Laser locking to the Hg-199 S-1(0)-P-3(0) clock transition with 5.4x10(-15)/root tau fractional frequency instability

With Hg-199 atoms confined in an optical lattice trap in the Lamb-Dicke regime, we obtain a spectral line at 265.6 nm for which the FWHM is similar to 15 Hz. Here we lock an ultrastable laser to this ultranarrow S-1(0) - P-3(0) clock transition and achieve a fractional frequency instability of 5.4 x 10(-15) / root tau for tau <= 400 s. The highly stable laser light used for the atom probing is derived from a 1062.6 nm fiber laser locked to an ultrastable optical cavity that exhibits a mean drift rate of -6.0 x 10(-17) s-(1) (-16.9 mHzs(-1) at 282 THz) over a six month period. A comparison between two such lasers locked to independent optical cavities shows a flicker noise limited fractional frequency instability of 4 x 10(-16) per cavity. (c) 2012 Optical Society of America

Performance of a poly(2,5-benzimidazole)-based polymer electrolyte membrane fuel cell

The performance of an ABPBI-based High Temperature H-2/O-2 PEMFC system was studied under different experimental conditions. Increasing the temperature from 130 to 170 degrees C improved the cell performance, even though further increase was not beneficial for the system. Humidification of the H-2 stream ameliorated this behaviour, even though operating above 170 degrees C is not advisable in terms of cell performance. A significant electrolyte dehydration seems to negatively affect the fuel cell performance, especially in the case of the anode. In the presence of 2% vol. CO in the H-2 stream, the temperature exerted a positive effect on the cell performance, reducing the strong adsorption of this poison on the platinum sites. Moreover, humidification of the H-2 + CO stream increased the maximum power densities of the cell, further alleviating the CO poisoning effects. Actual CO-O-2 fuel cell results confirmed the significant beneficial effect of the relative humidity on the kinetics of the CO oxidation process. Copyright (C) 2011, Hydrogen Energy Publications, LLC. Published by Elsevier Ltd. All rights reserved.

Cannabidiol injected into the bed nucleus of the stria terminalis reduces the expression of contextual fear conditioning via 5-HT1A receptors

Systemic administration of cannabidiol (CBD) attenuates cardiovascular and behavioral changes induced by re-exposure to a context that had been previously paired with footshocks. Previous results from our group using cFos immunohistochemistry suggested that the bed nucleus of the stria terminalis (BNST) is involved in this effect. The mechanisms of CBD effects are still poorly understood, but could involve 5-HT1A receptor activation. Thus, the present work investigated if CBD administration into the BNST would attenuate the expression of contextual fear conditioning and if this effect would involve the activation of 5-HT1A receptors. Male Wistar rats with cannulae bilaterally implanted into the BNST were submitted to a 10 min conditioning session (six footshocks, 1.5 mA/3 s). Twenty-four hours later freezing and cardiovascular responses (mean arterial pressure and heart rate) to the conditioning box were measured for 10 min. CBD (15, 30 or 60 nmol) or vehicle was administered 10 min before the re-exposure to the aversive context. The second experiment was similar to the first one except that animals received microinjections of the 5-HT1A receptor antagonist WAY100635 (0.37 nmol) 5 min before CBD (30 nmol) treatment. The results showed that CBD (30 and 60 nmol) treatment significantly reduced the freezing and attenuated the cardiovascular responses induced by re-exposure to the aversive context. Moreover, WAY100635 by itself did not change the cardiovascular and behavioral response to context, but blocked the CBD effects. These results suggest that CBD can act in the BNST to attenuate aversive conditioning responses and this effect seems to involve 5-HT1A receptor-mediated neurotransmission.

Pimavanserin, a selective serotonin (5-HT)2A-inverse agonist, enhances the efficacy and safety of risperidone, 2 mg/day, but does not enhance efficacy of haloperidol, 2 mg/day: Comparison with reference dose risperidone, 6 mg/day

