Background: Erythropoietin (EPO) and its receptor play a major role in embryonic brain, are weakly expressed in normal postnatal/adult brain and up-regulated upon metabolic stress. EPO protects neurons from hypoxic/ ischemic injury. The objective of this trial is to study the safety and efficacy of recombinant human EPO (rhEPO) for treatment of ischemic stroke in man. Materials and Methods: The trial consisted of a safety part and an efficacy part. In the safety study, 13 patients received rhEPO intravenously (3.3 ϫ 10 4 IU/50 ml/30 min) once daily for the first 3 days after stroke. In the double-blind randomized proof-of-concept trial, 40 patients received either rhEPO or saline. Inclusion criteria were age Ͻ80 years, ischemic stroke within the middle cerebral artery territory confirmed by diffusion-weighted MRI, symptom onset Ͻ8 hr before drug administration, and deficits on stroke scales. The study endpoints were functional outcome at day 30 (Barthel Index, modified Rankin scale), NIH and Scandinavian stroke scales, evolution of

Background and Purpose-Numerous preclinical findings and a clinical pilot study suggest that recombinant human erythropoietin (EPO) provides neuroprotection that may be beneficial for the treatment of patients with ischemic stroke. Although EPO has been considered to be a safe and well-tolerated drug over 2 decades, recent studies have identified increased thromboembolic complications and/or mortality risks on EPO administration to patients with cancer or chronic kidney disease. Accordingly, the double-blind, placebo-controlled, randomized German Multicenter EPO Stroke Trial (Phase II/III; ClinicalTrials.gov Identifier: NCT00604630) was designed to evaluate efficacy and safety of EPO in stroke. Methods-This clinical trial enrolled 522 patients with acute ischemic stroke in the middle cerebral artery territory (intent-to-treat population) with 460 patients treated as planned (per-protocol population). Within 6 hours of symptom onset, at 24 and 48 hours, EPO was infused intravenously (40 000 IU each). Systemic thrombolysis with recombinant tissue plasminogen activator was allowed and stratified for. Results-Unexpectedly, a very high number of patients received recombinant tissue plasminogen activator (63.4%). On analysis of total intent-to-treat and per-protocol populations, neither primary outcome Barthel Index on Day 90 (Pϭ0.45) nor any of the other outcome parameters showed favorable effects of EPO. There was an overall death rate of 16.4% (nϭ42 of 256) in the EPO and 9.0% (nϭ24 of 266) in the placebo group (OR, 1.98; 95% CI, 1.16 to 3.38; Pϭ0.01) without any particular mechanism of death unexpected after stroke. Conclusions-Based on analysis of total intent-to-treat and per-protocol populations only, this is a negative trial that also raises safety concerns, particularly in patients receiving systemic thrombolysis. (Stroke. 2009;40:e647-e656.)

Schizophrenia is increasingly recognized as a neurodevelopmental disease with an additional degenerative component, comprising cognitive decline and loss of cortical gray matter. We hypothesized that a neuroprotective/neurotrophic add-on strategy, recombinant human erythropoietin (rhEPO) in addition to stable antipsychotic medication, may be able to improve cognitive function even in chronic schizophrenic patients. Therefore, we designed a doubleblind, placebo-controlled, randomized, multicenter, proof-of-principle (phase II) study. This study had a total duration of 2 years and an individual duration of 12 weeks with an additional safety visit at 16 weeks. Chronic schizophrenic men (N = 39) with defined cognitive deficit (X1 s.d. below normal in the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)), stable medication and disease state, were treated for 3 months with a weekly short (15 min) intravenous infusion of 40 000 IU rhEPO (N = 20) or placebo (N = 19). Main outcome measure was schizophrenia-relevant cognitive function at week 12. The neuropsychological test set (RBANS subtests delayed memory, language-semantic fluency, attention and Wisconsin Card Sorting Test (WCST-64) -perseverative errors) was applied over 2 days at baseline, 2 weeks, 4 weeks and 12 weeks of study participation. Both placebo and rhEPO patients improved in all evaluated categories. Patients receiving rhEPO showed a significant improvement over placebo patients in schizophrenia-related cognitive performance (RBANS subtests, WCST-64), but no effects on psychopathology or social functioning. Also, a significant decline in serum levels of S100B, a glial damage marker, occurred upon rhEPO. The fact that rhEPO is the first compound to exert a selective and lasting beneficial effect on cognition should encourage new treatment strategies for schizophrenia.

