Issue Framing as a Tool to Understand Opportunities for Policy Change

The global climate change agreement completed on December 12, 2015 in Paris set a collective target to cap greenhouse gas emissions in order to limit the temperature increase to 2 degrees Celsius with a goal to get as close as possible to 1.5 degrees above pre-industrial levels. These goals were to be accomplished through a “bottom up” mechanism for national policy approaches in which states made their own choices about how they would meet climate targets. This paper examines why and how an agreement was possible in 2015 when it had not been before. What was different in Paris, or leading up to Paris, so that the parties involved successfully came to an agreement when it was not possible in Copenhagen? This paper presents a problem definition and issue framing perspective to examine the shift in the discussion in Paris from the burdens of climate action to opportunities climate action offered for economic and development models. It provides a road map to understand the role of key stakeholders, including governments, the business community, civil society, and subnational actors in the making of the climate agreement

Overcoming Obstacles in Global Climate Action from Copenhagen to Paris: Issue Framing as a Tool to Understand Opportunities for Policy Change

The global climate change agreement completed on December 12, 2015 in Paris set a collective target to cap greenhouse gas emissions in order to limit the temperature increase to 2 degrees Celsius with a goal to get as close as possible to 1.5 degrees above pre-industrial levels. These goals were to be accomplished through a “bottom up” mechanism for national policy approaches in which states made their own choices about how they would meet climate targets. This paper examines why and how an agreement was possible in 2015 when it had not been before. What was different in Paris, or leading up to Paris, so that the parties involved successfully came to an agreement when it was not possible in Copenhagen? This paper presents a problem definition and issue framing perspective to examine the shift in the discussion in Paris from the burdens of climate action to opportunities climate action offered for economic and development models. It provides a road map to understand the role of key stakeholders, including governments, the business community, civil society, and subnational actors in the making of the climate agreement

Students’ Perceptions about Successfully Transitioning to Postsecondary Institutions

Through the auspices of federal legislation, students with disabilities are gaining access to higher education. Still for many students with disabilities, the paramount barriers facing them in their transition to postsecondary education are overwhelming. This paper reports the findings of a qualitative study of 59 postsecondary students with disabilities on factors students perceived to inhibit or contribute to their successful transition into college. The study examines support services and access to reasonable accommodations available to students with disabilities. Students reported the major barriers to accessing college and succeeding in college were societal attitudes, lack of preparation, and financial constraints. The students also identified self-determination and families as necessary supports that propelled their transition into postsecondary education. Recommendations and suggestions for teachers, students, and families are presented by the study’s participants to support students’ with disabilities access and retention in postsecondary institutions

Nine years of comparative effectiveness research education and training: initiative supported by the PhRMA Foundation

The term comparative effectiveness research (CER) took center stage with passage of the American Recovery and Reinvestment Act (2009). The companion US$1.1 billion in funding prompted the launch of initiatives to train the scientific workforce capable of conducting and using CER. Passage of the Patient Protection and Affordable Care Act (2010) focused these initiatives on patients, coining the term ‘patient-centered outcomes research’ (PCOR). Educational and training initiatives were soon launched. This report describes the initiative of the Pharmaceutical Research and Manufacturers Association of America (PhRMA) Foundation. Through provision of grant funding to six academic Centers of Excellence, to spearheading and sponsoring three national conferences, the PhRMA Foundation has made significant contributions to creation of the scientific workforce that conducts and uses CER/PCOR

Systemic lupus erythematosus induced by anti-tumour necrosis factor alpha therapy: a French national survey