Most atypical antipsychotic drugs (APDs), e. g. risperidone (RIS), produce more extensive blockade of brain serotonin (5-HT)(2A) than dopamine (DA) D-2 receptors. This distinguishes them from typical APDs, e.g. haloperidol (HAL). Our objective was to test the hypothesis that augmentation of low doses of RIS or HAL (2 mg/day) with pimavanserin (PIM), a selective 5-HT2A inverse agonist, to enhance 5-HT2A receptor blockade, can achieve efficacy comparable to RIS, 6 mg/day, but with lesser side effects. In a multi-center, randomized, double-blind, 6 week trial, 423 patients with chronic schizophrenia experiencing a recent exacerbation of psychotic symptoms were randomized to RIS2mg + placebo (RIS2PBO), RIS2mg + PIM20mg (RIS2PIM), RIS6mg + PBO (RIS6PBO), HAL2mg + PBO (HAL2PBO), or HAL2mg + PIM20mg (HAL2PIM). Improvement in psychopathology was measured by the PANSS and CGI-S. The reduction in PANSS Total Score with RIS2PIM at endpoint was significantly greater than RIS2PBO: -23.0 vs. -16.3 (p = 0.007), and not significantly different from the RIS6PBO group: -23.2 points. The percentage of patients with >= 20% improvement at day 15 in the RIS2PIM group was 62.3%, significantly greater than the RIS6PBO (42.1%; p = 0.01) and the RIS2PBO groups (37.7%; p = 0.002). Weight gain and hyperprolactinemia were greater in the RIS6PBO group than the RIS2PIM group but there was no difference in extrapyramidal side effects (EPS). HAL2PBO and HAL2PIM were not significantly different from each other in efficacy but HAL2PIM had less EPS at end point. Both HAL groups and RIS6PBO showed equal improvement in psychopathology at endpoint, indicating HAL 2 mg/day is effective to treat an acute exacerbation in chronic schizophrenia patients. In conclusion, a sub-effective RIS dose combined with PIM to enhance 5-HT2A receptor blockade provided faster onset of action, and at endpoint, equal efficacy and better safety, compared to standard dose RIS. These results support the conclusion that 5-HT2A receptor blockade is a key component of the action of some atypical APDs and can reduce EPS due to a typical APD. (C) 2012 Elsevier B.V. All rights reserved.

Cloning, production and characterization of antigen 5 like proteins from Simulium vittatum and Culicoides nubeculosus, the first cross-reactive allergen associated with equine insect bite hypersensitivity

Insect bite hypersensitivity (IBH) is an IgE-mediated seasonal dermatitis of the horses associated with bites of Simulium (black fly) and Culicoides (midge) species. Although cross-reactivity between Simulium and Culicoides salivary gland extracts has been demonstrated, the molecular nature of the allergens responsible for the observed cross-reactivity remains to be elucidated. In this report we demonstrate for the first time in veterinary medicine that a homologous allergen, present in the salivary glands of both insects, shows extended IgE cross-reactivity in vitro and in vivo. The cDNA sequences coding for both antigen 5 like allergens termed Sim v 1 and Cul n 1 were amplified by PCR, subcloned in high level expression vectors, and produced as [His](6)-tagged proteins in Escherichia coli. The highly pure recombinant proteins were used to investigate the prevalence of sensitization in IBH-affected horses by ELISA and their cross-reactive nature by Western blot analyses, inhibition ELISA and intradermal skin tests (IDT). The prevalence of sensitization to Sim v 1 and Cul n 1 among 48 IBH-affected horses was 37% and 35%, respectively. In contrast, serum IgE levels to both allergens in 24 unaffected horses did not show any value above background. Both proteins strongly bound serum IgE from IBH-affected horses in Western blot analyses, demonstrating the allergenic nature of the recombinant proteins. Extended inhibition ELISA experiments clearly showed that Sim v 1 in fluid phase is able to strongly inhibit binding of serum IgE to solid phase coated Cul n 1 in a concentration dependent manner and vice versa. This crucial experiment shows that the allergens share common IgE-binding epitopes. IDT with Sim v 1 and Cul n 1 showed clear immediate and late phase reactions to the allergen challenges IBH-affected horses, whereas unaffected control horses do not develop relevant immediate hypersensitivity reactions. In some horses, however, mild late phase reactions were observed 4h post-challenge, a phenomenon reported to occur also in challenge experiments with Simulium and Culicoides crude extracts probably related to lipopolysaccaride contaminations which are also present in E. coli-expressed recombinant proteins. In conclusion our data demonstrate that IgE-mediated cross-reactivity to homologous allergens, a well-known clinically relevant phenomenon in human allergy, also occurs in veterinary allergy.

The multicenter trial SAKK 37/95 of cladribine, cyclophosphamide and prednisone in the treatment of chronic lymphocytic leukemias and low-grade non-Hodgkin's lymphomas

A multicenter trial was performed to confirm the therapeutic efficacy and the toxicity profile of the combination of cladribine, cyclophosphamide and prednisone in low-grade non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Twenty-three adults with previously treated (61%) or untreated (39%) NHL International Working Formulation A or Binet B and C CLL were administered cladribine 0.1 mg/kg/day as a subcutaneous bolus for 5 days, intravenous cyclophosphamide 500 mg/m2 on day 1, and oral prednisone 40 mg/m2 on days 1-5, every 4 weeks. Unexpected early hematological toxicities led to dose modifications for pretreated patients who received cladribine for 3 days only up to a maximum of five courses. Responses were observed in 75%, with 7 patients obtaining a complete clinical and hematological response. Median duration of complete response was 9 months. Median time to progression or relapse was 31 months. Myelosuppression and infections were dose limiting whereas posttreatment complications, including fatalities, resulted from infections. Median overall survival time from trial entry was 60 months. Activity of the combination of cladribine, cyclophosphamide and prednisone was confirmed. However, in the specific setting of a multicenter trial, unexpected fatal infectious episodes occurred in pretreated patients. Great caution is thus required in these susceptible patients and the routine use of corticosteroids should probably be abandoned.

