Predictive value of respiratory symptoms and bronchial hyperresponsiveness to diagnose asthma in New Zealand

SummaryRespiratory symptoms are often used as the only diagnostic criteria for asthma in epidemiological surveys and the clinical diagnosis of asthma relies primarily on a detailed history. The aim of this study is to predict the diagnostic value of 11 different respiratory symptoms to diagnose asthma, and to determine if bronchial hyperresponsiveness (BHR) improves the predictive value of these respiratory symptoms.A random sample of 1257 subjects aged 20–44 years old in 3 different areas of New Zealand were selected between March 1991 and December 1992 to answer the European Community Respiratory Health Survey questionnaire on respiratory symptoms. Of these, 784 underwent bronchial challenge with methacholine. The prevalence of current doctor diagnosed asthma (DDA) defined as asthma confirmed by a physician and an asthma attack in the last 12 months was 8.3%. Wheezing with dyspnoea is the single best predictor of diagnosed asthma with a sensitivity of 82%, a specificity of 90% and a Youden's index of 0.72. Wheezing alone is more sensitive (94%) but less specific (76%), with a Youden's index of 0.70. The addition of BHR to asthma symptoms decreases sensitivity and increases specificity with a small increase in Youden's index to 0.75. In New Zealand adults, a history of wheezing with BHR best predicts a diagnosis of asthma but wheezing alone or with dyspnoea are the two best symptoms for predicting asthma

Długotrwała ocena okskarbazepiny w warunkach naturalnych: badanie retrospektywne

Wprowadzenie. Pacjenci lepiej tolerują nowe leki przeciwpadaczkowe. Współczynnik retencji leków przeciwpadaczkowych może być użytecznym wskaźnikiem ich praktycznego zastosowania. Cel. Ocena długotrwałych wyników stosowania okskarbazepiny w warunkach naturalnych poprzez wyznaczenie współczynnika retencji. Metoda. Badanie retrospektywne, do którego włączono wszystkich chorych na padaczkę, leczonych okskarbazepiną w okresie 3,5 roku w referencyjnym ośrodku leczenia padaczki. Współczynnik retencji okskarbazepiny w 1. i 3. roku terapii był estymowany dla każdej grupy badawczej przy użyciu metody Kaplana-Meiera i mieścił się w 95-procentowym przedziale ufności. Wyniki. Przebadano grupę 98 osób. Okskarbazepinę stosowano w monoterapii u 14 pacjentów (14,3%), a jako lek dodatkowy - u 84 (85,7%). Średnia dawka dzienna wynosiła 947 ± 492 mg; 60% badanych otrzymywało 900 mg na dobę lub mniej. Stosując analizę przeżycia Kaplana-Meiera, wyznaczono retrospektywnie współczynnik retencji okskarbazepiny w 1. i 3. roku na poziomie odpowiednio 0,853 (0,749-0,956) i 0,737 (0,570-0,904). Wnioski. Okskarbazepina, zarówno stosowana w monoterapii, jak i w leczeniu skojarzonym, jest lekiem dobrze tolerowanym przez pacjentów

Sympathetic and hemodynamic responses to exercise in heart failure with preserved ejection fraction

Excessive sympathetic activity during exercise causes heightened peripheral vasoconstriction, which can reduce oxygen delivery to active muscles, resulting in exercise intolerance. Although both patients suffering from heart failure with preserved and reduced ejection fraction (HFpEF and HFrEF, respectively) exhibit reduced exercise capacity, accumulating evidence suggests that the underlying pathophysiology may be different between these two conditions. Unlike HFrEF, which is characterized by cardiac dysfunction with lower peak oxygen uptake, exercise intolerance in HFpEF appears to be predominantly attributed to peripheral limitations involving inadequate vasoconstriction rather than cardiac limitations. However, the relationship between systemic hemodynamics and the sympathetic neural response during exercise in HFpEF is less clear. This mini review summarizes the current knowledge on the sympathetic (i.e., muscle sympathetic nerve activity, plasma norepinephrine concentration) and hemodynamic (i.e., blood pressure, limb blood flow) responses to dynamic and static exercise in HFpEF compared to HFrEF, as well as non-HF controls. We also discuss the potential of a relationship between sympathetic over-activation and vasoconstriction leading to exercise intolerance in HFpEF. The limited body of literature indicates that higher peripheral vascular resistance, perhaps secondary to excessive sympathetically mediated vasoconstrictor discharge compared to non-HF and HFrEF, drives exercise in HFpEF. Excessive vasoconstriction also may primarily account for over elevations in blood pressure and concomitant limitations in skeletal muscle blood flow during dynamic exercise, resulting in exercise intolerance. Conversely, during static exercise, HFpEF exhibit relatively normal sympathetic neural reactivity compared to non-HF, suggesting that other mechanisms beyond sympathetic vasoconstriction dictate exercise intolerance in HFpEF

JWalk: a tool for lazy, systematic testing of java classes by design introspection and user interaction

Popular software testing tools, such as JUnit, allow frequent retesting of modified code; yet the manually created test scripts are often seriously incomplete. A unit-testing tool called JWalk has therefore been developed to address the need for systematic unit testing within the context of agile methods. The tool operates directly on the compiled code for Java classes and uses a new lazy method for inducing the changing design of a class on the fly. This is achieved partly through introspection, using Java’s reflection capability, and partly through interaction with the user, constructing and saving test oracles on the fly. Predictive rules reduce the number of oracle values that must be confirmed by the tester. Without human intervention, JWalk performs bounded exhaustive exploration of the class’s method protocols and may be directed to explore the space of algebraic constructions, or the intended design state-space of the tested class. With some human interaction, JWalk performs up to the equivalent of fully automated state-based testing, from a specification that was acquired incrementally

