Improvement in edema and cognitive recovery after moderate traumatic brain injury with the neurosteroid prodrug NTS-104.

Neuroactive steroids reduce mortality, decrease edema, and improve functional outcomes in preclinical and clinical traumatic brain injury (TBI) studies. In this study, we tested the efficacy of two related novel neuroactive steroids, NTS-104 and NTS-105, in a rat model of TBI. NTS-104 is a water-soluble prodrug of NTS-105, a partial progesterone receptor agonist.

NTS-105 decreased cell death and preserved long-term potentiation in an in vitro model of moderate traumatic brain injury.

Traumatic brain injury (TBI) is a major cause of hospitalization and death. To mitigate these human costs, the search for effective drugs to treat TBI continues. In the current study, we evaluated the efficacy of the novel neurosteroid, NTS-105, to reduce post-traumatic pathobiology in an in vitro model of moderate TBI that utilizes an organotypic hippocampal slice culture.

Phase-Assisted Tailored Conductivity of Doped Ceria Electrolytes to Boost SOFC Performance.

Efforts to lower the operating temperature of solid oxide fuel cells include producing electrolytes that are sufficiently conductive and stable below 600 °C. Doped ceria is one such electrolyte being considered. During this study, codoped ceria powders (CeSmMO, M = Bi, Zn and = 0, 0.

The impact of university STEM assets: A systematic review of the empirical evidence.

Background: Innovation ecosystems are an important driver of regional economic growth and development. STEM assets connected to universities may play an important role in such ecosystems.

Objective: To systematically review the literature relating to the effect of university STEM assets on regional economies and innovation ecosystems, providing a better understanding of how the impact is generated and constrained, as well as identifying any gaps in knowledge.

Robust Arduino controlled spin coater using a novel and simple gravity chuck design.

Spin coaters offer an invaluable method of thin film fabrication. Various implementations, both proprietary and open-source exist, offering vacuum and gravity samples chucks. These implementations vary in their reliability, ease-of-use, cost, and versatility.

A New Hydrometallurgical Process for Metal Extraction from Electric Arc Furnace Dust Using Ionic Liquids.

This research proposes a new hydrometallurgical method for Zn, In, and Ga extraction, along with Fe as a common impurity, from electric arc furnace dust (EAFD), using ionic liquids. EAFD is a metal-containing waste fraction generated in significant amounts during the process of steelmaking from scrap material in an electric arc furnace. With valuable metal recovery as the main goal, two ionic liquids, [BmimHSO] and [BmimCl], were studied in conjunction with three oxidants: Fe(SO), KMnO, and HO.

The influence of the Li addition rate during the hydrothermal synthesis of LiFePO on the average and local structure.

A hydrothermal method was used to synthesize LiFePO to explore the effect of the rate of addition of the Li precursor to a mixture of the Fe and PO precursors. Both the average and local structures were investigated using powder X-ray diffraction, Mössbauer spectroscopy and X-ray absorption spectroscopy. Slower addition rates led to increased oxidation of Fe to Fe despite purging all solutions constantly, as well as increased defects.

Pharmacological Characterization of a Novel Neuroactive Steroid Prodrug, NTS-104, and Its Neuroprotective Activity in Experimental Stroke Models.

Background: Ischemic stroke affects about 700 000 patients per year in the United States, and to date, there are no effective pharmacological agents that promote recovery. Here, we studied the pharmacokinetics, pharmacodynamics, and efficacy of NTS-105, a novel neuroactive steroid, and NTS-104, a prodrug of NTS-105, in 2 models of ischemic stroke.

Methods: The pharmacodynamics and pharmacokinetics of NTS-104/105 were investigated in naive and stroke rats, and models of embolic and transient middle cerebral artery occlusion were used to investigate the dose-related effects of NTS-104.

The Kinetics of Pyrite Dissolution in Nitric Acid Solution.

Refractory sulphidic ore with gold captured in pyrite has motivated researchers to find efficient means to break down pyrite to make gold accessible and, ultimately, improve gold extraction. Thus, the dissolution of pyrite was investigated to understand the mechanism and find the corresponding kinetics in a nitric acid solution. To carry this out, the temperature (25 to 85 °C), nitric acid concentration (1 to 4 M), the particle size of pyrite from 53 to 212 µm, and different stirring speeds were examined to observe their effect on pyrite dissolution.

