Comment on "Including Systematic Uncertainties in Confidence Interval Construction for Poisson Statistics"

The incorporation of systematic uncertainties into confidence interval calculations has been addressed recently in a paper by Conrad et al. (Physical Review D 67 (2003) 012002). In their work, systematic uncertainities in detector efficiencies and background flux predictions were incorporated following the hybrid frequentist-Bayesian prescription of Cousins and Highland, but using the likelihood ratio ordering of Feldman and Cousins in order to produce "unified" confidence intervals. In general, the resulting intervals behaved as one would intuitively expect, i.e. increased with increasing uncertainties. However, it was noted that for numbers of observed events less than or of order of the expected background, the intervals could sometimes behave in a completely counter-intuitive fashion -- being seen to initially decrease in the face of increasing uncertainties, but only for the case of increasing signal efficiency uncertainty. In this comment, we show that the problematic behaviour is due to integration over the signal efficiency uncertainty while maximising the best fit alternative hypothesis likelihood. If the alternative hypothesis likelihood is determined by unconditionally maximising with respect to both the unknown signal and signal efficiency uncertainty, the limits display the correct intuitive behaviour.Comment: Submitted to Physical Review

A Kinetic Alfven wave cascade subject to collisionless damping cannot reach electron scales in the solar wind at 1 AU

(Abridged) Turbulence in the solar wind is believed to generate an energy cascade that is supported primarily by Alfv\'en waves or Alfv\'enic fluctuations at MHD scales and by kinetic Alfv\'en waves (KAWs) at kinetic scales $k_\perp \rho_i\gtrsim 1$. Linear Landau damping of KAWs increases with increasing wavenumber and at some point the damping becomes so strong that the energy cascade is completely dissipated. A model of the energy cascade process that includes the effects of linear collisionless damping of KAWs and the associated compounding of this damping throughout the cascade process is used to determine the wavenumber where the energy cascade terminates. It is found that this wavenumber occurs approximately when $|\gamma/\omega|\simeq 0.25$, where $\omega(k)$ and $\gamma(k)$ are, respectively, the real frequency and damping rate of KAWs and the ratio $\gamma/\omega$ is evaluated in the limit as the propagation angle approaches 90 degrees relative to the direction of the mean magnetic field.Comment: Submitted to Ap

Unified approach to the classical statistical analysis of small signals

We give a classical confidence belt construction which unifies the treatment of upper confidence limits for null results and two-sided confidence intervals for non-null results. The unified treatment solves a problem (apparently not previously recognized) that the choice of upper limit or two-sided intervals leads to intervals which are not confidence intervals if the choice is based on the data. We apply the construction to two related problems which have recently been a battle-ground between classical and Bayesian statistics: Poisson processes with background, and Gaussian errors with a bounded physical region. In contrast with the usual classical construction for upper limits, our construction avoids unphysical confidence intervals. In contrast with some popular Bayesian intervals, our intervals eliminate conservatism (frequentist coverage greater than the stated confidence) in the Gaussian case and reduce it to a level dictated by discreteness in the Poisson case. We generalize the method in order to apply it to analysis of experiments searching for neutrino oscillations. We show that this technique both gives correct coverage and is powerful, while other classical techniques that have been used by neutrino oscillation search experiments fail one or both of these criteria.Physic

Increased Blood Pressure and Hyperdynamic Cardiovascular Responses in Carriers of a Common Hyperfunctional Variant of Adenylyl Cyclase 6

ABSTRACT Adenylyl cyclase (ADCY) is a critical regulator of metabolic and cardiovascular function. We have identified a genetic variant (A674S) in ADCY isoform 6 (ADCY6). Subsequent studies demonstrated that the expression of this ADCY6 variant paralleled an increase in adenylyl cyclase-mediated functions. However, the impact of this hyperfunctional variant on cardiovascular function is unknown. Therefore, we evaluated the hemodynamic profile of carriers of ADCY6 A674S. The association of ADCY6 A674S with anthropometric and hemodynamic parameters was assessed in 364 healthy white subjects. The allele encoding this variant was present in 6.9% of the subjects, and those individuals had increased blood pressure. To determine the hemodynamic basis for increased blood pressure in carriers of ADCY6 A674S, we assessed forearm blood flow (FBF) and cardiac output at rest, during handgrip exercise (to test vasodilator responsiveness), and with lower body negative pressure [to test forearm vasoconstrictor and heart rate (HR) responsiveness] in a subsample of 21 subjects. At rest, cardiac output and blood pressure were higher in carriers of ADCY6 A674S. This was paralleled by an increase in plasma renin activity, but not in plasma norepinephrine. During handgrip exercise, FBF and vasodilator responses were greater in carriers of ADCY6 A674S. Responses to reactive hyperemia were not different between genotypes. With lower body negative pressure, the HR response to this orthostatic stress was markedly higher in carriers of ADCY6 A674S. These data indicate that the relatively common hyperfunctional ADCY6 A674S variant underlies a hyperdynamic cardiovascular response and increased blood pressure

The Acidic Tail of the Cdc34 Ubiquitin-conjugating Enzyme Functions in Both Binding to and Catalysis with Ubiquitin Ligase SCFC^(dc4*)

