Regulatory Science and Innovation Programme for Europe (ReScIPE):A proposed model

Regulatory science underpins the objective evaluation of medicinal products. It is therefore imperative that regulatory science and expertise remain at the cutting edge so that innovations of ever-increasing complexity are translated safely and swiftly into effective, high-quality therapies. We undertook a comprehensive examination of the evolution of science and technology impacting on medicinal product evaluation over the next 5–10 years and this horizon-scanning activity was complemented by extensive stakeholder interviews, resulting in a number of significant recommendations. Highlighted in particular was the need for expertise and regulatory science research to fill knowledge gaps in both more fundamental, longer-term research, with respect to technological and product-specific challenges. A model is proposed to realise these objectives in Europe, comprising a synergistic relationship between the European Medicines Agency, the European Medicines Regulatory Network and academic research centres to establish a novel regulatory science and innovation platform.</p

High stakes and low bars: How international recognition shapes the conduct of civil wars

When rebel groups engage incumbent governments in war for control of the state, questions of international recognition arise. International recognition determines which combatants can draw on state assets, receive overt military aid, and borrow as sovereigns—all of which can have profound consequences for the military balance during civil war. How do third-party states and international organizations determine whom to treat as a state's official government during civil war? Data from the sixty-one center-seeking wars initiated from 1945 to 2014 indicate that military victory is not a prerequisite for recognition. Instead, states generally rely on a simple test: control of the capital city. Seizing the capital does not foreshadow military victory. Civil wars often continue for many years after rebels take control and receive recognition. While geopolitical and economic motives outweigh the capital control test in a small number of important cases, combatants appear to anticipate that holding the capital will be sufficient for recognition. This expectation generates perverse incentives. In effect, the international community rewards combatants for capturing or holding, by any means necessary, an area with high concentrations of critical infrastructure and civilians. In the majority of cases where rebels contest the capital, more than half of its infrastructure is damaged or the majority of civilians are displaced (or both), likely fueling long-term state weakness

Regulatory Science and Innovation Programme for Europe (ReScIPE):A proposed model

Regulatory science underpins the objective evaluation of medicinal products. It is therefore imperative that regulatory science and expertise remain at the cutting edge so that innovations of ever-increasing complexity are translated safely and swiftly into effective, high-quality therapies. We undertook a comprehensive examination of the evolution of science and technology impacting on medicinal product evaluation over the next 5-10 years and this horizon-scanning activity was complemented by extensive stakeholder interviews, resulting in a number of significant recommendations. Highlighted in particular was the need for expertise and regulatory science research to fill knowledge gaps in both more fundamental, longer-term research, with respect to technological and product-specific challenges. A model is proposed to realise these objectives in Europe, comprising a synergistic relationship between the European Medicines Agency, the European Medicines Regulatory Network and academic research centres to establish a novel regulatory science and innovation platform.</p

Precise measurements help gauge Pacific Northwest\u27s Earthquake potential

Except for the recent rumblings of a few moderate earthquakes and the eruption of Mt. St. Helen\u27s, all has been relatively quiet on the Pacific Northwestern front. The Cascades region in the Pacific Northwest, a sporadically active earthquake and volcanic zone, still has great seismic potential [Atwater, 1987], as comparisons with other subduction zones around the world have shown [Heaton and Kanamori, 1984]. Recent tsunami propagation models [Satake, 1996] and tree ring studies suggest that the last great Cascadia earthquake occurred in the winter of 1700 A.D. and had a magnitude of −8.9. The North Cascades or Wenatchee earthquake followed in 1872. With an estimated magnitude greater than 7, it was the largest earthquake in the written history of Washington and Oregon

Stability and Stabilization of Relative Equilibria of Dumbbell Bodies in Central Gravity

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/77368/1/AIAA-10546-792.pd

Support and Assessment for Fall Emergency Referrals (SAFER) 2: a cluster randomised trial and systematic review of clinical effectiveness and cost-effectiveness of new protocols for emergency ambulance paramedics to assess older people following a fall with referral to community-based care when appropriate.

