Climate for Collaboration: Analysis of US and EU Lessons and Opportunities in Energy and Climate Policy

A deepening of cooperation between the United States and the European Union requires mutual trust, and understanding of current policies, challenges and successes. Through providing such understanding among policymakers, industry and other stakeholders in both economies, opportunities for transatlantic cooperation on climate change and energy policy emerge. This paper sets out by discussing the environmental, legislative, and economic contexts of the EU and US as related to climate. This context is essential to understanding how cap-and-trade, renewable energy and sustainable transportation policies have taken shape in the EU and the US, as described in Chapter 3.1. For each of these policies, a barrier analysis and discussion is provided. Chapter 4 builds off this improved understanding to listobservations and possible lessons learned. The paper concludes with recommendations on topics where EU and US interests align, and where further cooperation could prove beneficial

Efficacy of three neuroprotective drugs in secondary progressive multiple sclerosis (MS-SMART):a phase 2b, multiarm, double-blind, randomised placebo-controlled trial

Neurodegeneration is the pathological substrate that causes major disability in secondary progressive multiple sclerosis. A synthesis of preclinical and clinical research identified three neuroprotective drugs acting on different axonal pathobiologies. We aimed to test the efficacy of these drugs in an efficient manner with respect to time, cost, and patient resource. Methods: We did a phase 2b, multiarm, parallel group, double-blind, randomised placebo-controlled trial at 13 clinical neuroscience centres in the UK. We recruited patients (aged 25-65 years) with secondary progressive multiple sclerosis who were not on disease-modifying treatment and who had an Expanded Disability Status Scale (EDSS) score of 4·0-6·5. Participants were randomly assigned (1:1:1:1) at baseline, by a research nurse using a centralised web-based service, to receive twice-daily oral treatment of either amiloride 5 mg, fluoxetine 20 mg, riluzole 50 mg, or placebo for 96 weeks. The randomisation procedure included minimisation based on sex, age, EDSS score at randomisation, and trial site. Capsules were identical in appearance to achieve masking. Patients, investigators, and MRI readers were unaware of treatment allocation. The primary outcome measure was volumetric MRI percentage brain volume change (PBVC) from baseline to 96 weeks, analysed using multiple regression, adjusting for baseline normalised brain volume and minimisation criteria. The primary analysis was a complete-case analysis based on the intention-to-treat population (all patients with data at week 96). This trial is registered with ClinicalTrials.gov, NCT01910259

In vitro anti-HIV activity of some Indian medicinal plant extracts

Background Human Immunodeficiency Virus (HIV) persists to be a significant public health issue worldwide. The current strategy for the treatment of HIV infection, Highly Active Antiretroviral Therapy (HAART), has reduced deaths from AIDS related disease, but it can be an expensive regime for the underdeveloped and developing countries where the supply of drugs is scarce and often not well tolerated, especially in persons undergoing long term treatment. The present therapy also has limitations of development of multidrug resistance, thus there is a need for the discovery of novel anti-HIV compounds from plants as a potential alternative in combating HIV disease. Methods Ten Indian medicinal plants were tested for entry and replication inhibition against laboratory adapted strains HIV-1IIIB, HIV-1Ada5 and primary isolates HIV-1UG070, HIV-1VB59 in TZM-bl cell lines and primary isolates HIV-1UG070, HIV-1VB59 in PM1 cell lines. The plant extracts were further evaluated for toxicity in HEC-1A epithelial cell lines by transwell epithelial model. Results The methanolic extracts of Achyranthes aspera, Rosa centifolia and aqueous extract of Ficus benghalensis inhibited laboratory adapted HIV-1 strains (IC80 3.6–118 μg/ml) and primary isolates (IC80 4.8–156 μg/ml) in TZM-bl cells. Methanolic extract of Strychnos potatorum, aqueous extract of Ficus infectoria and hydroalcoholic extract of Annona squamosa inhibited laboratory adapted HIV-1 strains (IC80 4.24–125 μg/ml) and primary isolates (IC80 18–156 μg/ml) in TZM-bl cells. Methanolic extracts of Achyranthes aspera and Rosa centifolia, (IC801-9 μg/ml) further significantly inhibited HIV-1 primary isolates in PM1cells. Methanolic extracts of Tridax procumbens, Mallotus philippinensis, Annona reticulate, aqueous extract of Ficus benghalensis and hydroalcoholic extract of Albizzia lebbeck did not exhibit anti-HIV activity in all the tested strains. Methanolic extract of Rosa centifolia also demonstrated to be non-toxic to HEC-1A epithelial cells and maintained epithelial integrity (at 500 μg/ml) when tested in transwell dual-chamber. Conclusion These active methanolic extracts of Achyranthes aspera and Rosa centifolia, could be further subjected to chemical analysis to investigate the active moiety responsible for the anti-HIV activity. Methanolic extract of Rosa centifolia was found to be well tolerated maintaining the epithelial integrity of HEC-1A cells in vitro and thus has potential for investigating it further as candidate microbicide

GagCM9-Specific CD8+ T Cells Expressing Limited Public TCR Clonotypes Do Not Suppress SIV Replication In Vivo

