Greater TTIP Ambition in Chemicals: Why and how. CEPS Special Report, 28 July 2015. Paper No. 10 in the CEPS-CTR project ‘TTIP in the Balance’ and CEPS Special Report No. 114/July 2015.

To date, the negotiations over chemicals in the Translatlantic Trade and Investment Partnership (TTIP) have not shown sufficient ambition. The talks have focused too much on the differences in the two ‘systems’, rather than on the actual levels of health and environmental protection for substances regulated by both the US and the EU. Given the accomplishments within the OECD and the UN Globally Harmonised System of Classification and Labelling of Chemicals (GHS), the question is whether TTIP can be any more ambitious in the area of chemicals? We find that there is no detailed or systematic knowledge about how the two levels of protection in chemicals compare, although caricatures and stereotypes abound. This is partly due to an obsessive focus on a single US federal law, the Toxic Subtances Control Act (TSCA), whereas in practice US protection depends on many statutes and regulations, as well as on voluntary withdrawals (under pressure from the Environmental Protection Agency) and severe common law liability. This paper makes the economic case for firmly addressing the regulatory barriers, discusses the EU’s proposals, finds that the European Parliament’s Resolution on TTIP of July 2015 lacks a rationale (for chemicals), argues that both TSCA and REACH ought to be improved (based on ‘better regulation’), discusses the link with a global regime, advocates significant improvement of market access where equivalence of health and environmental objectives is agreed and, finally, proposes to lower the costs for companies selling in both markets by allowing them to opt into the other party’s more stringent rules, thereby avoiding duplication while racing-to-the-top. The ‘living agreement’ on chemicals ought to be led by a new TTIP institution authorised to establish the level of health and environmental protection on both sides of the Atlantic for substances regulated on both sides. These findings will lay the foundation for a highly beneficial lowering of trading costs without in any way affecting the level of protection. Indeed, this is exactly what TTIP is, or should be, all about.This paper is the 10th in a series produced in the context of the “TTIP in the Balance” project, jointly organised by CEPS and the Center for Transatlantic Relations (CTR) in Washington, D.C. It is published simultaneously on the CEPS (www.ceps.eu) and CTR websites (http://transatlantic.sais-jhu.edu)

Point mutations in the α2 domain of HLA-A2.1 define a functionally relevant interaction with TAP

AbstractBackground: Glycoproteins encoded by the major histocompatibility complex class I region (MHC class I) present peptide antigens to cytotoxic T cells (CTLs). Peptides are delivered to the site of MHC class I assembly by the transporter associated with antigen processing (TAP), and cell lines that lack this transporter are unable to present endogenous antigens to CTLs. Although it has been shown that a fraction of newly synthesized class I molecules are in physical association with TAP, it is not known whether this interaction is functionally relevant, or where on the class I molecule the TAP binding site might be.Results C1R cells transfected with a mutant HLA-A2.1 heavy chain (HC), where threonine at position 134 in the α2 domain is changed to lysine (T134K), are unable to present endogenous antigens to CTLs. We have studied the biochemistry of this mutant in C1R cells, and found that a large pool of unstable empty class I HC–β2m (β-2 microglobulin) heterodimers exist that are rapidly transported to the cell surface. The T134K mutant seemed to bind peptide antigens and assemble with β2m as efficiently as wild-type HLA-A2.1. However, we show here that the inefficiency with which T134K presents intracellular antigen is associated with its inability to interact with the TAP heterodimer.Conclusion These experiments establish that the class I–TAP interaction is obligatory for the presentation of peptide epitopes delivered to the endoplasmic reticulum (ER) by TAP. Wild-type HLA-A2.1 molecules in TAP-deficient cells are retained in the ER, whereas T134K is rapidly released to the cell surface, but is unstable, suggesting a role for the TAP complex as an intracellular checkpoint that only affects the release of class I molecules with stably bound peptide ligands

Early History of Mammals Is Elucidated with the ENCODE Multiple Species Sequencing Data

Understanding the early evolution of placental mammals is one of the most challenging issues in mammalian phylogeny. Here, we addressed this question by using the sequence data of the ENCODE consortium, which include 1% of mammalian genomes in 18 species belonging to all main mammalian lineages. Phylogenetic reconstructions based on an unprecedented amount of coding sequences taken from 218 genes resulted in a highly supported tree placing the root of Placentalia between Afrotheria and Exafroplacentalia (Afrotheria hypothesis). This topology was validated by the phylogenetic analysis of a new class of genomic phylogenetic markers, the conserved noncoding sequences. Applying the tests of alternative topologies on the coding sequence dataset resulted in the rejection of the Atlantogenata hypothesis (Xenarthra grouping with Afrotheria), while this test rejected the second alternative scenario, the Epitheria hypothesis (Xenarthra at the base), when using the noncoding sequence dataset. Thus, the two datasets support the Afrotheria hypothesis; however, none can reject both of the remaining topological alternatives

Substantial reductions in the number of diabetic ketoacidosis and severe hypoglycaemia episodes requiring emergency treatment lead to reduced costs after structured education in adults with Type 1 diabetes

