A Refined Neuronal Population Measure of Visual Attention

Neurophysiological studies of cognitive mechanisms such as visual attention typically ignore trial-by-trial variability and instead report mean differences averaged across many trials. Advances in electrophysiology allow for the simultaneous recording of small populations of neurons, which may obviate the need for averaging activity over trials. We recently introduced a method called the attention axis that uses multi-electrode recordings to provide estimates of attentional state of behaving monkeys on individual trials. Here, we refine this method to eliminate problems that can cause bias in estimates of attentional state in certain scenarios. We demonstrate the sources of these problems using simulations and propose an amendment to the previous formulation that provides superior performance in trial-by-trial assessments of attentional state

Are beta-2-agonists or anticholinergics more effective for treating COPD?

Both β2-agonists and anticholinergics appear to improve symptoms for patients with chronic obstructive pulmonary disease (COPD). Recent research indicates that adding a long-acting anti-cholinergic to a β2-agonist may improve quality of life for patients with stable COPD more than the use of β2-agonists alone. Both drug classes increase exercise capacity and alleviate symptoms of COPD, although neither alters disease progression (strength of recommendation [SOR]: A). Combination therapy can lead to greater improvements in forced expiratory volume in 1 second (FEV1) than either drug alone (SOR: A). However, until recently there were no convincing direct head-to-head comparisons of the 2 classes, and it is unclear whether this difference is clinically significant

Nerve Agent Hydrolysis Activity Designed into a Human Drug Metabolism Enzyme

Organophosphorus (OP) nerve agents are potent suicide inhibitors of the essential neurotransmitter-regulating enzyme acetylcholinesterase. Due to their acute toxicity, there is significant interest in developing effective countermeasures to OP poisoning. Here we impart nerve agent hydrolysis activity into the human drug metabolism enzyme carboxylesterase 1. Using crystal structures of the target enzyme in complex with nerve agent as a guide, a pair of histidine and glutamic acid residues were designed proximal to the enzyme's native catalytic triad. The resultant variant protein demonstrated significantly increased rates of reactivation following exposure to sarin, soman, and cyclosarin. Importantly, the addition of these residues did not alter the high affinity binding of nerve agents to this protein. Thus, using two amino acid substitutions, a novel enzyme was created that efficiently converted a group of hemisubstrates, compounds that can start but not complete a reaction cycle, into bona fide substrates. Such approaches may lead to novel countermeasures for nerve agent poisoning

Exile Vol. XVI No. 1

DRAMA God\u27s Pocket by Robert R. Bowie, Jr. 5-12 FICTION The Wagon by John Anderson 18-19 An Infinity of Mirrors by Keith McWalter 23-25 Commitment by John Whitt 28-29 It began not long ago... by Linda Notzelman 32-33 Jaundiced Evening by John Benes 35-39 POETRY Paralysis Outline by Lauren Shakely 13 A Woman Reads Camus by Lauren Shakely 14 don\u27t sell my rings by Lauren Shakely 14 Drift by John Whitt 17 Haiku by M. S. Wallace 19 To Begin W. K. Mayo 19 Dark is Right by Louise Tate 20 I am waiting by Louise Tate 21 My mother died as I shall die by Tim Cope 20 I never blamed you by Tim Cope 26 For Miss Didawick by Tim Cope 34 Separidian by Bill Whitmore 27 He walks on into by Whitney Carman 31 As Drowned Men Rise by Paul Bennett 34 The Tolling of the Bell by Keith McWalter 39 ARTWORK by Wandi Solez 4, 13, 16, 22, 36 by W. A. Hoffman 21, 30 by Stephen Sneeringer 27 by Christine Michael 19 Cover & Title Page Design: Keith McWalter Layouts: Keith McWalter Publicity- Special thanks to Gail Moore and Karen Baker Photographs courtesy the Sierra Club- From NOT MAN APART, Copyright 196

Evolution Equation of Phenotype Distribution: General Formulation and Application to Error Catastrophe

An equation describing the evolution of phenotypic distribution is derived using methods developed in statistical physics. The equation is solved by using the singular perturbation method, and assuming that the number of bases in the genetic sequence is large. Applying the equation to the mutation-selection model by Eigen provides the critical mutation rate for the error catastrophe. Phenotypic fluctuation of clones (individuals sharing the same gene) is introduced into this evolution equation. With this formalism, it is found that the critical mutation rate is sometimes increased by the phenotypic fluctuations, i.e., noise can enhance robustness of a fitted state to mutation. Our formalism is systematic and general, while approximations to derive more tractable evolution equations are also discussed.Comment: 22 pages, 2 figure

Cosmic Ray Background Analysis for a Cargo Container Counter.

