Exploring Regulatory Flexibility to Create Novel Incentives to Optimize Drug Discovery

Efforts by governments, firms, and patients to deliver pioneering drugs for critical health needs face a challenge of diminishing efficiency in developing those medicines. While multi-sectoral collaborations involving firms, researchers, patients, and policymakers are widely recognized as crucial for countering this decline, existing incentives to engage in drug development predominantly target drug manufacturers and thereby do little to stimulate collaborative innovation. In this mini review, we consider the unexplored potential within pharmaceutical regulations to create novel incentives to encourage a diverse set of actors from the public and private spheres to engage in the kind of collaborative knowledge exchange requisite for fostering enhanced innovation in early drug development

Innovative interstellar explorer

An interstellar "precursor" mission has been under discussion in the scientific community for at least 30 years. Fundamental scientific questions about the interaction of the Sun with the interstellar medium can only be answered with in situ measurements that such a mission can provide. The Innovative Interstellar Explorer (IIE) and its use of Radioisotope Electric Propulsion (REP) is being studied under a NASA "Vision Mission" grant. Speed is provided by a combination of a high-energy launch, using current launch vehicle technology, a Jupiter gravity assist, and long-term, low-thrust, continuous acceleration provided by an ion thruster running off electricity provided by advanced radioisotope electric generators. A payload of ten instruments with an aggregate mass of ~35 kg and requiring ~30 W has been carefully chosen to address the compelling science questions. The nominal 20-day launch window opens on 22 October 2014 followed by a Jupiter gravity assist on 5 February 2016. The REP system accelerates the spacecraft to a "burnout" speed of 7.8 AU per year at 104 AU on 13 October 2032 (Voyager 1's current speed is ~3.6 AU/yr). The spacecraft will return at least 500 bits per second from at least 200 AU ~30 years after launch. Additional (backup) launch opportunities occur every 13 months to early 2018. In addition to addressing basic heliospheric science, the mission will ensure continued information on the far-heliospheric galactic cosmic ray population after the Voyagers have fallen silent and as the era of human Mars exploration begins

The relationship between indoleamine 2,3-dioxygenase activity and post-stroke cognitive impairment

BACKGROUND: Activation of indoleamine 2,3-dioxygenase (IDO) and higher concentrations of several kynurenine metabolites have been observed post-stroke, where they have been associated with increased mortality. While lower tryptophan or a higher ratio of kynurenine/tryptophan (K/T) in peripheral blood have been associated with dementia and the severity of cognitive symptoms in Alzheimer's disease, the association between K/T ratios and post-stroke cognitive impairment (PSCI) has not been investigated. METHODS: Patients were recruited from the acute stroke unit of a general hospital within 1 month post-stroke. Assessments included the Standardized Mini-Mental State Examination (sMMSE) for cognition, the National Institutes of Health Stroke Scale (NIHSS) for stroke severity, and the Center for Epidemiological Studies-Depression Scale (CES-D) for depressive symptoms. Tryptophan and kynurenine concentrations were determined by high-performance liquid chromatography. RESULTS: A total of 41 patients with ischemic stroke ([mean ± SD] age 72.3 ± 12.2 years, 53.7% male, sMMSE 25.6 ± 4.1, NIHSS 7.27 ± 5.55) were recruited. Higher K/T ratios were associated with lower post-stroke global cognition (i.e. sMMSE scores; β = -.327, P = .037). A backward stepwise elimination linear regression (F(1,40)=6.15, P=.005, adjusted R(2)=.205) showed that the highest K/T ratio tertile (β = -.412, P = .006) predicted lower sMMSE scores, controlling for age (β = -.253, p = .081), with NIHSS (β = -.027, P = 0.859), and lesion volume (β = -.066, P = 0.659) removed from the model. In receiver operating characteristic analysis, a K/T ratio of 78.3 μmol/mmol (top tertile) predicted significant cognitive impairment (sMMSE score ≤ 24) with 67% sensitivity and 86% specificity (area under the curve = 0.730, p = .022). CONCLUSIONS: These data suggest an inflammatory response characterized by IDO activation may be relevant to the development of PSCI. Since the neuroactivity of kynurenine metabolites may be amenable to pharmacotherapeutic intervention, the K/T ratio may be a clinically important biomarker

White Matter Hyperintensity Regression: Comparison of Brain Atrophy and Cognitive Profiles with Progression and Stable Groups

