Further evidence for the planet around 51 Pegasi

The discovery of the planet around the solar-type star 51 Pegasi marked a watershed in the search for extrasolar planets. Since then seven other solar-type stars have been discovered, of which several have surprisingly short orbital periods, like the planet around 51 Peg. These planets were detected using the indirect technique of measuring variations in the Doppler shifts of lines in the spectra of the primary stars. But it is possible that oscillations of the stars themselves (or other effects) could mimic the signature of the planets, particularly around the short-period planets. The apparent lack of spectral and brightness variations, however, led to widespread acceptance that there is a planet around 51 Peg. This conclusion was challenged by the observation of systematic variations in the line profile shapes of 51 Peg, which suggested stellar oscillations. If these observations are correct, then there is no need to invoke a planet around 51 Peg to explain the data. Here we report observations of 51 Peg at a much higher spectral resolution than those in ref.9, in which we find no evidence for systematic changes in the line shapes. The data are most consistent with a planetary companion to 51 Peg.Comment: LaTeX, 6 pages, 2 figures. To appear in 8 January 1998 issue of Natur

Frontal white matter tracts sustaining speech production in primary progressive aphasia

In primary progressive aphasia (PPA), speech and language difficulties are caused by neurodegeneration of specific brain networks. In the nonfluent/agrammatic variant (nfvPPA), motor speech and grammatical deficits are associated with atrophy in a left fronto-insular-striatal network previously implicated in speech production. In vivo dissection of the crossing white matter (WM) tracts within this "speech production network" is complex and has rarely been performed in health or in PPA. We hypothesized that damage to these tracts would be specific to nfvPPA and would correlate with differential aspects of the patients' fluency abilities. We prospectively studied 25 PPA and 21 healthy individuals who underwent extensive cognitive testing and 3 T MRI. Using residual bootstrap Q-ball probabilistic tractography on high angular resolution diffusion-weighted imaging (HARDI), we reconstructed pathways connecting posterior inferior frontal, inferior premotor, insula, supplementary motor area (SMA) complex, striatum, and standard ventral and dorsal language pathways. We extracted tract-specific diffusion tensor imaging (DTI) metrics to assess changes across PPA variants and perform brain-behavioral correlations. Significant WM changes in the left intrafrontal and frontostriatal pathways were found in nfvPPA, but not in the semantic or logopenic variants. Correlations between tract-specific DTI metrics with cognitive scores confirmed the specific involvement of this anterior-dorsal network in fluency and suggested a preferential role of a posterior premotor-SMA pathway in motor speech. This study shows that left WM pathways connecting the speech production network are selectively damaged in nfvPPA and suggests that different tracts within this system are involved in subcomponents of fluency. These findings emphasize the emerging role of diffusion imaging in the differential diagnosis of neurodegenerative diseases

The formation of a novel free radical metabolite from CCl4 in the perfused rat liver and in vivo.

Electron spin resonance spectroscopy has been used to monitor free radicals formed during CCl4 metabolism by perfused livers from phenobarbital-treated rats. Livers were perfused simultaneously with the spin trap phenyl N-t-butylnitrone and with either 12CCl4 or 13CCl4. Perfusate samples and CHCl3:CH3OH extracts of perfusate and liver samples were analyzed for phenyl N-t-butylnitrone radical adducts of reactive free radicals. In the organic extracts, hyperfine coupling constants and 13C isotope effects observed in the ESR spectra indicated the presence of the radical adduct of the trichloromethyl radical. Surprisingly, an additional free radical signal about two orders of magnitude more intense than that of the phenyl N-t-butylnitrone/CCl.3 radical adduct was observed in the aqueous liver perfusate. This adduct was also detected by ESR in rat urine 2 h after intragastric addition of spin trap and CCl4. This radical adduct had hyperfine coupling constants and 13C isotope effects identical with the radical adduct of the carbon dioxide anion radical (CO2-.). Analysis of the pH dependence of the coupling constants yielded a pK alpha of 2.8 for the CO2-. radical adduct formed either in the perfused liver or chemically. Carbon tetrachloride is converted into CCl.3 by cytochrome P-450 through a reductive dehalogenation. The trichloromethyl free radical reacts with oxygen to form the trichloromethyl peroxyl radical, CCl3OO., which may be converted into .COCl and then trapped. This radical adduct would hydrolyze to the carboxylic acid form, which is detected spectroscopically. Alternatively, the carbon dioxide anion free radical could form through complete dechlorination and then react with the spin trap to give the CO2-. radical adduct directly

Neurite Orientation Dispersion and Density Imaging Color Maps to Characterize Brain Diffusion in Neurologic Disorders

