A framework for the systematic realisation of phenomena for enhanced sensing of radiological and nuclear materials, and radiation.

The quest for new sensing phenomena continues because detecting, discriminating, identifying, measuring and monitoring nuclear materials and their radiation from greater range, at lower concentrations, and in a more timely fashion brings greater safety, security and efficiency. The potential phenomena are diverse, and those that have been realised can be found in disparate fields of science, engineering and medicine, which makes the full range difficult to realise and record. The framework presented here offers a means to systematically and comprehensively explore nuclear sensing phenomena. The approach is based on the fundamental concepts of matter and energy, where the sequence starts with the original nuclear material and its emissions, and progressively considers signatures arising from secondary effects and the emissions from associated materials and the environment. Concepts of operations such as active and passive interrogation, and networked sensing are considered. In this operational light, unpacking nuclear signatures forces a fresh look at the sensing concept. It also exposes how some phenomena that exist in established technology may be considered novel based on how they could be exploited rather than what they fundamentally are. This article selects phenomena purely to illustrate the framework and how it can be best used to foster creativity in the quest for novel phenomena rather than exhaustively listing, categorising or comparing any practical aspects of candidate phenomena.

Skin-prick testing as a diagnostic aid for childhood asthma.

Diagnosing asthma is problematic when based solely on reported symptoms. The purpose of this study was to evaluate skin-prick testing as a diagnostic aid for asthma in children. Skin-prick testing (SPT) was undertaken in children aged 2-10 years with either no history of wheeze (n = 149) or recent doctor-observed wheeze which responded to treatment with a bronchodilator, the "gold standard" (n = 164). Children with moderate or severe asthma were excluded. SPT positivity increased sharply at age 5 years in wheezers. Data were therefore divided into two age groups: 2- < 5 years (57 controls, 97 wheezers) and 5-10 years (92 controls, 67 wheezers). The sensitivity, specificity, and likelihood ratios of SPT positivity for wheeze were 32%, 89%, and 2.9, respectively, in the younger children, and 82%, 85%, and 5.5, respectively, in the older children. For a prevalence of 30% for asthma, the positive predictive values of a positive SPT were 55% and 70% for the younger and older age groups, respectively. The test characteristics of SPT for helping diagnose asthma in schoolchildren are good. The prevalence of wheeze in preschool children is high, and so SPT should be helpful even in this group. We suggest that clinicians consider skin-prick testing as a diagnostic aid for asthma.

Airway resistance by the interrupter technique: which algorithm for measuring pressure?

Airway resistance using the interrupter technique (Rint) can be measured using commercial devices which employ different algorithms for estimating pressure change. We aim to describe differences in Rint due to algorithm. We compared Rint and change in Rint after bronchodilator, using four algorithms to estimate pressure change following interruption: 1) two-point back-extrapolation to interruption from points 70 msec and 30 msec from interruption, and similarly 2) to 15 msec from interruption, 3) at two-thirds from interruption, and 4) near end-interruption. Flow was measured immediately before interruption. Our subjects were 39 asymptomatic children 2-5 years old with previous intermittent wheeze. Rint differed significantly with algorithm. Geometric mean Rint (95% confidence interval (CI)) for algorithms 1-4 were 1.21 kPa x l(-1) x sec (1.18-1.24 kPa x l(-1) x sec), 1.31 kPa x l(-1) x sec (1.28-1.34 kPa x l(-1) x sec), 1.57 kPa x l(-1) x sec (1.54-1.61 kPa x l(-1) x sec) and 1.71 kPa x l(-1) x sec (1.67-1.75 kPa x l(-1) x sec), respectively. Measurement of change in R(int) following bronchodilator (BDR) did not differ on average with algorithm. Geometric means (95% CI) for BDR measurements for algorithms 1-4 were 29.9% (26.0-34.0%), 30.4% (26.4-34.5%), 32.9% (28.8-37.1%), and 31.7% (27.6-35.8%), respectively. However, measurement of change in individuals could differ by up to 40%, depending on algorithm. In conclusion, there are significant differences in Rint, depending on algorithm used to estimate pressure change. Measurement of change in Rint is unaffected on average, although in individuals there could be significant differences. Each laboratory should state its method and use the same algorithm for longitudinal and group data.