Amyotrophic lateral sclerosis (ALS) is the collective term for a fatal motoneuron disease of different etiologies, with oxidative stress as a common molecular denominator of disease progression. Melatonin is an amphiphilic molecule with a unique spectrum of antioxidative effects not conveyed by classical antioxidants. In preparation of a possible future clinical trial, we explored the potential of melatonin as neuroprotective compound and antioxidant in: (1) cultured motoneuronal cells (NSC-34), (2) a genetic mouse model of ALS (SOD1(G93A)-transgenic mice), and (3) a group of 31 patients with sporadic ALS. We found that melatonin attenuates glutamate-induced cell death of cultured motoneurons. In SOD1(G93A)-transgenic mice, high-dose oral melatonin delayed disease progression and extended survival. In a clinical safety study, chronic high-dose (300 mg/day) rectal melatonin was well tolerated during an observation period of up to 2 yr. Importantly, circulating serum protein carbonyls, which provide a surrogate marker for oxidative stress, were elevated in ALS patients, but were normalized to control values by melatonin treatment. This combination of preclinical effectiveness and proven safety in humans suggests that high-dose melatonin is suitable for clinical trials aimed at neuroprotection through antioxidation in ALS.

Terahertz time domain spectroscopy (TDS) was assessed as a nondestructive evaluation technique for aircraft composites. Damage to glass fiber was studied including voids, delaminations, mechanical damage, and heat damage. Measurement of the material properties on samples with localized heat damage showed that burning did not change the refractive index or absorption coefficient noticeably; however, material blistering was detected. Voids were located by TDS transmissive imaging using amplitude and phase techniques. The depth of delaminations was measured via the timing of Fabry-Perot reflections after the main pulse. Evidence of bending stress damage and simulated hidden cracks was also detected with terahertz imaging.

Three HTPB-based rocket propellant formulations containing ammonium perchlorate and aluminum particles, with different aluminum content and particle size, have been manufactured. The study has focused on the change of mechanical properties with aging time by using dynamic mechanical analysis (DMA). Therefore, propellant formulations underwent an accelerated aging program, in air (RH<10 %), between 60 °C and 90 °C with aging time adjusted to a thermal equivalent load of 15 to 20 years at 25 °C. DMA investigations revealed distinct changes in the shape of the loss factor curve. These curves were modeled with three exponentially modified Gaussian (EMG) functions in order to get the molecular interpretation of the involved aging phenomena by separating the binder fractions with different mobility. Aging of propellant formulations can be followed by considering only two parameters: the areas of the second and third loss factor transition peaks (A2, A3), and the corresponding maximum temperature values of the assigned Gauss peaks (Tc2, Tc3)

We report a pulsed Raman laser at 1193 nm based on synthetic diamond crystals with a record output power of 24.5 W and a slope efficiency of 57%. We compared the performance of an anti-reflection coated crystal at normal incidence with a Brewster cut sample. Raman oscillation was achieved at both room temperature and under cryogenic operation at 77 K. Modeling of these experiments allowed us to confirm the value of Raman gain coefficient of diamond, which was found to be 13.5 ± 2.0 cm/GW for a pump wavelength of 1030 nm.

a b s t r a c tTerahertz time domain spectroscopy in reflection configuration was assessed as a nondestructive evaluation technique for aircraft glass fiber composites. A technique for measuring the material properties of glass fiber composites using reflection geometry was demonstrated in addition to imaging of damaged glass fiber composites. Surface defects such as localized burn damage, puncture holes, and paint/composite removal were detected using amplitude and phase imaging methods. Hidden voids were also detected using the relative amplitude of the first Fabry-Perot reflection. The depths of discontinuities were then measured using a Fourier technique and then subtracting the incident pulse from the reflected pulse. Finally, nondestructive evaluation techniques for transmission and reflection configurations were compared.Published by Elsevier Ltd.