Purpose: Neurite orientation dispersion and density imaging (NODDI) has recently been developed to overcome diffusion technique limitations in modeling biological systems. This manuscript reports a preliminary investigation into the use of a single color-coded map to represent NODDI-derived information. Materials and methods: An optimized diffusion-weighted imaging protocol was acquired in several clinical neurological contexts including demyelinating disease, neoplastic process, stroke, and toxic/metabolic disease. The NODDI model was fitted to the diffusion datasets. NODDI is based on a three-compartment diffusion model and provides maps that quantify the contributions to the total diffusion signal in each voxel. The NODDI compartment maps were combined into a single 4-dimensional volume visualized as RGB image (red for anisotropic Gaussian diffusion, green for non-Gaussian anisotropic diffusion, and blue for isotropic Gaussian diffusion), in which the relative contributions of the different microstructural compartments can be easily appreciated. Results: The NODDI color maps better describe the heterogeneity of neoplastic as well inflammatory lesions by identifying different tissue components within areas apparently homogeneous on conventional imaging. Moreover, NODDI color maps seem to be useful for identifying vasogenic edema differently from tumor-infiltrated edema. In multiple sclerosis, the NODDI color maps enable a visual assessment of the underlying microstructural changes, possibly highlighting an increased inflammatory component, within lesions and potentially in normal-appearing white matter. Conclusion: The NODDI color maps could make this technique valuable in a clinical setting, providing comprehensive and accessible information in normal and pathological brain tissues in different neurological pathologies

52-week efficacy and safety of telbivudine with conditional tenofovir intensification at week 24 in HBeAg-positive chronic Hepatitis B

Background and Aims: The Roadmap concept is a therapeutic framework in chronic hepatitis B for the intensification of nucleoside analogue monotherapy based on early virologic response. The efficacy and safety of this approach applied to telbivudine treatment has not been investigated. Methods: A multinational, phase IV, single-arm open-label study (ClinicalTrials.gov ID NCT00651209) was undertaken in HBeAg-positive, nucleoside-naive adult patients with chronic hepatitis B. Patients received telbivudine (600 mg once-daily) for 24 weeks, after which those with undetectable serum HBV DNA (<300 copies/mL) continued to receive telbivudine alone while those with detectable DNA received telbivudine plus tenofovir (300 mg once-daily). Outcomes were assessed at Week 52. Results: 105 patients commenced telbivudine monotherapy, of whom 100 were included in the efficacy analysis. Fifty-five (55%) had undetectable HBV DNA at Week 24 and continued telbivudine monotherapy; 45 (45%) received tenofovir intensification. At Week 52, the overall proportion of undetectable HBV DNA was 93% (93/100) by last-observation-carried-forward analysis (100% monotherapy group, 84% intensification group) and no virologic breakthroughs had occurred. ALT normalization occurred in 77% (87% monotherapy, 64% intensification), HBeAg clearance in 43% (65% monotherapy, 16% intensification), and HBeAg seroconversion in 39% (62% monotherapy, 11% intensification). Six patients had HBsAg clearance. Myalgia was more common in the monotherapy group (19% versus 7%). No decrease in the mean glomerular filtration rate occurred in either treatment group at Week 52. Conclusions: Telbivudine therapy with tenofovir intensification at Week 24, where indicated by the Roadmap strategy, appears effective and well tolerated for the treatment of chronic hepatitis B. Trial Registration: ClinicalTrials.gov NCT0065120

Use of low-dose oral theophylline as an adjunct to inhaled corticosteroids in preventing exacerbations of chronic obstructive pulmonary disease: study protocol for a randomised controlled trial.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with high morbidity, mortality, and health-care costs. An incomplete response to the anti-inflammatory effects of inhaled corticosteroids is present in COPD. Preclinical work indicates that 'low dose' theophylline improves steroid responsiveness. The Theophylline With Inhaled Corticosteroids (TWICS) trial investigates whether the addition of 'low dose' theophylline to inhaled corticosteroids has clinical and cost-effective benefits in COPD. METHOD/DESIGN: TWICS is a randomised double-blind placebo-controlled trial conducted in primary and secondary care sites in the UK. The inclusion criteria are the following: an established predominant respiratory diagnosis of COPD (post-bronchodilator forced expiratory volume in first second/forced vital capacity [FEV1/FVC] of less than 0.7), age of at least 40 years, smoking history of at least 10 pack-years, current inhaled corticosteroid use, and history of at least two exacerbations requiring treatment with antibiotics or oral corticosteroids in the previous year. A computerised randomisation system will stratify 1424 participants by region and recruitment setting (primary and secondary) and then randomly assign with equal probability to intervention or control arms. Participants will receive either 'low dose' theophylline (Uniphyllin MR 200 mg tablets) or placebo for 52 weeks. Dosing is based on pharmacokinetic modelling to achieve a steady-state serum theophylline of 1-5 mg/l. A dose of theophylline MR 200 mg once daily (or placebo once daily) will be taken by participants who do not smoke or participants who smoke but have an ideal body weight (IBW) of not more than 60 kg. A dose of theophylline MR 200 mg twice daily (or placebo twice daily) will be taken by participants who smoke and have an IBW of more than 60 kg. Participants will be reviewed at recruitment and after 6 and 12 months. The primary outcome is the total number of participant-reported COPD exacerbations requiring oral corticosteroids or antibiotics during the 52-week treatment period. DISCUSSION: The demonstration that 'low dose' theophylline increases the efficacy of inhaled corticosteroids in COPD by reducing the incidence of exacerbations is relevant not only to patients and clinicians but also to health-care providers, both in the UK and globally. TRIAL REGISTRATION: Current Controlled Trials ISRCTN27066620 was registered on Sept. 19, 2013, and the first subject was randomly assigned on Feb. 6, 2014

