Online tracking of the phase difference between neural drives to antagonist muscle pairs in essential tremor patients

Transcutaneous electrical stimulation has been applied in tremor suppression applications. Out-of-phase stimulation strategies applied above or below motor threshold result in a significant attenuation of pathological tremor. For stimulation to be properly timed, the varying phase relationship between agonist-antagonist muscle activity during tremor needs to be accurately estimated in real-time. Here we propose an online tremor phase and frequency tracking technique for the customized control of electrical stimulation, based on a phase-locked loop (PLL) system applied to the estimated neural drive to muscles. Surface electromyography signals were recorded from the wrist extensor and flexor muscle groups of 13 essential tremor patients during postural tremor. The EMG signals were pre-processed and decomposed online and offline via the convolution kernel compensation algorithm to discriminate motor unit spike trains. The summation of motor unit spike trains detected for each muscle was bandpass filtered between 3 to 10 Hz to isolate the tremor related components of the neural drive to muscles. The estimated tremorogenic neural drive was used as input to a PLL that tracked the phase differences between the two muscle groups. The online estimated phase difference was compared with the phase calculated offline using a Hilbert Transform as a ground truth. The results showed a rate of agreement of 0.88 ± 0.22 between offline and online EMG decomposition. The PLL tracked the phase difference of tremor signals in real-time with an average correlation of 0.86 ± 0.16 with the ground truth (average error of 6.40° ± 3.49°). Finally, the online decomposition and phase estimation components were integrated with an electrical stimulator and applied in closed-loop on one patient, to representatively demonstrate the working principle of the full tremor suppression system. The results of this study support the feasibility of real-time estimation of the phase of tremorogenic neural drive to muscles, providing a methodology for future tremor-suppression neuroprostheses

New Physics in b -> s mu+ mu-: CP-Conserving Observables

We perform a comprehensive study of the impact of new-physics operators with different Lorentz structures on decays involving the b -> s mu+ mu- transition. We examine the effects of new vector-axial vector (VA), scalar-pseudoscalar (SP) and tensor (T) interactions on the differential branching ratios and forward-backward asymmetries (A_{FB}'s) of Bsbar -> mu+ mu-, Bdbar -> Xs mu+ mu-, Bsbar -> mu+ mu- gamma, Bdbar -> Kbar mu+ mu-, and Bdbar -> K* mu+ mu-, taking the new-physics couplings to be real. In Bdbar -> K* mu+ mu-, we further explore the polarization fraction f_L, the angular asymmetry A_T^{(2)}, and the longitudinal-transverse asymmetry A_{LT}. We identify the Lorentz structures that would significantly impact these observables, providing analytical arguments in terms of the contributions from the individual operators and their interference terms. In particular, we show that while the new VA operators can significantly enhance most of the asymmetries beyond the Standard Model predictions, the SP and T operators can do this only for A_{FB} in Bdbar -> Kbar mu+ mu-.Comment: 54 pages, JHEP format, 45 figures (included). 5/6/2013: typos in K* mu mu angular coefficients corrected, typos in Eq. (D.12) corrected, added a missing term in I3LT in Eq. (D.16). Numerical analysis unchange

New-physics contributions to the forward-backward asymmetry in B -> K* mu+ mu-

We study the forward-backward asymmetry (AFB) and the differential branching ratio (DBR) in B -> K* mu+ mu- in the presence of new physics (NP) with different Lorentz structures. We consider NP contributions from vector-axial vector (VA), scalar-pseudoscalar (SP), and tensor (T) operators, as well as their combinations. We calculate the effects of these new Lorentz structures in the low-q^2 and high-q^2 regions, and explain their features through analytic approximations. We find two mechanisms that can give a significant deviation from the standard-model predictions, in the direction indicated by the recent measurement of AFB by the Belle experiment. They involve the addition of the following NP operators: (i) VA, or (ii) a combination of SP and T (slightly better than T alone). These two mechanisms can be distinguished through measurements of DBR in B -> K* mu+ mu- and AFB in B -> K mu+ mu-.Comment: 33 pages, revtex, 9 figures. Paper originally submitted with the wrong figures. This is corrected in the replacement. An incorrect factor of 2 found in a formula. This is corrected and figures modified. Conclusions unchanged. Typos correcte

Timing and documentation of key events in neonatal resuscitation

Only a minority of babies require extended resuscitation at birth. Resuscitations concerning babies who die or who survive with adverse outcomes are increasingly subject to medicolegal scrutiny. Our aim was to describe real-life timings of key resuscitation events observed in a historical series of newborns who required full resuscitation at birth. Twenty-seven babies born in our centre over a 10-year period had an Apgar score of 0 at 1 min and required full resuscitation. The median (95% confidence interval) postnatal age at achieving key events were commencing cardiac compressions, 2.0 (1.5–4.0) min; endotracheal intubation, 3.8 (2.0–6.0) min; umbilical venous catheterisation 9.0 (7.5–12.0) min; and administration of first adrenaline dose 10.0 (8.0–14.0) min. Conclusion: The wide range of timings presented from real-life cases may prove useful to clinicians involved in medical negligence claims and provide a baseline for quality improvements in resuscitation training