Direct MR arthrography at 1.5 and 3.0 T: signal dependence on gadolinium and iodine concentrations--phantom study

PURPOSE: To prospectively quantify in vitro the influence of gadopentetate dimeglumine and ioversol on the magnetic resonance (MR) imaging signal observed with a variety of musculoskeletal pulse sequences to predict optimum gadolinium concentrations for direct MR arthrography at 1.5 and 3.0 T. MATERIALS AND METHODS: In an in vitro study, T1 and T2 relaxation times of three dilution series of gadopentetate dimeglumine (concentration, 0-20.0 mmol gadolinium per liter) at ioversol concentrations with iodine concentration of 0, 236.4, and 1182 mmol iodine per liter (corresponding to 0, 30, and 150 mg of iodine per milliliter) were measured at 1.5 and 3.0 T. The relaxation rate dependence on concentrations of gadolinium and iodine was analytically modeled, and continuous profiles of signal versus gadolinium concentration were calculated for 10 pulse sequences used in current musculoskeletal imaging. After fitting to experimental discrete profiles, maximum signal-to-noise ratio (SNR), gadolinium concentration with maximum SNR, and range of gadolinium concentration with 90% of maximum SNR were derived. The overall influence of field strength and iodine concentration on these parameters was assessed by using t tests. The deviation of simulated from experimental signal-response profiles was assessed with the autocorrelation of the residuals. RESULTS: The model reproduced relaxation rates of 0.37-38.24 sec(-1), with a mean error of 4.5%. Calculated SNR profiles matched the discrete experimental profiles, with autocorrelation of the residuals divided by the mean of less than 5.0. Admixture of ioversol consistently reduced T1 and T2, narrowed optimum gadolinium concentration ranges (P = .004-.006), and reduced maximum SNR (P < .001 to not significant). Optimum gadolinium concentration was 0.7-3.4 mmol/L at both field strengths. At 3.0 T, maximum SNR was up to 75% higher than at 1.5 T. CONCLUSION: Admixture of ioversol to gadopentetate dimeglumine solutions results in a consistent additional relaxation enhancement, which can be analytically modeled to allow a near-quantitative a priori optimized match of contrast media concentrations and imaging protocol for a broad variety of pulse sequences.

Long-term follow up (37-69 years) of patients with bladder exstrophy treated with ureterosigmoidostomy: uro-nephrological outcome

OBJECTIVE: To describe the urological and nephrological long-term outcome of patients born with classical bladder exstrophy treated with bilateral ureterosigmoidostomies in early childhood. PATIENTS AND METHOD: Out of 42 patients born with bladder exstrophy in Switzerland between 1937 and 1968, 25 participated in this study; seven had died, seven were lost to follow up and three refused consent. Assessment included chart review, clinical examination, and assessment of renal function and morphology. RESULTS: After a follow-up period of 37-69 years ((mean 50 years), 13 of the 25 participants (52%) had their ureterosigmoidostomy still in place. All others had different forms of urinary diversions. Fifteen (60%) patients had normal renal function or mild chronic kidney disease as assessed by estimated glomerular filtration rate. Three patients were on renal replacement therapy. MRI (n=16) showed 10 morphologically normal kidneys. One patient suffered from adenocarcinoma of the colon, five had benign colonic polyps, one urethral papillary carcinoma and 18 no evidence of tumor. CONCLUSION: The majority of our patients have normal or mildly impaired renal function and a well functioning ureterosigmoidostomy. This is remarkable, given the fact that ureterosigmoidostomies are considered to be refluxing high-pressure reservoirs at risk of renal injury and malignancy.

Development and validation of GT3X accelerometer cut-off points in 5- to 9-year-old children based on indirect calorimetry measurements

The ActiGraph accelerometer is commonly used to measure physical activity in children. Count cut-off points are needed when using accelerometer data to determine the time a person spent in moderate or vigorous physical activity. For the GT3X accelerometer no cut-off points for young children have been published yet. The aim of the current study was thus to develop and validate count cut-off points for young children. Thirty-two children aged 5 to 9 years performed four locomotor and four play activities. Activity classification into the light-, moderate- or vigorous-intensity category was based on energy expenditure measurements with indirect calorimetry. Vertical axis as well as vector magnitude cut-off points were determined through receiver operating characteristic curve analyses with the data of two thirds of the study group and validated with the data of the remaining third. The vertical axis cut-off points were 133 counts per 5 sec for moderate to vigorous physical activity (MVPA), 193 counts for vigorous activity (VPA) corresponding to a metabolic threshold of 5 MET and 233 for VPA corresponding to 6 MET. The vector magnitude cut-off points were 246 counts per 5 sec for MVPA, 316 counts for VPA - 5 MET and 381 counts for VPA - 6 MET. When validated, the current cut-off points generally showed high recognition rates for each category, high sensitivity and specificity values and moderate agreement in terms of the Kappa statistic. These results were similar for vertical axis and vector magnitude cut-off points. The current cut-off points adequately reflect MVPA and VPA in young children. Cut-off points based on vector magnitude counts did not appear to reflect the intensity categories better than cut-off points based on vertical axis counts alone.