Several lines of evidence suggest that HIV/SIV-specific CD8+ T cells play a critical role in the control of viral replication. Recently we observed high levels of viremia in Indian rhesus macaques vaccinated with a segment of SIVmac239 Gag (Gag45–269) that were subsequently infected with SIVsmE660. These seven Mamu-A*01+ animals developed CD8+ T cell responses against an immunodominant epitope in Gag, GagCM9, yet failed to control virus replication. We carried out a series of immunological and virological assays to understand why these Gag-specific CD8+ T cells could not control virus replication in vivo. GagCM9-specific CD8+ T cells from all of the animals were multifunctional and were found in the colonic mucosa. Additionally, GagCM9-specific CD8+ T cells accessed B cell follicles, the primary residence of SIV-infected cells in lymph nodes, with effector to target ratios between 20–250 GagCM9-specific CD8+ T cells per SIV-producing cell. Interestingly, vaccinated animals had few public TCR clonotypes within the GagCM9-specific CD8+ T cell population pre- and post-infection. The number of public TCR clonotypes expressed by GagCM9-specific CD8+ T cells post-infection significantly inversely correlated with chronic phase viral load. It is possible that these seven animals failed to control viral replication because of the narrow TCR repertoire expressed by the GagCM9-specific CD8+ T cell population elicited by vaccination and infection

Efeito de extratos orgânicos, associados ao surfactante tween 80, na germinação e crescimento de plântulas de alface Effect of organic extracts associated with surfactant Tween 80 on seed germination and seedling growth of lettuce

Com este trabalho, visou-se a identificar, por meio de bioensaio, o efeito dos extratos de caruru (Amaranthus retroflexus L.), capim-marmelada (Brachiaria plantaginea (Link.) Hitchc.), mentrasto (Ageratum conyzoides L.) e de três cultivares de milho (AG1051, C333 e C435) sobre a germinação e crescimento de alface (Lactuca sativa L. cv. Marisa AG216). Os extratos metanólicos foram concentrados sob vácuo e solubilizados em surfactante Tween 80 a 1% (v/v) em água. A seguir, aplicaram-se as soluções obtidas em papel de filtro sobre placa de Petri, onde foi semeada alface. Utilizaram-se água destilada como testemunha e surfactante Tween 80 a 1% como tratamento branco. O extrato de mentrasto, o de caruru e da cultivar de milho AG1051 promoveram redução no índice de velocidade de germinação em relação à testemunha com água destilada. O percentual de germinação foi afetado apenas pelo extrato de mentrasto (82,5% de redução). Todos os extratos e o surfactante Tween 80 provocaram inibição do crescimento de radículas de plântulas de alface, com redução de comprimento de raiz entre 9,53 e 14,83 mm, e de hipocótilo, entre 21,6 a 30,95 mm.<br>This work aimed at identifying, through bioassay, the effect of organic extracts of pigweed (Amaranthus retroflexus L.), signal grass (Brachiaria plantaginea (Link.) Hitchc.), ageratum (Ageratum conyzoides L.) and three corn cultivars (AG1051, C333 and C435) on lettuce (Lactuca sativa L. cv. Marisa AG216) germination and seedling. Thus, the methanolic extracts of their straws were concentrated under vacuum and dissolved in 1% (v/v) aqueous surfactant Tween 80. Then, the resulting solutions were applied to filter papers contained in Petri dishes, where lettuce was sowed. Distilled water and 1% Tween 80 were used as controls treatment. The corn cultivar extracts AG1051, pigweed and ageratum promoted reduction of the germination index in relation to the control with distilled water. The germination percentage was affected by ageratum extract (82.5% less than the control). All extracts and the surfactant Tween 80 promoted inhibition lettuce seedling growth with reduction of root length between 9.53 and 14.83 mm and hypocotyls between 21.64 to 30.95 mm

Multiple Sclerosis-Secondary Progressive Multi-Arm Randomisation Trial (MS-SMART): A multiarm phase IIb randomised, double-blind, placebo-controlled clinical trial comparing the efficacy of three neuroprotective drugs in secondary progressive multiple sclerosis

Introduction The major unmet need in multiple sclerosis (MS) is for neuroprotective therapies that can slow (or ideally stop) the rate of disease progression. The UK MS Society Clinical Trials Network (CTN) was initiated in 2007 with the purpose of developing a national, efficient, multiarm trial of repurposed drugs. Key underpinning work was commissioned by the CTN to inform the design, outcome selection and drug choice including animal models and a systematic review. This identified seven leading oral agents for repurposing as neuroprotective therapies in secondary progressive MS (SPMS). The purpose of the Multiple Sclerosis-Secondary Progressive Multi-Arm Randomisation Trial (MS-SMART) will be to evaluate the neuroprotective efficacy of three of these drugs, selected with distinct mechanistic actions and previous evidence of likely efficacy, against a common placebo arm. The interventions chosen were: amiloride (acid-sensing ion channel antagonist); fluoxetine (selective serotonin reuptake inhibitor) and riluzole (glutamate antagonist). Methods and analysis Patients with progressing SPMS will be randomised 1:1:1:1 to amiloride, fluoxetine, riluzole or matched placebo and followed for 96 weeks. The primary outcome will be the percentage brain volume change (PBVC) between baseline and 96 weeks, derived from structural MR brain imaging data using the Structural Image Evaluation, using Normalisation, of Atrophy method. With a sample size of 90 per arm, this will give 90% power to detect a 40% reduction in PBVC in any active arm compared with placebo and 80% power to detect a 35% reduction (analysing by analysis of covariance and with adjustment for multiple comparisons of three 1.67% two-sided tests), giving a 5% overall two-sided significance level. MS-SMART is not powered to detect differences between the three active treatment arms. Allowing for a 20% dropout rate, 110 patients per arm will be randomised. The study will take place at Neuroscience centres in England and Scotland. Ethics and dissemination MS-SMART was approved by the Scotland A Research Ethics Committee on 13 January 2013 (REC reference: 13/SS/0007). Results of the study will be submitted for publication in a peer-reviewed journal. Trial registration numbers NCT01910259; 2012-005394-31; ISRCTN28440672