Diagnosis of asthma in symptomatic children based on measures of lung function: an analysis of data from a population-based birth cohort study.

BACKGROUND: Concerns have been expressed about asthma overdiagnosis. The UK National Institute of Health and Care Excellence (NICE) proposed a new diagnostic algorithm applying four lung function measures sequentially (ratio of forced expiratory volume in 1 s [FEV1] to forced vital capacity [FVC] 20%). We aimed to assess the diagnostic value of three of the tests individually, and then test the proposed algorithm in symptomatic children. METHODS: We used follow-up data at age 13-16 years from the Manchester Asthma and Allergy Study, a prospective, population-based, birth cohort study. We initially present results for the whole population, then by subgroup of disease. To simulate the situation in primary care, we included participants reporting symptoms of wheeze, cough, or breathlessness in the previous 12 months and who were not on regular inhaled corticosteroids. We used an epidemiological definition of current asthma, defined as all three of physician-diagnosed asthma, current wheeze, and current use of asthma treatment, reported by parents in a validated questionnaire. We assigned children with negative answers to all three questions as non-asthmatic controls. We also measured spirometry, bronchodilator reversibility, and FeNO at follow-up; data for peak expiratory flow variability were not available. We calculated the proportion of participants with a current positive lung function test at each step of the algorithm, and recorded the number of participants that met our definition of asthma. FINDINGS: Of 1184 children born into the cohort, 772 attended follow-up at age 13-16 years between July 22, 2011, and Nov 11, 2014. Among 630 children who completed spirometry, FEV1:FVC was less than 70% in ten (2%) children, of whom only two (20%) had current asthma. Bronchodilator reversibility was positive in 54 (9%) of 624 children, of whom only 12 (22%) had current asthma. FeNO was 35 or more parts per billion in 115 (24%) of 485 children, of whom 29 (25%) had current asthma. Only four of 56 children with current asthma had positive results for all three tests (spirometry, bronchodilator reversibility, and FeNO). Conversely, 24 (43%) of the 56 children with current asthma were negative on all three tests. FEV1:fvc (p=0·0075) and FeNO (p<0·0001), but not bronchodilator reversibility (p=0·97), were independently associated with asthma in multivariable logistic regression models. Among children who reported recent symptoms, the diagnostic accuracy of the algorithm was poor. INTERPRETATION: Our findings challenge the proposed cutoff values for spirometry, the order in which the lung function tests are done, and the position of bronchodilator reversibility within the algorithm sequence. Until better evidence is available, the proposed NICE algorithm on asthma diagnosis should not be implemented in children. FUNDING: UK Medical Research Council

Fano resonances in a three-terminal nanodevice

The electron transport through a quantum sphere with three one-dimensional wires attached to it is investigated. An explicit form for the transmission coefficient as a function of the electron energy is found from the first principles. The asymmetric Fano resonances are detected in transmission of the system. The collapse of the resonances is shown to appear under certain conditions. A two-terminal nanodevice with an additional gate lead is studied using the developed approach. Additional resonances and minima of transmission are indicated in the device.Comment: 11 pages, 5 figures, 2 equations are added, misprints in 5 equations are removed, published in Journal of Physics: Condensed Matte

Prebiotic synthesis of cysteine peptides that catalyze peptide ligation in neutral water

Peptide biosynthesis is performed by ribosomes and several other classes of enzymes, but a simple chemical synthesis may have created the first peptides at the origins of life. a-Aminonitriles—prebiotic a–amino acid precursors—are generally produced by Strecker reactions. However, cysteine’s aminothiol is incompatible with nitriles. Consequently, cysteine nitrile is not stable, and cysteine has been proposed to be a product of evolution, not prebiotic chemistry. We now report a high-yielding, prebiotic synthesis of cysteine peptides. Our biomimetic pathway converts serine to cysteine by nitrile-activated dehydroalanine synthesis. We also demonstrate that N-acylcysteines catalyze peptide ligation, directly coupling kinetically stable—but energy-rich—a-amidonitriles to proteinogenic amines. This rare example of selective and efficient organocatalysis in water implicates cysteine as both catalyst and precursor in prebiotic peptide synthesis