Repeatability of airway resistance measurements made using the interrupter technique.

BACKGROUND: To be able to interpret any measurement, its repeatability should be known. This study reports the repeatability of airway resistance measurements using the interrupter technique (Rint) in children with and without respiratory symptoms. METHODS: Children aged 2-10 years who were healthy, had persistent isolated cough, or who had previous wheeze were studied. On the same occasion, three Rint measurements were made 15 minutes apart, before and after placebo and salbutamol given in random order. Results from those given placebo first were analysed for within-occasion repeatability. Between-occasion repeatability measurements were made 2-20 weeks apart (median 3 weeks). RESULTS: For 85 pairs of measurements before and after placebo the limits of agreement were 20% expected resistance and were unaffected by age or health status. The change in resistance following bronchodilator in one of 18 healthy children, 12 of 28 with cough, and 22 of 39 with wheeze exceeded this threshold. For between-occasion measurements the limits of agreement were 32% in 72 healthy subjects, 49% in 57 with cough, and 53% in 95 with previous wheeze. CONCLUSION: The measurement of airways resistance by the interrupter technique is clinically meaningful when change following an intervention such as the administration of bronchodilator is greater than its within-occasion repeatability. Between-occasion repeatability is too poor to judge change confidently.

Airway resistance measured by the interrupter technique: normative data for 2-10 year olds of three ethnicities.

BACKGROUND AND AIMS: The measurement of airway resistance using the interrupter technique (R(int)) is feasible in preschool children and other subjects unable to undertake spirometry. This makes it potentially useful for the measurement of lung function in these groups. Commercial devices use different algorithms to measure pressure and flow from which R(int) is derived. This study provides normative values for British children using devices from a single manufacturer. METHODS: R(int) was measured in 236 healthy children of three ethnic groups (Afro-Caribbean and black African, Bangladeshi, and white British) aged 2-10 years using Micro Medical devices. Software in the devices calculated R(int) from pressure measured by the two point, back extrapolation method from the pressure transient during valve closure, with flow measured just before valve closure. RESULTS: R(int) is related to both age and height, but when age is allowed for there is not a significant relation with height. Neither gender nor any of the ethnicities studied was significantly related to R(int). DISCUSSION: These measurements in healthy children using this technique may be used as reference data for similar populations.

Growth reference charts for use in the United Kingdom.

Since the introduction of new growth charts in the mid 1990s, there has been confusion about which charts should be used, with many districts using more than one version. Because of this uncertainty, an expert working party, the Growth Reference Review Group, was convened by the Royal College of Paediatrics and Child Health to provide guidance on the validity and comparability of the different charts currently in use. This paper describes the technical background to the construction and evaluation of growth charts and outlines the group's findings on the validity of each growth reference in relation to contemporary British children. The group concluded that for most clinical purposes the UK90 reference is superior and for many measures is the only usable reference that can be recommended, while the original Tanner-Whitehouse and the Gairdner-Pearson charts are no longer reliable for use at any age. After the age of 2 the revised Buckler-Tanner references are still suitable for assessing height. There are presently no reliable head circumference reference charts for use beyond infancy. The group propose that apart from refinements of chart design and layout, the new UK90 reference should now be "frozen", with any future revisions only undertaken after careful planning and widespread consultation.

Airway resistance and atopy in preschool children with wheeze and cough.