Probing the stoichiometry dependent catalytic activity of nickel selenide counter electrodes in the redox reaction of iodide/triiodide electrolyte in dye sensitized solar cells.

Nickel selenide (Ni Se ) systems have received much attention in recent years as potential low cost counter electrodes (CEs) in dye sensitized solar cells (DSSCs). Their electrocatalytic activities are comparable to that of the conventional platinum CE. Despite their achievements, the effect of stoichiometry on their catalytic performance as CEs in DSSCs still remains unclear, hence the motivation for this work.

Multiple-dose ponezumab for mild-to-moderate Alzheimer's disease: Safety and efficacy.

Introduction: Multiple intravenous doses of ponezumab, an anti-amyloid antibody, were evaluated in subjects with mild-to-moderate Alzheimer's disease (AD).

Methods: In part A, 77 subjects were randomized to ponezumab 0.1, 0.

Features of lineage-specific hematopoietic metabolism revealed by mitochondrial proteomics.

Hematopoietic bone marrow is a regenerative tissue of high clinical relevance, yet relatively little is known about the metabolism of the stem and progenitor populations concerned. We have used a multipotent murine cell line to generate sufficient numbers of cells undergoing self-renewal, erythroid or myeloid differentiation to allow a proteomics analysis of enriched mitochondria. Stringent analysis identified 37 mitochondria-associated proteins changing on differentiation in this system.

Application of Protocols Devised to Study Bi(III) Complex Formation by Voltammetry: The Bi(III)-Picolinic Acid System.

Bi(III) coordination chemistry has been largely neglected due to the difficulties faced when studying these systems even though Bi(III) is used in various medicinal applications. This study of the Bi(III)-picolinic acid system by voltammetry applies the rigorous methodologies already developed to enable the study of Bi(III) systems starting in very acidic solutions to prevent precipitation. This includes calibrating the glass electrode accurately at these low pHs, compensating for the diffusion junction potential below pH 2 and determining the reduction potential of uncomplexed Bi(III) which cannot be directly measured.

Measurements and Modeling To Determine the Reduction Potential of Uncomplexed Bi(III) in Nitrate Solutions for Application in Bi(III)-Ligand Equilibria Studies by Voltammetry.

The free metal ion potential, E(M), is a critical parameter in the calculation of formation constants when using voltammetry. When studying complex formation of Bi(III), however, E(Bi) cannot be directly measured. In this work a nitrate background electrolyte was employed to obtain reversible reduction waves.

Development of a straightforward and sensitive scale for MCI and early AD clinical trials.

Background: Although the Clinical Dementia Rating Scale-Sum of Boxes score (CDR-SB) is a widely accepted and commonly used global scale, validated clinical endpoints of cognitive changes are unavailable in the predementia stages of Alzheimer's disease (AD), and a new clinical assessment with reliability and sensitivity is needed in the mild cognitive impairment (MCI) population.

Methods: Using Alzheimer's Disease Neuroimaging Initiative (ADNI)-1/GO data, signal-to-noise ratios (SNRs) were calculated to quantify the sensitivity of a measure for detecting disease progression and hypothetical treatment effects. All possible combinations of selected sensitive measures were assessed for developing composite scores.

A multicenter, double-blind, placebo-controlled trial of the PDE9A inhibitor, PF-04447943, in Alzheimer's disease.

Background: PF-04447943 is a potent, selective phosphodiesterase 9A (PDE9A) inhibitor that elevates guanoscine 3',5' - cyclic monophosphate (cGMP) in brain and cerebrospinal fluid. PDE9A inhibition enhances synaptic plasticity and improves memory in preclinical cognition models, and prevents decreases in dendritic spine density in transgenic mice that overexpress amyloid precursor protein (APP) leading to high levels of amyloid beta (Aβ) production (Tg2576).

Objective: This Phase 2 multicenter study was designed to assess the efficacy, safety and pharmacokinetics of PF-04447943 compared with placebo in mild to moderate probable Alzheimer's disease (AD).

Safety and pharmacology of a single intravenous dose of ponezumab in subjects with mild-to-moderate Alzheimer disease: a phase I, randomized, placebo-controlled, double-blind, dose-escalation study.

Objectives: Ponezumab is a humanized antiamyloid beta (Aβ) monoclonal antibody designed to treat Alzheimer disease (AD).

