic pairing of different classes of distal DHSs and specific promoter types. Patterning of chromatin accessibility at many regulatory regions is choreographed with dozens to hundreds of co-activated elements, and the trans-cellular DNaseI sensitivity pattern at a given region can predict cell type-specific functional behaviors. The DHS landscape shows signatures of recent functional evolutionary constraint. However, the DHS compartment in pluripotent and immortalized cells exhibits higher mutation rates than that in highly differentiated cells, exposing an unexpected link between chromatin accessibility, proliferative potential and patterns of human variation