The extent to which the measurement of airways resistance by the interrupter technique (Rint) distinguishes preschool children with previous wheeze from those with no respiratory symptoms and helps to classify subjects with persistent cough, was investigated. Rint was measured before and after salbutamol treatment in 82 children with recurrent wheeze, 58 with isolated cough and 48 with no symptoms (control subjects). Their mean age (range) was 3.7 yrs (2-<5 yrs). Median baseline Rint was higher (p<0.0001) in wheezers than in either coughers or control subjects (1.16, 0.94 and 0.88 kPa x L(-1) x s(-1) respectively); coughers did not differ significantly from control subjects (p=0.14). The median ratios of baseline to post-salbutamol measurements (bronchodilator response (BDR)) in the groups differed significantly (1.40, 1.27 and 1.07, p< or =0.01 for all), suggesting that coughers occupy an intermediate position. A BDR ratio of >1.22 had a specificity and sensitivity for wheeze of 80% and 76% respectively. Twenty-eight coughers had a BDR ratio >1.22. Wheezers' immunoglobulin E was inversely related to baseline Rint. It is concluded that measurements of airway resistance by the interrupter technique are useful for classifying preschool children with respiratory symptoms and could be used to monitor the effect of interventions. The relation between atopy and airways resistance suggests that they have separate roles in preschool wheezing. Coughers with a high bronchodilator response could represent "cough-variant" asthma in children who have baseline airway resistance by the interrupter technique measurements similar to control subjects. Whether these children develop classical asthma will only be known at follow-up later in childhood.

Paradigms and pragmatism: approaches to medical statistics.

Until recently, the dominant philosophy of science was that due to Karl Popper, with its doctrine that the proper task of science was the formulation of hypotheses followed by attempts at refuting them. In spite of the close analogy with significance testing, these ideas do not fit well with the practice of medical statistics. The same can be said of the later philosophy of Thomas Kuhn, who maintains that science proceeds by way of revolutionary upheavals separated by periods of relatively pedestrian research which are governed by what Kuhn refers to as paradigms. Through there have been paradigm shifts in the history of statistics, a degree of continuity can also be discerned. A current paradigm shift is embodied in the spread of Bayesian ideas. It may be that a future paradigm will emphasise the pragmatic approach to statistics that is associated with the name of Daniel Schwartz.

Purification and kinetic characterisation of juvenile hormone esterase from Drosophila melanogaster.

Juvenile hormone esterase (JHE) from the prepupal stage of Drosophila melanogaster was purified about 429-fold to near homogeneity by selective precipitations, isoelectric focussing, anion exchange and gel filtration chromatography. The KM and Vmax of the purified enzyme for juvenile hormone III (JHIII) hydrolysis are 89 nM and at least 590 nmol/min/mg, respectively. JHE also hydrolyses the artificial substrate alpha-naphthyl acetate with a KM of 120 micro M and a Vmax of at least 70 mumol/min/mg. Competition of JHIII hydrolysis by five juvenile hormones and twenty-four JH analogues showed JHE is highly selective for JHIII and JHIII bisepoxide (JHP3), and both may be in vivo substrates. Binding in the active site of JHE is promoted by structural features found in JHIII and JHB3 including the epoxide groups in their natural orientations, methyl (rather than ethyl) side-chains, and the 2E, 3 double bond that is conjugated with the ester group. Binding is reduced by almost any departure from these structural features of JH. Co-incubation of the haemolymph JH binding protein, lipophorin, with JHE indicates lipophorin might modulate JH hydrolysis by competition for binding of JH.

Guaranteed two-pass convergence for supervised and inferential learning.

We present a theoretical analysis of a version of the LAPART adaptive inferencing neural network. Our main result is a proof that the new architecture, called LAPART 2, converges in two passes through a fixed training set of inputs. We also prove that it does not suffer from template proliferation. For comparison, Georgiopoulos et al. have proved the upper bound n-1 on the number of passes required for convergence for the ARTMAP architecture, where n is the size of the binary pattern input space. If the ARTMAP result is regarded as an n-pass, or finite-pass, convergence result, ours is then a two-pass, or fixed-pass, convergence result. Our results have added significance in that they apply to set-valued mappings, as opposed to the usual supervised learning model of affixing labels to classes.

Characterization of the EstP protein in Drosophila melanogaster and its conservation in drosophilids.