Algorithm for normal random numbers

We propose a simple algorithm for generating normally distributed pseudo random numbers. The algorithm simulates N molecules that exchange energy among themselves following a simple stochastic rule. We prove that the system is ergodic, and that a Maxwell like distribution that may be used as a source of normally distributed random deviates follows when N tends to infinity. The algorithm passes various performance tests, including Monte Carlo simulation of a finite 2D Ising model using Wolff's algorithm. It only requires four simple lines of computer code, and is approximately ten times faster than the Box-Muller algorithm.Comment: 5 pages, 3 encapsulated Postscript Figures. Submitted to Phys.Rev.Letters. For related work, see http://pipe.unizar.es/~jf

Long and short paths in uniform random recursive dags

In a uniform random recursive k-dag, there is a root, 0, and each node in turn, from 1 to n, chooses k uniform random parents from among the nodes of smaller index. If S_n is the shortest path distance from node n to the root, then we determine the constant \sigma such that S_n/log(n) tends to \sigma in probability as n tends to infinity. We also show that max_{1 \le i \le n} S_i/log(n) tends to \sigma in probability.Comment: 16 page

Differences in 5'untranslated regions highlight the importance of translational regulation of dosage sensitive genes

Background: Untranslated regions (UTRs) are important mediators of post-transcriptional regulation. The length of UTRs and the composition of regulatory elements within them are known to vary substantially across genes, but little is known about the reasons for this variation in humans. Here, we set out to determine whether this variation, specifically in 5’UTRs, correlates with gene dosage sensitivity. Results: We investigate 5’UTR length, the number of alternative transcription start sites, the potential for alternative splicing, the number and type of upstream open reading frames (uORFs) and the propensity of 5’UTRs to form secondary structures. We explore how these elements vary by gene tolerance to loss-of-function (LoF; using the LOEUF metric), and in genes where changes in dosage are known to cause disease. We show that LOEUF correlates with 5’UTR length and complexity. Genes that are most intolerant to LoF have longer 5’UTRs, greater TSS diversity, and more upstream regulatory elements than their LoF tolerant counterparts. We show that these differences are evident in disease gene-sets, but not in recessive developmental disorder genes where LoF of a single allele is tolerated. Conclusions: Our results confirm the importance of post-transcriptional regulation through 5'UTRs in tight regulation of mRNA and protein levels, particularly for genes where changes in dosage are deleterious and lead to disease. Finally, to support gene-based investigation we release a web-based browser tool, VuTR, that supports exploration of the composition of individual 5'UTRs and the impact of genetic variation within them

Risk of criminal justice system interactions in young adults with attention-deficit/hyperactivity disorder: findings from a national birth cohort

Objective: To examine criminal justice system (CJS) interactions and pathways through the justice system for young adults with ADHD compared to young adults without ADHD. Method: Nationwide 3-year birth cohort study using linked health and CJS data. Cox proportional hazards models were employed to examine associations between ADHD and police proceedings, court charges, court convictions, and incarcerations. Results: Young adults with ADHD were significantly more likely to interact with the CJS including police proceedings (hazard ratio [HR], 2.1 95% CI [2.0, 2.2]) court charges (HR, 2.2 95% CI [2.1, 2.3]), court convictions (HR, 2.3 95% CI [2.2, 2.4]), and incarceration (HR, 4.8 95% CI [4.3, 5.4]). Conclusions: Young adults with ADHD are overrepresented at all stages of the CJS. Results highlight the importance of early identification and responsivity to ADHD within the CJS and suggest that the NZ justice system may require changes to both areas to ensure that young individuals with ADHD receive equitable access to, and treatment within, the CJS

Domino-like transient dynamics at seizure onset in epilepsy

This is the final version. Available on open access from Public Library of Science via the DOI in this recordData Availability: We have made publicly available the 15 epochs of human EEG data containing generalized paroxysms classified as focal onset, and all 15 epochs containing seizures from one individual used in the manuscript, 1252 EEG epochs containing seizures classified as generalized onset and the 6 mouse mEC recordings. All data and the code used for the data analysis and model simulations they can be accessed via DOI 10.17605/OSF.IO/G2EXK.The International League Against Epilepsy (ILAE) groups seizures into “focal”, “generalized” and “unknown” based on whether the seizure onset is confined to a brain region in one hemisphere, arises in several brain region simultaneously, or is not known, respectively. This separation fails to account for the rich diversity of clinically and experimentally observed spatiotemporal patterns of seizure onset and even less so for the properties of the brain networks generating them. We consider three different patterns of domino-like seizure onset in Idiopathic Generalized Epilepsy (IGE) and present a novel approach to classification of seizures. To understand how these patterns are generated on networks requires understanding of the relationship between intrinsic node dynamics and coupling between nodes in the presence of noise, which currently is unknown. We investigate this interplay here in the framework of domino-like recruitment across a network. In particular, we use a phenomenological model of seizure onset with heterogeneous coupling and node properties, and show that in combination they generate a range of domino-like onset patterns observed in the IGE seizures. We further explore the individual contribution of heterogeneous node dynamics and coupling by interpreting in-vitro experimental data in which the speed of onset can be chemically modulated. This work contributes to a better understanding of possible drivers for the spatiotemporal patterns observed at seizure onset and may ultimately contribute to a more personalized approach to classification of seizure types in clinical practice.Engineering and Physical Sciences Research Council (EPSRC)Medical Research Council (MRC