Supersymmetric constraints from Bs -> mu+mu- and B -> K* mu+mu- observables

We study the implications of the recent LHCb limit and results on Bs -> mu+mu- and B -> K* mu+mu- observables in the constrained SUSY scenarios. After discussing the Standard Model predictions and carefully estimating the theoretical errors, we show the constraining power of these observables in CMSSM and NUHM. The latest limit on BR(Bs -> mu+mu-), being very close to the SM prediction, constrains strongly the large tan(beta) regime and we show that the various angular observables from B -> K* mu+mu- decay can provide complementary information in particular for moderate tan(beta) values.Comment: 30 pages, 14 figure

The use of happiness research for public policy

Research on happiness tends to follow a "benevolent dictator" approach where politicians pursue people's happiness. This paper takes an antithetic approach based on the insights of public choice theory. First, we inquire how the results of happiness research may be used to improve the choice of institutions. Second, we show that the policy approach matters for the choice of research questions and the kind of knowledge happiness research aims to provide. Third, we emphasize that there is no shortcut to an optimal policy maximizing some happiness indicator or social welfare function since governments have an incentive to manipulate this indicator

SPH Simulations of Negative (Nodal) Superhumps: A Parametric Study

Negative superhumps in cataclysmic variable systems result when the accretion disc is tilted with respect to the orbital plane. The line of nodes of the tilted disc precesses slowly in the retrograde direction, resulting in a photometric signal with a period slightly less than the orbital period. We use the method of smoothed particle hydrodynamics to simulate a series of models of differing mass ratio and effective viscosity to determine the retrograde precession period and superhump period deficit $\varepsilon_-$ as a function of system mass ratio $q$. We tabulate our results and present fits to both $\varepsilon_-$ and $\varepsilon_+$ versus $q$, as well as compare the numerical results with those compiled from the literature of negative superhump observations. One surprising is that while we find negative superhumps most clearly in simulations with an accretion stream present, we also find evidence for negative superhumps in simulations in which we shut off the mass transfer stream completely, indicating that the origin of the photometric signal is more complicated than previously believed.Comment: 14 pages, 15 figures. Accepted for publication in MNRA

Exploring New Physics in the C7-C7' plane

The Wilson coefficient C7 governing the radiative electromagnetic decays of B meson has been calculated to a very high accuracy in the Standard Model, but experimental bounds on either the magnitude or the sign of C7 are often model-dependent. In the present paper, we attempt at constraining both the magnitude and sign of C7 using a systematic approach. We consider already measured observables like the branching ratios of B \rightarrow Xs mu+ mu- and B \rightarrow Xs gamma, the isospin and CP asymmetries in B \rightarrow K* gamma, as well as AFB and FL in B \rightarrow K*l+l-. We also discuss the transverse observable AT2 which, once measured, may help to disentangle some of the scenarios considered. We explore the constraints on C7, C9, C10 as well as their chirality-flipped counterparts. Within our framework, we find that we need to extend the constraints up to 1.6 sigma to allow for the "flipped-sign solution" of C7. The SM solution for C7 exhibits a very mild tension if New Physics is allowed in dipole operators only. We provide semi-numerical expressions for all these observables as functions of the relevant Wilson coefficients at the low scale.Comment: 54 pages, 16 figures, 15 tables. Normalization factor introduced for the integrated AFB and FL in Sec.2.5 (Eq.2.35-2.38). Conclusions unchanged. Not updated in JHE

Perturbation with Intrabodies Reveals That Calpain Cleavage Is Required for Degradation of Huntingtin Exon 1

Background: Proteolytic processing of mutant huntingtin (mHtt), the protein that causes Huntington's disease (HD), is critical for mHtt toxicity and disease progression. mHtt contains several caspase and calpain cleavage sites that generate N-terminal fragments that are more toxic than full-length mHtt. Further processing is then required for the degradation of these fragments, which in turn, reduces toxicity. This unknown, secondary degradative process represents a promising therapeutic target for HD. Methodology/Principal Findings: We have used intrabodies, intracellularly expressed antibody fragments, to gain insight into the mechanism of mutant huntingtin exon 1 (mHDx-1) clearance. Happ1, an intrabody recognizing the proline-rich region of mHDx-1, reduces the level of soluble mHDx-1 by increasing clearance. While proteasome and macroautophagy inhibitors reduce turnover of mHDx-1, Happ1 is still able to reduce mHDx-1 under these conditions, indicating Happ1-accelerated mHDx-1 clearance does not rely on these processes. In contrast, a calpain inhibitor or an inhibitor of lysosomal pH block Happ1-mediated acceleration of mHDx-1 clearance. These results suggest that mHDx-1 is cleaved by calpain, likely followed by lysosomal degradation and this process regulates the turnover rate of mHDx-1. Sequence analysis identifies amino acid (AA) 15 as a potential calpain cleavage site. Calpain cleavage of recombinant mHDx-1 in vitro yields fragments of sizes corresponding to this prediction. Moreover, when the site is blocked by binding of another intrabody, V_L12.3, turnover of soluble mHDx-1 in living cells is blocked. Conclusions/Significance: These results indicate that calpain-mediated removal of the 15 N-terminal AAs is required for the degradation of mHDx-1, a finding that may have therapeutic implications