Aims To determine the impact of structured education promoting flexible intensive insulin therapy on rates of diabetic ketoacidosis, and the costs associated with emergency treatment for severe hypoglycaemia and ketoacidosis in adults with Type 1 diabetes. Methods Using the Dose Adjustment For Normal Eating research database we compared the rates of ketoacidosis and severe hypoglycaemia during the 12 months preceding Dose Adjustment For Normal Eating training with the rates during the 12-month follow-up after this training. Emergency treatment costs were calculated for associated paramedic assistance, Accident and Emergency department attendance and hospital admissions. Results Complete baseline and 1-year data were available for 939/1651 participants (57%). The risk of ketoacidosis in the 12 months after Dose Adjustment For Normal Eating training, compared with that before training, was 0.39 (95% CI: 0.23 to 0.65, P < 0.001), reduced from 0.07 to 0.03 episodes/patient/year. For every 1 mmol/mol unit increase in HbA1c concentration, the risk of a ketoacidosis episode increased by 6% (95% CI: 5 to 7%; 88% for a 1% increase), and for each 5-year increase in diabetes duration, the relative risk reduced by 20% (95% CI: 19 to 22%). The number of emergency treatments decreased for ketoacidosis (P < 0.001), and also for severe hypoglycaemia, including paramedic assistance (P < 0.001), Accident and Emergency department attendance (P = 0.029) and hospital admission (P = 0.001). In the study cohort, the combined cost of emergency treatment for ketoacidosis and severe hypoglycaemia fell by 64%, from £119,470 to £42,948. Conclusions Structured training in flexible intensive insulin therapy is associated with a 61% reduction in the risk of ketoacidosis and with 64% lower emergency treatment costs for ketoacidosis and severe hypoglycaemia

Nocardia farcinica lung infection in a patient with cystic fibrosis: a case report

<p>Abstract</p> <p>Introduction</p> <p>Respiratory tract infections are the major causes of morbidity and mortality in patients with cystic fibrosis. <it>Nocardia </it>are rarely implicated in these infections and few reports of the involvement of this species are found in the literature.</p> <p>Case presentation</p> <p>We describe a case of lung infection followed by chronic colonization of trimethoprim and sulfamethoxazole resistant <it>Nocardia farcinica </it>in a patient with cystic fibrosis. The chronic colonization of this uncommon bacterium in patients with cystic fibrosis was proved using a newly developed real-time polymerase chain reaction assay, which indicates that this bacterium, despite treatment, is difficult to eradicate.</p> <p>Conclusion</p> <p>Our case report confirms that this organism can be recovered in persons with cystic fibrosis. Its eradication is necessary especially if the patient is to undergo lung transplantation.</p

Rule-Makers or Rule-Takers? Exploring the Transatlantic Trade and Investment Partnership

The Transatlantic Trade and Investment Partnership (TTIP) is an effort by the United States and the European Union to reposition themselves for a world of diffuse economic power and intensified global competition. It is a next-generation economic negotiation that breaks the mould of traditional trade agreements. At the heart of the ongoing talks is the question whether and in which areas the two major democratic actors in the global economy can address costly frictions generated by their deep commercial integration by aligning rules and other instruments. The aim is to reduce duplication in various ways in areas where levels of regulatory protection are equivalent as well as to foster wide-ranging regulatory cooperation and set a benchmark for high-quality global norms. In this volume, European and American experts explain the economic context of TTIP and its geopolitical implications, and then explore the challenges and consequences of US-EU negotiations across numerous sensitive areas, ranging from food safety and public procurement to economic and regulatory assessments of technical barriers to trade, automotive, chemicals, energy, services, investor-state dispute settlement mechanisms and regulatory cooperation. Their insights cut through the confusion and tremendous public controversies now swirling around TTIP, and help decision-makers understand how the United States and the European Union can remain rule-makers rather than rule-takers in a globalising world in which their relative influence is waning

Symmetry-breaking in the endofullerene H2O@C60 revealed in the quantum dynamics of ortho and para-water: a neutron scattering investigation

Inelastic neutron scattering (INS) has been employed to investigate the quantum dynamics of water molecules permanently entrapped inside the cages of C60 fullerene molecules. This study of the supramolecular complex, H2O@C60, provides the unique opportunity to study isolated water molecules in a highly symmetric environment. Free from strong interactions, the water molecule has a high degree of rotational freedom enabling its nuclear spin isomers, ortho-H2O and para-H2O to be separately identified and studied. The INS technique mediates transitions between the ortho and para spin isomers and using three INS spectrometers, the rotational levels of H2O have been investigated, correlating well with the known levels in gaseous water. The slow process of nuclear spin conversion between ortho-H2O and para-H2O is revealed in the time dependence of the INS peak intensities over periods of many hours. Of particular interest to this study is the observed splitting of the ground state of ortho-H2O, raising the three-fold degeneracy into two states with degeneracy 2 and 1 respectively. This is attributed to a symmetry-breaking interaction of the water environment