Subcortical white matter hyperintensities (WMHs) in the aging population frequently represent vascular injury that may lead to cognitive impairment. WMH progression is well described, but the factors underlying WMH regression remain poorly understood. A sample of 351 participants from the Alzheimer’s Disease Neuroimaging Initiative 2 (ADNI2) was explored who had WMH volumetric quantification, structural brain measures, and cognitive measures (memory and executive function) at baseline and after approximately 2 years. Selected participants were categorized into three groups based on WMH change over time, including those that demonstrated regression (n = 96; 25.5%), stability (n = 72; 19.1%), and progression (n = 209; 55.4%). There were no significant differences in age, education, sex, or cognitive status between groups. Analysis of variance demonstrated significant differences in atrophy between the progression and both regression (p = 0.004) and stable groups (p = 0.012). Memory assessments improved over time in the regression and stable groups but declined in the progression group (p = 0.003; p = 0.018). WMH regression is associated with decreased brain atrophy and improvement in memory performance over two years compared to those with WMH progression, in whom memory and brain atrophy worsened. These data suggest that WMHs are dynamic and associated with changes in atrophy and cognition

The experience of long-term opiate maintenance treatment and reported barriers to recovery: A qualitative systematic review

Background/Aim: To inform understanding of the experience of long-term opiate maintenance and identify barriers to recovery. Methods: A qualitative systematic review. Results: 14 studies in 17 papers, mainly from the USA (65%), met inclusion criteria, involving 1,088 participants. Studies focused on methadone prescribing. Participants reported stability; however, many disliked methadone. Barriers to full recovery were primarily ‘inward focused'. Conclusion: This is the first review of qualitative literature on long-term maintenance, finding that universal service improvements could be made to address reported barriers to recovery, including involving ex-users as positive role models, and increasing access to psychological support. Treatment policies combining harm minimisation and abstinence-orientated approaches may best support individualised recovery

Ice Particle Impacts on a Moving Wedge

This work presents the results of an experimental study of ice particle impacts on a moving wedge. The experiment was conducted in the Adverse Environment Rotor Test Stand (AERTS) facility located at Penn State University. The wedge was placed at the tip of a rotating blade. Ice particles shot from a pressure gun intercepted the moving wedge and impacted it at a location along its circular path. The upward velocity of the ice particles varied from 7 to 12 meters per second. Wedge velocities were varied from 0 to 120 meters per second. Wedge angles tested were 0, 30, 45, and 60. High speed imaging combined with backlighting captured the impact allowing observation of the effect of velocity and wedge angle on the impact and the post-impact fragment behavior. It was found that the pressure gun and the rotating wedge could be synchronized to consistently obtain ice particle impacts on the target wedge. It was observed that the number of fragments increase with the normal component of the impact velocity. Particle fragments ejected immediately after impact showed velocities higher than the impact velocity. The results followed the major qualitative features observed by other researchers for hailstone impacts, even though the reduced scale size of the particles used in the present experiment as compared to hailstones was 4:1

Amici Curiae Brief for Academics in Law, Medicine, Health Policy, and Clinical Genetics in Support of Neither Party

Amicus ("friend of the court") brief written by Drs. E. Richard Gold, Tania Bubela, Robert Cook-Deegan, James Evans, Julian Kinderlerer, and Dianne Nicol, in support of neither party (Supreme Court Case Docket No. 12-398

Effects of esomeprazole treatment for gastroesophageal reflux disease on quality of life in 12- to 17-year-old adolescents: an international health outcomes study

<p>Abstract</p> <p>Background</p> <p>Although gastroesophageal reflux disease (GERD) is common in adolescents, the burden of GERD on health-related quality of life (HRQOL) in adolescents has not been previously evaluated. Therefore, the objective of the study was to examine the effect of GERD on HRQOL in adolescents.</p> <p>Methods</p> <p>This international, 31-site, 8-week safety study randomized adolescents, aged 12 to 17 years inclusive, with GERD to receive esomeprazole 20 or 40 mg once daily. The Quality of Life in Reflux and Dyspepsia questionnaire (QOLRAD), previously validated in adults, consists of 25 questions grouped into 5 domains: emotional distress, sleep disturbance, food/drink problems, physical/social functioning, and vitality. The QOLRAD was administered at the baseline and week-8 (final) visits.</p> <p>Results</p> <p>Of the 149 patients randomized, 134 completed the QOLRAD at baseline and final visits and were eligible for analysis of their HRQOL data. Baseline QOLRAD scores indicated GERD had a negative effect on the HRQOL of these adolescents, especially in the domains of vitality and emotional distress, and problems with food/drink. At the final visit, mean scores for all 5 QOLRAD domains improved significantly (<it>P </it>< .0001); change of scores (ie, delta) for all domains met or exceeded the adult QOLRAD minimal clinically significant difference standard of 0.5 units.</p> <p>Conclusion</p> <p>GERD had a negative effect on QOL in adolescents. After esomeprazole treatment, statistically and clinically significant improvements occurred in all domains of the QOLRAD for these adolescents.</p> <p>Trial Registration</p> <p>D9614C00098; ClinicalTrials.gov Identifier NCT00241501</p