Inhalation of the Rho-kinase inhibitor Y-27632 reverses allergen-induced airway hyperresponsiveness after the early and late asthmatic reaction

BACKGROUND: In guinea pigs, we have previously demonstrated that the contribution of Rho-kinase to airway responsiveness in vivo and ex vivo is enhanced after active sensitization with ovalbumin (OA). Using conscious, unrestrained OA-sensitized guina pigs, we now investigated the role of Rho-kinase in the development of airway hyperresponsiveness (AHR) after the allergen-induced early (EAR) and late asthmatic reaction (LAR) in vivo. METHODS: Histamine and PGF(2α )PC(100)-values (provocation concentrations causing 100% increase in pleural pressure) were assessed before OA-challenge (basal airway responsiveness) and after the OA-induced EAR (5 h after challenge) and LAR (23 h after challenge). Thirty minutes later, saline or the specific Rho-kinase inhibitor Y-27632 (5 mM, nebulizer concentration) were nebulized, after which PC(100)-values were reassessed. RESULTS: In contrast to saline, Y-27632 inhalation significantly decreased the basal responsiveness toward histamine and PGF(2α )before OA-challenge, as indicated by increased PC(100 )-values. Both after the allergen-induced EAR and LAR, AHR to histamine and PGF(2α )was present, which was reversed by Y-27632 inhalation. Moreover, there was an increased effectiveness of Y-27632 to reduce airway responsiveness to histamine and PGF(2α )after the EAR and LAR as compared to pre-challenge conditions. Saline inhalations did not affect histamine or PGF(2α )PC(100)-values at all. Interestingly, under all conditions Y-27632 was significantly more effective in reducing airway responsiveness to PGF(2α )as compared to histamine. Also, there was a clear tendency (P = 0.08) to a more pronounced degree of AHR after the EAR for PGF(2α )than for histamine. CONCLUSION: The results indicate that inhalation of the Rho-kinase inhibitor Y-27632 causes a considerable bronchoprotection to both histamine and PGF(2α). Moreover, the results are indicative of a differential involvement of Rho-kinase in the agonist-induced airway obstruction in vivo. Increased Rho-kinase activity contributes to the allergen-induced AHR to histamine and PGF(2α )after both the EAR and the LAR, which is effectively reversed by inhalation of Y-27632. Therefore, Rho-kinase can be considered as a potential pharmacotherapeutical target in allergic asthma

Prevalence of Grey Matter Pathology in Early Multiple Sclerosis Assessed by Magnetization Transfer Ratio Imaging

The aim of the study was to assess the prevalence, the distribution and the impact on disability of grey matter (GM) pathology in early multiple sclerosis. Eighty-eight patients with a clinically isolated syndrome with a high risk developing multiple sclerosis were included in the study. Forty-four healthy controls constituted the normative population. An optimized statistical mapping analysis was performed to compare each subject's GM Magnetization Transfer Ratio (MTR) imaging maps with those of the whole group of controls. The statistical threshold of significant GM MTR decrease was determined as the maximum p value (p<0.05 FDR) for which no significant cluster survived when comparing each control to the whole control population. Using this threshold, 51% of patients showed GM abnormalities compared to controls. Locally, 37% of patients presented abnormalities inside the limbic cortex, 34% in the temporal cortex, 32% in the deep grey matter, 30% in the cerebellum, 30% in the frontal cortex, 26% in the occipital cortex and 19% in the parietal cortex. Stepwise regression analysis evidenced significant association (p = 0.002) between EDSS and both GM pathology (p = 0.028) and T2 white matter lesions load (p = 0.019). In the present study, we evidenced that individual analysis of GM MTR map allowed demonstrating that GM pathology is highly heterogeneous across patients at the early stage of MS and partly underlies irreversible disability

Barcoding Bugs: DNA-Based Identification of the True Bugs (Insecta: Hemiptera: Heteroptera)

oxidase I (COI) gene, has been shown to provide an efficient method for the identification of species in a wide range of animal taxa. In order to assess the effectiveness of barcodes in the discrimination of Heteroptera, we examined 344 species belonging to 178 genera, drawn from specimens in the Canadian National Collection of Insects.Analysis of the COI gene revealed less than 2% intra-specific divergence in 90% of the taxa examined, while minimum interspecific distances exceeded 3% in 77% of congeneric species pairs. Instances where barcodes fail to distinguish species represented clusters of morphologically similar species, except one case of barcode identity between species in different genera. Several instances of deep intraspecific divergence were detected suggesting possible cryptic species.Although this analysis encompasses 0.8% of the described global fauna, our results indicate that DNA barcodes will aid the identification of Heteroptera. This advance will be useful in pest management, regulatory and environmental applications and will also reveal species that require further taxonomic research