Methods: This randomized, double-blind, single-dose-escalation study evaluated the safety, pharmacokinetics, and pharmacodynamics of 0.1, 0.

The efficacy and safety of varenicline for smoking cessation using a flexible dosing strategy in adult smokers: a randomized controlled trial.

Objective: To determine whether self-regulated flexible dosing with varenicline tartrate is safe and effective for smoking cessation.

Research Design And Methods: 320 healthy, motivated-to-quit smokers (> or =10 cigarettes/day) aged 18-65 years, entered a multicenter, randomized, double-blind, placebo-controlled study - conducted between December 26, 2001 and June 24, 2003 - with a 12-week treatment phase and 40-week, double-blind, non-treatment follow-up. Treatment consisted of varenicline or placebo in fixed doses (Week 1: titrated from 0.

Varenicline versus bupropion SR or placebo for smoking cessation: a pooled analysis.

Objectives: To evaluate varenicline's efficacy for smoking cessation versus bupropion SR and placebo and to explore whether factors typically predictive of abstinence influence varenicline's efficacy versus placebo, as measured by the week 9-12 continuous abstinence rate (CAR9-12).

Methods: Smokers in 2 randomized, placebo-controlled trials received varenicline 1 mg BID (n=696), bupropion SR 150 mg BID (n=671), or placebo (n=685) for 12 weeks. Nontreatment followup lasted 40 weeks.

Human abuse liability of the smoking cessation drug varenicline in smokers and nonsmokers.

Varenicline is an alpha(4)beta(2) nicotinic acetylcholine receptor partial agonist developed as an aid for smoking cessation. This study evaluated varenicline's potential for abuse by smokers (n = 23) and nonsmokers (n = 22). The study used a randomized, double-blind, placebo-controlled, double-dummy crossover design with five treatment periods: 15 and 30 mg amphetamine, 1 and 3 mg varenicline, and placebo.

Varenicline versus transdermal nicotine patch for smoking cessation: results from a randomised open-label trial.

Background: Varenicline, a new treatment for smoking cessation, has demonstrated significantly greater efficacy over placebo and sustained release bupropion (bupropion SR). A study was undertaken to compare a 12-week standard regimen of varenicline with a 10-week standard regimen of transdermal nicotine replacement therapy (NRT) for smoking cessation.

Methods: In this 52-week, open-label, randomised, multicentre, phase 3 trial conducted in Belgium, France, The Netherlands, UK and USA, participants were randomly assigned (1:1) to receive varenicline uptitrated to 1 mg twice daily for 12 weeks or transdermal NRT (21 mg/day reducing to 7 mg/day) for 10 weeks.

Should troponin and creatinine kinase be routinely measured after vascular surgery?

The current guidelines for the evaluation and prediction of adverse cardiovascular events (CVEs) following vascular surgery in high-risk patients recommends serial electrocardiograms (ECGs) but not biomarkers such as cTn-I and CK-MB. The objective of this study was to determine whether biomarkers should be routinely measured in high-risk patients undergoing vascular surgery. A multicenter, prospective study with investigators blinded to core laboratory results was conducted.

A randomized, placebo-controlled trial of varenicline, a selective alpha4beta2 nicotinic acetylcholine receptor partial agonist, as a new therapy for smoking cessation in Asian smokers.

Background: Rates of smoking in East Asian men range from >35% to >60%, and are increasing in women and the young.

Objective: This study evaluated the efficacy and tolerability of 1 mg BID varenicline, a novel alpha4beta2 nicotinic acetylcholine receptor partial agonist, for smoking cessation in smokers in Taiwan and Korea.

Methods: A randomized, double-blind, placebo-controlled, 12-week treatment, 12-week follow-up trial was conducted at 5 sites each in Korea and Taiwan.

A double-blind study evaluating the long-term safety of varenicline for smoking cessation.

Objective: We assessed the safety of long-term varenicline administration for smoking cessation.

Methods: In this randomized, double-blind, multicenter trial, eligible adult smokers (18-75 years) who smoked an average of > or =10 cigarettes/day were randomized to either varenicline 1 mg twice daily (BID) or placebo for 52 weeks. Subjects made weekly clinic visits until week 8, and then every 4 weeks until week 52, with a follow-up visit at week 53.