The beta-esterase cluster of D. melanogaster comprises two tandemly duplicated genes. Est6 encodes the well-characterized 5' gene, but the product of the second gene, denoted EstP, had not previously been identified. Here we show that the EstP gene encodes the carboxylesterase EST7. Expression of EstP using the Baculovirus system led to production of a carboxylesterase biochemically indistinguishable from EST7. Furthermore, a naturally occurring EstP variant produces greatly reduced amounts of EstP mRNA and no detectable EST7 protein. Finally, introduction of a wild-type copy of EstP by germline transformation into the variant strain confers the wild-type EST7 phenotype. We show that EST7 differs from EST6 in its substrate and inhibitor specificities and tissue distribution. Germline transformation experiments show that EstP expression is controlled by sequences located between 192 bp 5' and 609 bp 3' of the EstP coding region. Data comparisons with other drosophilid esterases suggest that the site of expression and hence the function, of EST7 has been conserved across lineages in both the subgenera Drosophila and Sophophora.

Acquiring rule sets as a product of learning in a logical neural architecture.

Envisioning neural networks as systems that learn rules calls forth the verification issues already being studied in knowledge-based systems engineering, and complicates these with neural-network concepts such as nonlinear dynamics and distributed memories. We show that the issues can be clarified and the learned rules visualized symbolically by formalizing the semantics of rule-learning in the mathematical language of two-valued predicate logic. We further show that this can, at least in some cases, be done with a fairly simple logical model. We illustrate this with a combination of two example neural-network architectures, LAPART, designed to learn rules as logical inferences from binary data patterns, and the stack interval network, which converts real-valued data into binary patterns that preserve the semantics of the ordering of real values. We discuss the significance of the formal model in facilitating the analysis of the underlying logic of rule-learning and numerical data representation. We provide examples to illustrate the formal model, with the combined stack interval/LAPART networks extracting rules from numerical data.

Growth of the uterus.

BACKGROUND: The pattern of growth of the uterus was examined by ultrasound examinations of 358 girls who attended a paediatric endocrine outpatient department but were shown not to have any endocrine defect. METHOD: The uterus was measured in length and width at the cervix and at the fundus (cm). Endometrial thickness was measured (mm). Scans were divided by Tanner breast stage and the dimensions compared by one way analysis of variance (ANOVA, with the Student Newman Keuls post hoc test). RESULTS: There was an increase in uterine length, diameter of the fundus, and endometrial thickness at each breast stage from 1 to 5 (ANOVA, p < 0.05), and in the diameter of the cervix with each breast stage from 1 to 4 (ANOVA, p < 0.05). The ratio of the fundus to the cervix increased from 0.95 to 1.29 between breast stages 1 and 4. CONCLUSION: The onset of puberty is marked by an increase in the dimensions of the uterus and in endometrial thickness, but also by a change in the shape of the uterus from a tubular to a pear shaped organ.

Localization of sequences regulating ancestral and acquired sites of esterase6 activity in Drosophila melanogaster.

We have broadly defined the DNA regions regulating esterase6 activity in several life stages and tissue types of D. melanogaster using P-element-mediated transformation of constructs that contain the esterase6 coding region and deletions or substitutions in 5' or 3' flanking DNA. Hemolymph is a conserved ancestral site of EST6 activity in Drosophila and the primary sequences regulating its activity lie between -171 and -25 bp relative to the translation initiation site: deletion of these sequences decrease activity approximately 20-fold. Hemolymph activity is also modulated by four other DNA regions, three of which lie 5' and one of which lies 3' of the coding region. Of these, two have positive and two have negative effects, each of approximately twofold. Esterase6 activity is present also in two male reproductive tract tissues; the ejaculatory bulb, which is another ancestral activity site, and the ejaculatory duct, which is a recently acquired site within the melanogaster species subgroup. Activities in these tissues are at least in part independently regulated: activity in the ejaculatory bulb is conferred by sequences between -273 and -172 bp (threefold decrease when deleted), while activity in the ejaculatory duct is conferred by more distal sequences between -844 and -614 bp (fourfold decrease when deleted). The reproductive tract activity is further modulated by two additional DNA regions, one in 5' DNA (-613 to -284 bp; threefold decrease when deleted) and the other in 3' DNA (+1860 to +2731 bp; threefold decrease when deleted) that probably overlaps the adjacent esteraseP gene. Collating these data with previous studies suggests that expression of EST6 in the ancestral sites is mainly regulated by conserved proximal sequences while more variable distal sequences regulate expression in the acquired ejaculatory duct site.