Snake orbits and related magnetic edge states

We study the electron motion near magnetic field steps at which the strength and/or sign of the magnetic field changes. The energy spectrum for such systems is found and the electron states (bound and scattered) are compared with their corresponding classical paths. Several classical properties as the velocity parallel to the edge, the oscillation frequency perpendicular to the edge and the extent of the states are compared with their quantum mechanical counterpart. A class of magnetic edge states is found which do not have a classical counterpart.Comment: 8 pages, 10 figure

Two-dimensional electron gas in a linearly varying magnetic field: Quantization of the electron and current density

Published versio

Suitability versus fidelity for rating single-photon guns

The creation of specified quantum states is important for most, if not all, applications in quantum computation and communication. The quality of the state preparation is therefore an essential ingredient in any assessment of a quantum-state gun. We show that the fidelity, under the standard definitions is not sufficient to assess quantum sources, and we propose a new measure of suitability that necessarily depends on the application for the source. We consider the performance of single-photon guns in the context of quantum key distribution (QKD) and linear optical quantum computation. Single-photon sources for QKD need radically different properties than sources for quantum computing. Furthermore, the suitability for single-photon guns is discussed explicitly in terms of experimentally accessible criteria.Comment: 4 pages, 2 figures Revised per referee suggestion

Interferometric Tests of Teleportation

We investigate a direct test of teleportation efficacy based on a Mach-Zehnder interferometer. The analysis is performed for continuous variable teleportation of both discrete and continuous observables

Quantum M\"{u}nchhausen effect in tunneling

It is demonstrated that radiative corrections increase tunneling probability of a charged particle

Measuring Terrestrial Area of Habitat (AOH) and Its Utility for the IUCN Red List

The International Union for Conservation of Nature (IUCN) Red List of Threatened Species includes assessment of extinction risk for 98 512 species, plus documentation of their range, habitat, elevation, and other factors. These range, habitat and elevation data can be matched with terrestrial land cover and elevation datasets to map the species’ area of habitat (AOH; also known as extent of suitable habitat; ESH). This differs from the two spatial metrics used for assessing extinction risk in the IUCN Red List criteria: extent of occurrence (EOO) and area of occupancy (AOO). AOH can guide conservation, for example, through targeting areas for field surveys, assessing proportions of species’ habitat within protected areas, and monitoring habitat loss and fragmentation. We recommend that IUCN Red List assessments document AOH wherever practical

Washing hands and risk of cross-contamination during chicken preparation among domestic practitioners in five European countries

Nearly 40% foodborne outbreaks in the European Union are attributable to food practices in domestic homes that include handling and preparation of raw chicken. Hand washing is an important way to prevent cross-contamination with pathogens during chicken preparation. This study, which is part of the EU Horizon 2020 funded consortium SafeConsume, aimed at quantifying and understanding hand washing practices in three categories of households and five European countries. A quantitative survey (n = 1889) was combined with qualitative research, during which 75 participants from France, Norway, Portugal, Romania, and the United Kingdom were observed and interviewed. An original method for analysing video with “The Observer XT” software was developed to identify when and how risk arises. The quantitative survey and qualitative research data revealed that touching raw chicken was more frequent in Romania and Portugal. Practices to avoid touching raw chicken were declared and observed, although observations revealed that these practices were not always consistently followed. Only a third of the participants washed their hands with soap after handling raw chicken with important variations among countries (a majority in Norway and in the UK, a few in France and Portugal, none in Romania), in contrast to the results of the survey. Observations and interviews suggested that rinsing hands with water only and washing hands with soap are considered equivalent by many people. Barriers to washing hands due to improper equipment were mainly observed in Romania. Washing hands after touching raw chicken was motivated by food safety concerns for some participants in Norway and the UK, but not in France and Portugal, where it was motivated by unpleasant feelings on hands, or presented as a habit. Participants not washing their hands after touching the chicken did it after other actions they presumably perceived as unsafe (e.g. touching the bin, handling pets, and blowing the nose), indicating that they did not specifically consider touching raw chicken as risky. Knowledge, habits, and equipment with regard to chicken and hand washing differed among European countries, resulting in safe and risky practices