On realizing diagrams of Pi-algebras

Given a diagram of Pi-algebras (graded groups equipped with an action of the primary homotopy operations), we ask whether it can be realized as the homotopy groups of a diagram of spaces. The answer given here is in the form of an obstruction theory, of somewhat wider application, formulated in terms of generalized Pi-algebras. This extends a program begun in [J. Pure Appl. Alg. 103 (1995) 167-188] and [Topology 43 (2004) 857-892] to study the realization of a single Pi-algebra. In particular, we explicitly analyze the simple case of a single map, and provide a detailed example, illustrating the connections to higher homotopy operations.Comment: This is the version published by Algebraic & Geometric Topology on 21 June 200

Block of endplate channels by permeant cations in frog skeletal muscle

Motor endplates of frog semitendinosus muscles were studied under voltage clamp. Current fluctuations by iontophoretic application of acetylcholine were analyzed to give the elementary conductance, γ, and mean open time, τ, of endplate channels. Total replacement of the external Na+ ion by several other metal ions and by many permanent organic cations changed both γ and τ. Except with NH4 + ions, the γ values with foreign test ions were all smaller than expected from the independence relation and their previously measured permeability ratios. The more hydrophobic ions gave the smallest γ values. Foreign permeant cations also depress γ when mixed with Na+ ions. These effects could be interpreted in terms of binding of ions to a saturable site within the endplate channel as they pass through. The site for organic ions would have a hydrophobic component. Similar evidence is given for a metal ion binding site on the cytoplasmic end of the channel accessible to internal ions. Most foreign cations also shortened τ when applied externally. The changes of gating did not seem to be correlated with changes in γ. Thus there is no evidence for control of τ by ions bound within the pore

The Quantity Theory of Money is Valid. The New Keynesians are Wrong!

We test the quantity theory of money (QTM) using a novel approach and a large new sample. We do not follow the usual approach of first differentiating the logarithm of the Cambridge equation to obtain an equation relating the growth rate of real GDP, the growth rate of money and inflation. These variables must then again be ‘integrated’ by averaging in order to obtain stable relationships. Instead we suggest a much simpler procedure for testing directly the stability of the coefficient of the Cambridge equation. For 125 countries and post-war data we find the coefficient to be surprisingly stable. We do not select for high inflation episodes as was done in most empirical studies; inflation rates do not even appear in our data set. Much work supporting the QTM has been done by economic historians and at the University of Chicago by Milton Friedman and his associates. The QTM was a foundation stone of the monetarist revolution. Subsequently belief in it waned. The currently dominant New Keynesian School, implicitly or explicitly denies the validity of the QTM. We survey this history and argue that the QTM is valid and New Keynesians are wrong

Positron clouds within thunderstorms

We report the observation of two isolated clouds of positrons inside an active thunderstorm. These observations were made by the Airborne Detector for Energetic Lightning Emissions (ADELE), an array of six gamma-ray detectors, which flew on a Gulfstream V jet aircraft through the top of an active thunderstorm in August 2009. ADELE recorded two 511 keV gamma-ray count rate enhancements, 35 seconds apart, each lasting approximately 0.2 seconds. The enhancements, which were about a factor of 12 above background, were both accompanied by electrical activity as measured by a flat-plate antenna on the underside of the aircraft. The energy spectra were consistent with a source mostly composed of positron annihilation gamma rays, with a prominent 511 keV line clearly visible in the data. Model fits to the data suggest that the aircraft was briefly immersed in clouds of positrons, more than a kilometer across. It is not clear how the positron clouds were created within the thunderstorm, but it is possible they were caused by the presence of the aircraft in the electrified environment.Comment: Accepted for publication in the Journal of Plasma Physic

Influenza Vaccine Effectiveness against Hospitalisation with Confirmed Influenza in the 2010-11 Seasons: A Test-negative Observational Study

Immunisation programs are designed to reduce serious morbidity and mortality from influenza, but most evidence supporting the effectiveness of this intervention has focused on disease in the community or in primary care settings. We aimed to examine the effectiveness of influenza vaccination against hospitalisation with confirmed influenza. We compared influenza vaccination status in patients hospitalised with PCR-confirmed influenza with patients hospitalised with influenza-negative respiratory infections in an Australian sentinel surveillance system. Vaccine effectiveness was estimated from the odds ratio of vaccination in cases and controls. We performed both simple multivariate regression and a stratified analysis based on propensity score of vaccination. Vaccination status was ascertained in 333 of 598 patients with confirmed influenza and 785 of 1384 test-negative patients. Overall estimated crude vaccine effectiveness was 57% (41%, 68%). After adjusting for age, chronic comorbidities and pregnancy status, the estimated vaccine effectiveness was 37% (95% CI: 12%, 55%). In an analysis accounting for a propensity score for vaccination, the estimated vaccine effectiveness was 48.3% (95% CI: 30.0, 61.8%). Influenza vaccination was moderately protective against hospitalisation with influenza in the 2010 and 2011 seasons

“It’s my dream to work with Olympic athletes”: Neophyte sport psychologists’ expectations and initial experiences regarding service delivery