Ubiquitin ligases, together with their cognate ubiquitin-conjugating enzymes, are responsible for the ubiquitylation of proteins, a process that regulates a myriad of eukaryotic cellular functions. The first cullin-RING ligase discovered, yeast SCF^(Cdc4), functions with the conjugating enzyme Cdc34 to regulate the cell cycle. Cdc34 orthologs are notable for their highly acidic C-terminal extension. Here we confirm that the Cdc34 acidic C-terminal tail has a role in Cdc34 binding to SCF^(Cdc4) and makes a major contribution to the submicromolar K_m of Cdc34 for SCF^(Cdc4). Moreover, we demonstrate that a key functional property of the tail is its acidity. Our analysis also uncovers an unexpected new function for the acidic tail in promoting catalysis. We demonstrate that SCF is functional when Cdc34 is fused to the C terminus of Cul1 and that this fusion retains partial function even when the acidic tail has been deleted. The Cdc34-SCF fusion proteins that lack the acidic tail must interact in a fundamentally different manner than unfused SCF and wild type Cdc34, demonstrating that distinct mechanisms of E2 recruitment to E3, as is seen in nature, can sustain substrate ubiquitylation. Finally, a search of the yeast proteome uncovered scores of proteins containing highly acidic stretches of amino acids, hinting that electrostatic interactions may be a common mechanism for facilitating protein assembly

A Statistical Study on Photospheric Magnetic Nonpotentiality of Active Regions and Its Relationship with Flares during Solar Cycles 22-23

A statistical study is carried out on the photospheric magnetic nonpotentiality in solar active regions and its relationship with associated flares. We select 2173 photospheric vector magnetograms from 1106 active regions observed by the Solar Magnetic Field Telescope at Huairou Solar Observing Station, National Astronomical Observatories of China, in the period of 1988-2008, which covers most of the 22nd and 23rd solar cycles. We have computed the mean planar magnetic shear angle (\bar{\Delta\phi}), mean shear angle of the vector magnetic field (\bar{\Delta\psi}), mean absolute vertical current density (\bar{|J_{z}|}), mean absolute current helicity density (\bar{|h_{c}|}), absolute twist parameter (|\alpha_{av}|), mean free magnetic energy density (\bar{\rho_{free}}), effective distance of the longitudinal magnetic field (d_{E}), and modified effective distance (d_{Em}) of each photospheric vector magnetogram. Parameters \bar{|h_{c}|}, \bar{\rho_{free}}, and d_{Em} show higher correlation with the evolution of the solar cycle. The Pearson linear correlation coefficients between these three parameters and the yearly mean sunspot number are all larger than 0.59. Parameters \bar{\Delta\phi}, \bar{\Delta\psi}, \bar{|J_{z}|}, |\alpha_{av}|, and d_{E} show only weak correlations with the solar cycle, though the nonpotentiality and the complexity of active regions are greater in the activity maximum periods than in the minimum periods. All of the eight parameters show positive correlations with the flare productivity of active regions, and the combination of different nonpotentiality parameters may be effective in predicting the flaring probability of active regions.Comment: 20 pages, 5 figures, 4 tables, accepted for publication in Solar Physic

Suprathermal electron evolution in a Parker spiral magnetic field

Suprathermal electrons (>70 eV) form a small fraction of the total solar wind electron density but serve as valuable tracers of heliospheric magnetic field topology. Their usefulness as tracers of magnetic loops with both feet rooted on the Sun, however, most likely fades as the loops expand beyond some distance owing to scattering. As a first step toward quantifying that distance, we construct an observationally constrained model for the evolution of the suprathermal electron pitch-angle distributions on open field lines. We begin with a near-Sun isotropic distribution moving antisunward along a Parker spiral magnetic field while conserving magnetic moment, resulting in a field-aligned strahl within a few solar radii. Past this point, the distribution undergoes little evolution with heliocentric distance. We then add constant (with heliocentric distance, energy, and pitch angle) ad-hoc pitch-angle scattering. Close to the Sun, pitch-angle focusing still dominates, again resulting in a narrow strahl. Farther from the Sun, however, pitch-angle scattering dominates because focusing is effectively weakened by the increasing angle between the magnetic field direction and intensity gradient, a result of the spiral field. We determine the amount of scattering required to match Ulysses observations of strahl width in the fast solar wind, providing an important tool for inferring the large-scale properties and topologies of field lines in the interplanetary medium. Although the pitch-angle scattering term is independent of energy, time-of-flight effects in the spiral geometry result in an energy dependence of the strahl width that is in the observed sense although weaker in magnitude

Updated recommendations for the management of upper respiratory tract infections in South Africa

Background. Inappropriate use of antibiotics for non-severe upper respiratory tract infections (URTIs), most of which are viral, significantly adds to the burden of antibiotic resistance. Since the introduction of pneumococcal conjugate vaccines in South Africa in 2009, the relative frequency of the major bacterial pathogens causing acute otitis media (AOM) and acute bacterial rhinosinusitis (ABRS) has changed. Recommendations. Since URTIs are mostly viral in aetiology and bacterial AOM and ABRS frequently resolve spontaneously, these recommendations include diagnostic criteria to assist in separating viral from bacterial causes and hence select those patients who do not require antibiotics. Penicillin remains the drug of choice for tonsillopharyngitis and amoxicillin the drug of choice for both AOM and ABRS. A dose of 90 mg/kg/d is recommended for children, which should be effective for pneumococci with high-level penicillin resistance and will also cover most infections with Haemophilus influenzae. Amoxicillin-clavulanate (in high-dose amoxicillin formulations available for both children and adults) should be considered the initial treatment of choice in patients with recent antibiotic therapy with amoxicillin (previous 30 days) and with resistant H. influenzae infections pending the results of studies of local epidemiology (β-lactamase production ≥15%). The macrolide/azalide class of antibiotics is not recommended routinely for URTIs and is reserved for β-lactam-allergic patients.Conclusion. These recommendations should facilitate rational antibiotic prescribing for URTIs as a component of antibiotic stewardship. They will require updating when new information becomes available, particularly from randomised controlled trials and surveillance studies of local aetiology and antibiotic susceptibility patterns.