The development of drug-induced lupus remains a matter of concern in patients treated with anti-tumour necrosis factor (TNF) alpha. The incidence of such adverse effects is unknown. We undertook a retrospective national study to analyse such patients. Between June and October 2003, 866 rheumatology and internal medicine practitioners from all French hospital centres prescribing anti-TNF in rheumatic diseases registered on the website of the 'Club Rhumatismes et Inflammation' were contacted by email to obtain the files of patients with TNF-induced systemic lupus erythematosus. Twenty-two cases were collected, revealing two aspects of these manifestations. Ten patients (six patients receiving infliximab, four patients receiving etanercept) only had anti-DNA antibodies and skin manifestations one could classify as 'limited skin lupus' or 'toxidermia' in a context of autoimmunity, whereas 12 patients (nine patients receiving infliximab, three patients receiving etanercept) had more complete drug-induced lupus with systemic manifestations and at least four American Congress of Rheumatology criteria. One patient had central nervous system manifestations. No patients had lupus nephritis. The signs of lupus occurred within a mean of 9 months (range 3–16 months) in patients treated with infliximab and within a mean of 4 months (range 2–5 months) in patients treated with etanercept. In all cases after diagnosis was determined, anti-TNF was stopped and specific treatment introduced in eight patients: two patients received intravenous methylprednisolone, four patients received oral steroids (15–35 mg/day), and two patients received topical steroids. Lupus manifestations abated within a few weeks (median 8 weeks, standard deviation 3–16) in all patients except one with longer-lasting evolution (6 months). At that time, cautious estimations (unpublished data from Schering Plough Inc. and Wyeth Inc.) indicated that about 7700 patients had been exposed to infliximab and 3000 to etanercept for inflammatory arthritides in France. It thus appears that no drug was more implicated than the other in lupus syndromes, whose incidence was 15/7700 = 0.19% with infliximab and 7/3800 = 0.18% with etanercept. Clinicians should be aware that lupus syndromes with systemic manifestations may occur in patients under anti-TNF alpha treatment

Genotyping structural variants in pangenome graphs using the vg toolkit.

Structural variants (SVs) remain challenging to represent and study relative to point mutations despite their demonstrated importance. We show that variation graphs, as implemented in the vg toolkit, provide an effective means for leveraging SV catalogs for short-read SV genotyping experiments. We benchmark vg against state-of-the-art SV genotypers using three sequence-resolved SV catalogs generated by recent long-read sequencing studies. In addition, we use assemblies from 12 yeast strains to show that graphs constructed directly from aligned de novo assemblies improve genotyping compared to graphs built from intermediate SV catalogs in the VCF format

Mycolactone subverts immunity by selectively blocking the Sec61 translocon

Mycolactone, an immunosuppressive macrolide released by the human pathogen Mycobacterium ulcerans, was previously shown to impair Sec61-dependent protein translocation, but the underlying molecular mechanism was not identified. In this study, we show that mycolactone directly targets the alpha subunit of the Sec61 translocon to block the production of secreted and integral membrane proteins with high potency. We identify a single-amino acid mutation conferring resistance to mycolactone, which localizes its interaction site near the lumenal plug of Sec61 alpha. Quantitative proteomics reveals that during T cell activation, mycolactone-mediated Sec61 blockade affects a selective subset of secretory proteins including key signal-transmitting receptors and adhesion molecules. Expression of mutant Sec61 alpha in mycolactone-treated T cells rescued their homing potential and effector functions. Furthermore, when expressed in macrophages, the mycolactone-resistant mutant restored IFN-gamma receptor-mediated antimicrobial responses. Thus, our data provide definitive genetic evidence that Sec61 is the host receptor mediating the diverse immunomodulatory effects of mycolactone and identify Sec61 as a novel regulator of immune cell functions.Peer reviewe

The case for strategic international alliances to harness nutritional genomics for public and personal health

Nutrigenomics is the study of how constituents of the diet interact with genes, and their products, to alter phenotype and, conversely, how genes and their products metabolise these constituents into nutrients, antinutrients, and bioactive compounds. Results from molecular and genetic epidemiological studies indicate that dietary unbalance can alter gene-nutrient interactions in ways that increase the risk of developing chronic disease. The interplay of human genetic variation and environmental factors will make identifying causative genes and nutrients a formidable, but not intractable, challenge. We provide specific recommendations for how to best meet this challenge and discuss the need for new methodologies and the use of comprehensive analyses of nutrient-genotype interactions involving large and diverse populations. The objective of the present paper is to stimulate discourse and collaboration among nutrigenomic researchers and stakeholders, a process that will lead to an increase in global health and wellness by reducing health disparities in developed and developing countrie