We examined trainee practitioners' initial experiences of applied sport psychology practice. Semi-structured interviews (4) were conducted over 6 months with 7 full-time MSc students before, during, and after the applied sport psychology module, when they were working with clients. Participants also kept reflective diaries over an 8-week period whilst working with clients. Findings included: (a) motivations and expectations of an ASP practice career, (b) perceptions of service delivery, (c) emotional demands, and (d) pivotal experiences. Findings extend previous literature on the initial stages of practitioner development, providing micro-level detail on aspects of the intense development process during this pivotal perio

Flexible trial design in practice – dropping and adding arms in STAMPEDE: a multi-arm multi-stage randomised controlled trial

The trial recruits men with locally advanced or metastatic prostate cancer starting standard long-term hormone therapy. There are 5 research arms and 1 control arm. The trial has a pilot stage assessing safety and feasibility, 3 intermediate “activity” stages (I-III) where the outcome measure is failure-free survival (FFS) and one final “efficacy” stage (IV) with overall survival as primary outcome measure. At the end of each stage, each research arm is formally compared pairwise to the control arm. Accrual of further patients is discontinued early for any research arm either not showing sufficient evidence of activity or with adverse safety considerations; accrual continues to arms showing activity with acceptable safety. The stopping guideline compares the treatment effect against a pre-defined cut-off value using the hazard ratio when the hazards are proportional and restricted-mean survival time otherwise. This interim hurdle becomes increasingly stringent stage-by-stage. The addition of new research arm(s) can be actively considered when sufficiently interesting agents emerge. New research arms are compared only to contemporaneously-recruited control arm patients using the same intermediate guidelines in a time-delayed manner. The addition of new research arms is independent of any of the original research arms stopping accrual early subject to adequate recruitment to support the overall trial aims

Sudden Heart Rate Reduction Upon Optogenetic Release of Acetylcholine From Cardiac Parasympathetic Neurons in Perfused Hearts

The balance of sympathetic and parasympathetic tone provides exquisite control of heart rate and contractility and has also been shown to modulate coronary flow and inflammation. Understanding how autonomic balance is altered by cardiac disease is an active area of research, and developing new ways to control this balance provides insights into disease therapies. However, achieving acute neuron-specific stimulation of autonomic neurons can be difficult in experiments that measure the acute effects of nerve stimulation on the heart. Conventional electrical and pharmacological approaches can be spatially and temporally non-selective. Cell-specific expression of light-activated channels (channelrhodopsin, ChR2) is a powerful approach that enables control of the timing and distribution of cellular stimulation using light. We present such an optogenetic approach where parasympathetic cardiac neurons are selectively photoactivated at high temporal precision to initiate cholinergic-mediated slowing of heart rate. Mice were crossbred to express ChR2 in peripheral cholinergic neurons using Cre-Lox recombination driven by a choline acetyltransferase (ChAT) promoter. Hearts from adult mice were excised, perfused, and the epicardium was illuminated (peak 460–465 nm) to photoactivate ChR2. In one set of studies, hearts were illuminated using a large-field LED light source. In other studies, a micro LED was placed on the right atrium to selectively illuminate the junction of the superior vena cava (SVC) and right atrium. The ECG was acquired before, during, and after tissue illumination to measure changes in heart rate. Upon illumination, hearts exhibited sudden and dramatic reductions in heart rate with restoration of normal heart rate after cessation of illumination. Delays in atrioventricular conduction were also observed. Heart rate reductions at the highest irradiance levels were similar to heart rate reductions caused by application of bethanechol (10 μM) or acetylcholine (800 μM). Atropine (50 nM) completely blocked the effect of ChR2 photoactivation, confirming cholinergic mediation. Optogenetic activation of intrinsic parasympathetic neurons reduced heart rate in an immediate, dose-dependent fashion, resembling the slowing of sinus rate in response to acetylcholine. Our results demonstrate a new approach for controlling parasympathetic modulation of cardiac function by selectively activating the endogenous release of acetylcholine from intrinsic cardiac cholinergic neurons.Key Message: Optogenetic photoactivation of intrinsic cardiac neurons provides immediate, tissue-specific stimulation with minimal cross-reactivity. Our results demonstrate that selective expression of channelrhodopsin within cardiac cholinergic neurons enables photoactivated release of acetylcholine, thereby instantaneously slowing sinus rate and altering atrioventricular conduction. This provides for in-depth examination of the endogenous interplay between cardiac autonomic neurons and the functional outcomes of downstream post-synaptic receptor activation

Simplicity in Visual Representation: A Semiotic Approach

Simplicity, as an ideal in the design of visual representations, has not received systematic attention. High-level guidelines are too general, and low-level guidelines too ad hoc, too numerous, and too often incompatible, to serve in a particular design situation. This paper reviews notions of visual simplicity in the literature within the analytical framework provided by Charles Morris' communication model, specifically, his trichotomy of communication levels—the syntactic, the semantic, and the pragmatic. Simplicity is ultimate ly shown to entail the adjudication of incompatibilities both within, and between, levels.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68281/2/10.1177_105065198700100103.pd