We have developed a new model for calculating the expected yield of cosmic-ray spallation neutrons in a Cargo Container Counter, and we have benchmarked the model against measurements made with several existing large neutron counters. We also developed two versions of a new measurement uncertainty prediction code based on Microsoft Excel spreadsheets. The codes calculate the minimum detectability limit for the Cargo Container Counter for either neutron singles or doubles counting, and also propagate the uncertainties associated with efficiency normalization flux monitors and cosmic ray flux monitors. This paper will describe the physics basis for this analysis, and the results obtained for several different counter designs

Disruption, control and coping: responses of and to the person with dementia in hospital

This qualitative study aimed to gain insight into the experience of hospitalisation from the perspectives of the older person with dementia, their family care-giver and other patients sharing the ward (co-patients). Non-participant observation of care on 11 acute hospital wards was supplemented by 39 semi-structured interviews with 35 family care-givers and four co-patients following discharge. Constant comparative analysis produced the core problem facing all those involved: disruption from normal routine meaning that the experience of hospitalisation was disrupted by the presence and behaviour of the person with dementia. Disruption adversely affected the person with dementia, triggering constructive, disengaged, distressed and neutral behaviours. Using Kitwood's model of person-centred care, these behaviours were interpreted as attempts by the person with dementia at gaining a sense of control over the unfamiliar environment and experience. Family care-givers' lives and experiences both inside and outside the hospital were disrupted by the hospitalisation. They too attempted to gain a sense of control over the experience and to give a sense of control to the patient, co-patients and staff. Co-patients experienced disruption from sharing space with the person with dementia and were left feeling vulnerable and sometimes afraid. They too attempted to gain a sense of control over their situation and give some control by helping the person with dementia, the family care-giver and the staff

Thrombolytic removal of intraventricular haemorrhage in treatment of severe stroke: results of the randomised, multicentre, multiregion, placebo-controlled CLEAR III trial

Background: Intraventricular haemorrhage is a subtype of intracerebral haemorrhage, with 50% mortality and serious disability for survivors. We aimed to test whether attempting to remove intraventricular haemorrhage with alteplase versus saline irrigation improved functional outcome. Methods: In this randomised, double-blinded, placebo-controlled, multiregional trial (CLEAR III), participants with a routinely placed extraventricular drain, in the intensive care unit with stable, non-traumatic intracerebral haemorrhage volume less than 30 mL, intraventricular haemorrhage obstructing the 3rd or 4th ventricles, and no underlying pathology were adaptively randomly assigned (1:1), via a web-based system to receive up to 12 doses, 8 h apart of 1 mg of alteplase or 0·9% saline via the extraventricular drain. The treating physician, clinical research staff, and participants were masked to treatment assignment. CT scans were obtained every 24 h throughout dosing. The primary efficacy outcome was good functional outcome, defined as a modified Rankin Scale score (mRS) of 3 or less at 180 days per central adjudication by blinded evaluators. This study is registered with ClinicalTrials.gov, NCT00784134. Findings: Between Sept 18, 2009, and Jan 13, 2015, 500 patients were randomised: 249 to the alteplase group and 251 to the saline group. 180-day follow-up data were available for analysis from 246 of 249 participants in the alteplase group and 245 of 251 participants in the placebo group. The primary efficacy outcome was similar in each group (good outcome in alteplase group 48% vs saline 45%; risk ratio [RR] 1·06 [95% CI 0·88–1·28; p=0·554]). A difference of 3·5% (RR 1·08 [95% CI 0·90–1·29], p=0·420) was found after adjustment for intraventricular haemorrhage size and thalamic intracerebral haemorrhage. At 180 days, the treatment group had lower case fatality (46 [18%] vs saline 73 [29%], hazard ratio 0·60 [95% CI 0·41–0·86], p=0·006), but a greater proportion with mRS 5 (42 [17%] vs 21 [9%]; RR 1·99 [95% CI 1·22–3·26], p=0·007). Ventriculitis (17 [7%] alteplase vs 31 [12%] saline; RR 0·55 [95% CI 0·31–0·97], p=0·048) and serious adverse events (114 [46%] alteplase vs 151 [60%] saline; RR 0·76 [95% CI 0·64–0·90], p=0·002) were less frequent with alteplase treatment. Symptomatic bleeding (six [2%] in the alteplase group vs five [2%] in the saline group; RR 1·21 [95% CI 0·37–3·91], p=0·771) was similar. Interpretation: In patients with intraventricular haemorrhage and a routine extraventricular drain, irrigation with alteplase did not substantially improve functional outcomes at the mRS 3 cutoff compared with irrigation with saline. Protocol-based use of alteplase with extraventricular drain seems safe. Future investigation is needed to determine whether a greater frequency of complete intraventricular haemorrhage removal via alteplase produces gains in functional status