Deep brain electrical neurofeedback allows Parkinson patients to control pathological oscillations and quicken movements

Parkinsonian motor symptoms are linked to pathologically increased beta-oscillations in the basal ganglia. While pharmacological treatment and deep brain stimulation (DBS) reduce these pathological oscillations concomitantly with improving motor performance, we set out to explore neurofeedback as an endogenous modulatory method. We implemented real-time processing of pathological subthalamic beta oscillations through implanted DBS electrodes to provide deep brain electrical neurofeedback. Patients volitionally controlled ongoing beta-oscillatory activity by visual neurofeedback within minutes of training. During a single one-hour training session, the reduction of beta-oscillatory activity became gradually stronger and we observed improved motor performance. Lastly, endogenous control over deep brain activity was possible even after removing visual neurofeedback, suggesting that neurofeedback-acquired strategies were retained in the short-term. Moreover, we observed motor improvement when the learnt mental strategies were applied 2 days later without neurofeedback. Further training of deep brain neurofeedback might provide therapeutic benefits for Parkinson patients by improving symptom control using strategies optimized through neurofeedback

Visualizing alpha-synuclein and iron deposition in M83 mouse model of Parkinson's disease in vivo

BACKGROUND Abnormal alpha-synuclein and iron accumulation in the brain play an important role in Parkinson's disease (PD). Herein, we aim at visualizing alpha-synuclein inclusions and iron deposition in the brains of M83 (A53T) mouse models of PD in vivo . METHODS Fluorescently labelled pyrimidoindole-derivative THK-565 was characterized by using recombinant fibrils and brains from 10-11 months old M83 mice, which subsequently underwent in vivo concurrent wide-field fluorescence and volumetric multispectral optoacoustic tomography (vMSOT) imaging. The in vivo results were verified against structural and susceptibility weighted imaging (SWI) magnetic resonance imaging (MRI) at 9.4 Tesla and scanning transmission X-ray microscopy (STXM) of perfused brains. Brain slice immunofluorescence and Prussian blue staining were further performed to validate the detection of alpha-synuclein inclusions and iron deposition in the brain, respectively. RESULTS THK-565 showed increased fluorescence upon binding to recombinant alpha-synuclein fibrils and alpha-synuclein inclusions in post-mortem brain slices from patients with Parkinson's disease and M83 mice. i.v. administration of THK-565 in M83 mice showed higher cerebral retention at 20 and 40 minutes post-injection by wide-field fluorescence compared to non-transgenic littermate mice, in congruence with the vMSOT findings. SWI/phase images and Prussian blue indicated the accumulation of iron deposits in the brains of M83 mice, presumably in the Fe $^{3+}$ form, as evinced by the STXM results. CONCLUSION We demonstrated in vivo mapping of alpha-synuclein by means of non-invasive epifluorescence and vMSOT imaging assisted with a targeted THK-565 label and SWI/STXM identification of iron deposits in M83 mouse brains ex vivo

Search for Higgs Bosons in e+e- Collisions at 183 GeV

The data collected by the OPAL experiment at sqrts=183 GeV were used to search for Higgs bosons which are predicted by the Standard Model and various extensions, such as general models with two Higgs field doublets and the Minimal Supersymmetric Standard Model (MSSM). The data correspond to an integrated luminosity of approximately 54pb-1. None of the searches for neutral and charged Higgs bosons have revealed an excess of events beyond the expected background. This negative outcome, in combination with similar results from searches at lower energies, leads to new limits for the Higgs boson masses and other model parameters. In particular, the 95% confidence level lower limit for the mass of the Standard Model Higgs boson is 88.3 GeV. Charged Higgs bosons can be excluded for masses up to 59.5 GeV. In the MSSM, mh > 70.5 GeV and mA > 72.0 GeV are obtained for tan{beta}>1, no and maximal scalar top mixing and soft SUSY-breaking masses of 1 TeV. The range 0.8 < tanb < 1.9 is excluded for minimal scalar top mixing and m{top} < 175 GeV. More general scans of the MSSM parameter space are also considered.Comment: 49 pages. LaTeX, including 33 eps figures, submitted to European Physical Journal

A Measurement of the Product Branching Ratio f(b->Lambda_b).BR(Lambda_b->Lambda X) in Z0 Decays