BACKGROUND: Emergency calls are frequently made to ambulance services for older people who have fallen, but ambulance crews often leave patients at the scene without any ongoing care. We evaluated a new clinical protocol which allowed paramedics to assess older people who had fallen and, if appropriate, refer them to community-based falls services. OBJECTIVES: To compare outcomes, processes and costs of care between intervention and control groups; and to understand factors which facilitate or hinder use. DESIGN: Cluster randomised controlled trial. PARTICIPANTS: Participating paramedics at three ambulance services in England and Wales were based at stations randomised to intervention or control arms. Participants were aged 65 years and over, attended by a study paramedic for a fall-related emergency service call, and resident in the trial catchment areas. INTERVENTIONS: Intervention paramedics received a clinical protocol with referral pathway, training and support to change practice. Control paramedics continued practice as normal. OUTCOMES: The primary outcome comprised subsequent emergency health-care contacts (emergency admissions, emergency department attendances, emergency service calls) or death at 1 month and 6 months. Secondary outcomes included pathway of care, ambulance service operational indicators, self-reported outcomes and costs of care. Those assessing outcomes remained blinded to group allocation. RESULTS: Across sites, 3073 eligible patients attended by 105 paramedics from 14 ambulance stations were randomly allocated to the intervention group, and 2841 eligible patients attended by 110 paramedics from 11 stations were randomly allocated to the control group. After excluding dissenting and unmatched patients, 2391 intervention group patients and 2264 control group patients were included in primary outcome analyses. We did not find an effect on our overall primary outcome at 1 month or 6 months. However, further emergency service calls were reduced at both 1 month and 6 months; a smaller proportion of patients had made further emergency service calls at 1 month (18.5% vs. 21.8%) and the rate per patient-day at risk at 6 months was lower in the intervention group (0.013 vs. 0.017). Rate of conveyance to emergency department at index incident was similar between groups. Eight per cent of trial eligible patients in the intervention arm were referred to falls services by attending paramedics, compared with 1% in the control arm. The proportion of patients left at scene without further care was lower in the intervention group than in the control group (22.6% vs. 30.3%). We found no differences in duration of episode of care or job cycle. No adverse events were reported. Mean cost of the intervention was £17.30 per patient. There were no significant differences in mean resource utilisation, utilities at 1 month or 6 months or quality-adjusted life-years. In total, 58 patients, 25 paramedics and 31 stakeholders participated in focus groups or interviews. Patients were very satisfied with assessments carried out by paramedics. Paramedics reported that the intervention had increased their confidence to leave patients at home, but barriers to referral included patients' social situations and autonomy. CONCLUSIONS: Findings indicate that this new pathway may be introduced by ambulance services at modest cost, without risk of harm and with some reductions in further emergency calls. However, we did not find evidence of improved health outcomes or reductions in overall NHS emergency workload. Further research is necessary to understand issues in implementation, the costs and benefits of e-trials and the performance of the modified Falls Efficacy Scale. TRIAL REGISTRATION: Current Controlled Trials ISRCTN60481756 and PROSPERO CRD42013006418. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 13. See the NIHR Journals Library website for further project information

Measured and Simulated Nitrous Oxide Emissions from Ryegrass- and Ryegrass/White Clover-Based Grasslands in a Moist Temperate Climate

There is uncertainty about the potential reduction of soil nitrous oxide (N2O) emission when fertilizer nitrogen (FN) is partially or completely replaced by biological N fixation (BNF) in temperate grassland. The objectives of this study were to 1) investigate the changes in N2O emissions when BNF is used to replace FN in permanent grassland, and 2) evaluate the applicability of the process-based model DNDC to simulate N2O emissions from Irish grasslands. Three grazing treatments were: (i) ryegrass (Lolium perenne) grasslands receiving 226 kg FN ha−1 yr−1 (GG+FN), (ii) ryegrass/white clover (Trifolium repens) grasslands receiving 58 kg FN ha−1 yr−1 (GWC+FN) applied in spring, and (iii) ryegrass/white clover grasslands receiving no FN (GWC-FN). Two background treatments, un-grazed swards with ryegrass only (G–B) or ryegrass/white clover (WC–B), did not receive slurry or FN and the herbage was harvested by mowing. There was no significant difference in annual N2O emissions between G–B (2.38±0.12 kg N ha−1 yr−1 (mean±SE)) and WC-B (2.45±0.85 kg N ha−1 yr−1), indicating that N2O emission due to BNF itself and clover residual decomposition from permanent ryegrass/clover grassland was negligible. N2O emissions were 7.82±1.67, 6.35±1.14 and 6.54±1.70 kg N ha−1 yr−1, respectively, from GG+FN, GWC+FN and GWC-FN. N2O fluxes simulated by DNDC agreed well with the measured values with significant correlation between simulated and measured daily fluxes for the three grazing treatments, but the simulation did not agree very well for the background treatments. DNDC overestimated annual emission by 61% for GG+FN, and underestimated by 45% for GWC-FN, but simulated very well for GWC+FN. Both the measured and simulated results supported that there was a clear reduction of N2O emissions when FN was replaced by BNF

Regulation of the host immune system by helminth parasites

Helminth parasite infections are associated with a battery of immunomodulatory mechanisms, which impact all facets of the host immune response to ensure their persistence within the host. This broad-spectrum modulation of host immunity has intended and unintended consequences, both advantageous and disadvantageous. Thus the host may benefit from suppression of collateral damage during parasite infection, and from reduced allergic, autoimmune and inflammatory reactions. However, helminth infection can also be detrimental in reducing vaccine responses, increasing susceptibility to co-infection, and potentially reducing tumor immunosurveillance. In this review we will summarize the panoply of immunomodulatory mechanisms used by helminths, their potential utility in human disease, and prospective areas of future research