The product branching ratio, f(b->Lambda_b).BR(Lambda_b->Lambda X), where Lambda_b denotes any weakly-decaying b-baryon, has been measured using the OPAL detector at LEP. Lambda_b are selected by the presence of energetic Lambda particles in bottom events tagged by the presence of displaced secondary vertices. A fit to the momenta of the Lambda particles separates signal from B meson and fragmentation backgrounds. The measured product branching ratio is f(b->Lambda_b).BR(Lambda_b->Lambda X) = (2.67+-0.38(stat)+0.67-0.60(sys))% Combined with a previous OPAL measurement, one obtains f(b->Lambda_b).BR(Lambda_b->Lambda X) = (3.50+-0.32(stat)+-0.35(sys))%.Comment: 16 pages, LaTeX, 3 eps figs included, submitted to the European Physical Journal

Measurement of the Michel Parameters in Leptonic Tau Decays

The Michel parameters of the leptonic tau decays are measured using the OPAL detector at LEP. The Michel parameters are extracted from the energy spectra of the charged decay leptons and from their energy-energy correlations. A new method involving a global likelihood fit of Monte Carlo generated events with complete detector simulation and background treatment has been applied to the data recorded at center-of-mass energies close to sqrt(s) = M(Z) corresponding to an integrated luminosity of 155 pb-1 during the years 1990 to 1995. If e-mu universality is assumed and inferring the tau polarization from neutral current data, the measured Michel parameters are extracted. Limits on non-standard coupling constants and on the masses of new gauge bosons are obtained. The results are in agreement with the V-A prediction of the Standard Model.Comment: 32 pages, LaTeX, 9 eps figures included, submitted to the European Physical Journal

Targeting Huntingtin expression in patients with Huntington's disease

Background Huntington’s disease is an autosomal-dominant neurodegenerative disease caused by CAG trinucleotide repeat expansion in HTT, resulting in a mutant huntingtin protein. IONIS-HTTRx (hereafter, HTTRx) is an antisense oligonucleotide designed to inhibit HTT messenger RNA and thereby reduce concentrations of mutant huntingtin. Methods We conducted a randomized, double-blind, multiple-ascending-dose, phase 1–2a trial involving adults with early Huntington’s disease. Patients were randomly assigned in a 3:1 ratio to receive HTTRx or placebo as a bolus intrathecal administration every 4 weeks for four doses. Dose selection was guided by a preclinical model in mice and nonhuman primates that related dose level to reduction in the concentration of huntingtin. The primary end point was safety. The secondary end point was HTTRx pharmacokinetics in cerebrospinal fluid (CSF). Prespecified exploratory end points included the concentration of mutant huntingtin in CSF. Results Of the 46 patients who were enrolled in the trial, 34 were randomly assigned to receive HTTRx (at ascending dose levels of 10 to 120 mg) and 12 were randomly assigned to receive placebo. Each patient received all four doses and completed the trial. Adverse events, all of grade 1 or 2, were reported in 98% of the patients. No serious adverse events were seen in HTTRx-treated patients. There were no clinically relevant adverse changes in laboratory variables. Predose (trough) concentrations of HTTRx in CSF showed dose dependence up to doses of 60 mg. HTTRx treatment resulted in a dose-dependent reduction in the concentration of mutant huntingtin in CSF (mean percentage change from baseline, 10% in the placebo group and −20%, −25%, −28%, −42%, and −38% in the HTTRx 10-mg, 30-mg, 60-mg, 90-mg, and 120-mg dose groups, respectively). Conclusions Intrathecal administration of HTTRx to patients with early Huntington’s disease was not accompanied by serious adverse events. We observed dose-dependent reductions in concentrations of mutant huntingtin. (Funded by Ionis Pharmaceuticals and F. Hoffmann–La Roche; ClinicalTrials.gov number, NCT02519036.

Inclusive production of charged hadrons and Ks0K_{s}^{0} mesons in photon-photon collisions

The production of charged hadrons and K_s mesons in the collisions of quasi-real photons has been measured using the OPAL detector at LEP. The data were taken at e+e- centre-of-mass energies of 161 and 172 GeV. The differential cross-sections as a function of the transverse momentum and the pseudorapidity of the charged hadrons and K_s mesons have been compared to the leading order Monte Carlo simulations of PHOJET and PYTHIA and to perturbative next-to-leading order (NLO) QCD calculations. The distributions have been measured in the range 10-125 GeV of the hadronic invariant mass W. By comparing the transverse momentum distribution of charged hadrons measured in gamma-gamma interactions with gamma-proton and meson-proton data we find evidence for hard photon interactions in addition to the purely hadronic photon interactions.The production of charged hadrons and K_s mesons in the collisions of quasi-real photons has been measured using the OPAL detector at LEP. The data were taken at e+e- centre-of-mass energies of 161 and 172 GeV. The differential cross-sections as a function of the transverse momentum and the pseudorapidity of the charged hadrons and K_s mesons have been compared to the leading order Monte Carlo simulations of PHOJET and PYTHIA and to perturbative next-to-leading order (NLO) QCD calculations. The distributions have been measured in the range 10-125 GeV of the hadronic invariant mass W. By comparing the transverse momentum distribution of charged hadrons measured in gamma-gamma interactions with gamma-proton and meson-proton data we find evidence for hard photon interactions in addition to the purely hadronic photon interactions

Measurement of the B+B^{+} and B0B^{0} lifetimes and search for CP(T) violation using reconstructed secondary vertices

The lifetimes of the B+ and B0 mesons, and their ratio, have been measured in the OPAL experiment using 2.4 million hadronic Z0 decays recorded at LEP. Z0 -> b bbar decays were tagged using displaced secondary vertices and high momentum electrons and muons. The lifetimes were then measured using well-reconstructed charged and neutral secondary vertices selected in this tagged data sample. The results are tau(B+) = 1.643 +- 0.037 +- 0.025 ps tau(B0) = 1.523 +- 0.057 +- 0.053 ps ratio tau(B+)/tau(B0) = 1.079 +- 0.064 +- 0.041 where in each case the first error is statistical and the second systematic. A larger data sample of 3.1 million hadronic Z0 decays has been used to search for CP and CPT violating effects by comparison of inclusive b and bbar hadron decays. No evidence for such effects is seen. The CP violation parameter Re(epsilon_B) is measured to be Re(epsilon_B) = 0.001 +- 0.014 +- 0.003 and the fractional difference between b and bbar hadron lifetimes is measured to be -0.001 +- 0.012 +- 0.00

A search for neutral Higgs bosons in the MSSM and models with two scalar field doublets

A search is described for the neutral Higgs bosons h^0 and A^0 predicted by models with two scalar field doublets and, in particular, the Minimal Supersymmetric Standard Model (MSSM). The search in the Z^0 h^0 and h^0 A^0 production channels is based on data corresponding to an integrated luminosity of 25 pb^{-1} from e^+e^- collisions at centre-of-mass energies between 130 and 172GeV collected with the OPAL detector at LEP. The observation of a number of candidates consistent with Standard Model background expectations is used in combination with earlier results from data collected at the Z^0 resonance to set limits on m_h and m_A in general models with two scalar field doublets and in the MSSM. For example, in the MSSM, for tan(beta) > 1, minimal and maximal scalar top quark mixing and soft SUSY-breaking masses of 1 TeV, the 95% confidence level limits m_h > 59.0 GeV and m_A > 59.5 GeV are obtained. For the first time, the MSSM parameter space is explored in a detailed scan.A search is described for the neutral Higgs bosons h^0 and A^0 predicted by models with two scalar field doublets and, in particular, the Minimal Supersymmetric Standard Model (MSSM). The search in the Z^0 h^0 and h^0 A^0 production channels is based on data corresponding to an integrated luminosity of 25 pb^{-1} from e^+e^- collisions at centre-of-mass energies between 130 and 172 GeV collected with the OPAL detector at LEP. The observation of a number of candidates consistent with Standard Model background expectations is used in combination with earlier results from data collected at the Z^0 resonance to set limits on m_h and m_A in general models with two scalar field doublets and in the MSSM. For example, in the MSSM, for tan(beta) > 1, minimal and maximal scalar top quark mixing and soft SUSY-breaking masses of 1 TeV, the 95% confidence level limits m_h > 59.0 GeV and m_A > 59.5 GeV are obtained. For the first time, the MSSM parameter space is explored in a detailed scan