Prospectively Collected Characteristics of Adult Patients, Their Consultations and Outcomes as They Report Breathlessness When Presenting to General Practice in Australia

Introduction:Breathlessness is a subjective sensation, so understanding its impacts requires patients' reports, including prospective patient-defined breathlessness as a reason for presenting to general practitioners (GP).The aim of this study was to define the prevalence of breathlessness as a reason for GP consultations while defining the clinico-demographic factors of these patients and the characteristics and outcomes of those consultations.Methods:Using nine years of the Family Medicine Research Centre database of 100 consecutive encounters from 1,000 practices annually, the patient-defined reason for encounter 'breathlessness' was explored using prospectively collected data in people ≥18 years with clinical data coded using the International Classification for Primary Care V2. Dichotomous variables were analysed using chi square and 95% confidence intervals calculated using Kish's formula for a single stage clustered design.Results:Of all the 755,729 consultations collected over a nine year period from 1 April, 2000, 7255 included breathlessness as a reason for encounter (0.96%; 95% CI 0.93 to 0.99) most frequently attributed to chronic obstructive pulmonary disease. Only 48.3% of GPs saw someone reporting breathlessness. The proportion of consultations with breathlessness increased with age. Breathlessness trebled the likelihood that the consultation occurred in the community rather than the consulting room (p<0.0001) and increased 2.5 fold the likelihood of urgent referral to hospital (p<0.0001). Of those with breathlessness, 12% had undiagnosed breathlessness at the end of the consultation (873/7255) with higher likelihood of being younger females.Discussion:Breathlessness is a prevalent symptom in general practitioner. Such prevalence enables future research focused on understanding the temporal pattern of breathlessness and the longitudinal care offered to, and outcomes for these patients, including those who leave the consultation without a diagnosis. © 2013 Currow et al

Differential expression analysis for sequence count data

*Motivation:* High-throughput nucleotide sequencing provides quantitative readouts in assays for RNA expression (RNA-Seq), protein-DNA binding (ChIP-Seq) or cell counting (barcode sequencing). Statistical inference of differential signal in such data requires estimation of their variability throughout the dynamic range. When the number of replicates is small, error modelling is needed to achieve statistical power.&#xd;&#xa;&#xd;&#xa;*Results:* We propose an error model that uses the negative binomial distribution, with variance and mean linked by local regression, to model the null distribution of the count data. The method controls type-I error and provides good detection power. &#xd;&#xa;&#xd;&#xa;*Availability:* A free open-source R software package, _DESeq_, is available from the Bioconductor project and from &#x22;http://www-huber.embl.de/users/anders/DESeq&#x22;:http://www-huber.embl.de/users/anders/DESeq

Exploring the measurement of markedness and its relationship with other linguistic variables

Antonym pair members can be differentiated by each word's markedness-that distinction attributable to the presence or absence of features at morphological or semantic levels. Morphologically marked words incorporate their unmarked counterpart with additional morphs (e.g., "unlucky" vs. "lucky"); properties used to determine semantically marked words (e.g., "short" vs. "long") are less clearly defined. Despite extensive theoretical scrutiny, the lexical properties of markedness have received scant empirical study. The current paper employs an antonym sequencing approach to measure markedness: establishing markedness probabilities for individual words and evaluating their relationship with other lexical properties (e.g., length, frequency, valence). Regression analyses reveal that markedness probability is, as predicted, related to affixation and also strongly related to valence. Our results support the suggestion that antonym sequence is reflected in discourse, and further analysis demonstrates that markedness probabilities, derived from the antonym sequencing task, reflect the ordering of antonyms within natural language. In line with the Pollyanna Hypothesis, we argue that markedness is closely related to valence; language users demonstrate a tendency to present words evaluated positively ahead of those evaluated negatively if given the choice. Future research should consider the relationship of markedness and valence, and the influence of contextual information in determining which member of an antonym pair is marked or unmarked within discourse

Shrinking wings for ultrasonic pitch production: hyperintense ultra-short-wavelength calls in a new genus of neotropical katydids (Orthoptera: tettigoniidae)

This article reports the discovery of a new genus and three species of predaceous katydid (Insecta: Orthoptera) from Colombia and Ecuador in which males produce the highest frequency ultrasonic calling songs so far recorded from an arthropod. Male katydids sing by rubbing their wings together to attract distant females. Their song frequencies usually range from audio (5 kHz) to low ultrasonic (30 kHz). However, males of Supersonus spp. call females at 115 kHz, 125 kHz, and 150 kHz. Exceeding the human hearing range (50 Hz–20 kHz) by an order of magnitude, these insects also emit their ultrasound at unusually elevated sound pressure levels (SPL). In all three species these calls exceed 110 dB SPL rms re 20 µPa (at 15 cm). Males of Supersonus spp. have unusually reduced forewings (<0.5 mm2). Only the right wing radiates appreciable sound, the left bears the file and does not show a particular resonance. In contrast to most katydids, males of Supersonus spp. position and move their wings during sound production so that the concave aspect of the right wing, underlain by the insect dorsum, forms a contained cavity with sharp resonance. The observed high SPL at extreme carrier frequencies can be explained by wing anatomy, a resonant cavity with a membrane, and cuticle deformation

Procalcitonin and Interleukin-10 May Assist in Early Prediction of Bacteraemia in Children With Cancer and Febrile Neutropenia

ObjectivesFebrile neutropenia (FN) causes treatment disruption and unplanned hospitalization in children with cancer. Serum biomarkers are infrequently used to stratify these patients into high or low risk for serious infection. This study investigated plasma abundance of cytokines in children with FN and their ability to predict bacteraemia.MethodsThirty-three plasma cytokines, C-reactive protein (CRP) and procalcitonin (PCT) were measured using ELISA assays in samples taken at FN presentation (n = 79) and within 8-24 h (Day 2; n = 31). Optimal thresholds for prediction of bacteraemia were identified and the predictive ability of biomarkers in addition to routinely available clinical variables was assessed.ResultsThe median age of included FN episodes was 6.0 years and eight (10%) had a bacteraemia. On presentation, elevated PCT, IL-10 and Mip1-beta were significantly associated with bacteraemia, while CRP, IL-6 and IL-8 were not. The combination of PCT (≥0.425 ng/ml) and IL-10 (≥4.37 pg/ml) had a sensitivity of 100% (95% CI 68.8-100%) and specificity of 89% (95% CI 80.0-95.0%) for prediction of bacteraemia, correctly identifying all eight bacteraemia episodes and classifying 16 FN episodes as high-risk. There was limited additive benefit of incorporating clinical variables to this model. On Day 2, there was an 11-fold increase in PCT in episodes with a bacteraemia which was significantly higher than that observed in the non-bacteraemia episodes.ConclusionElevated PCT and IL-10 accurately identified all bacteraemia episodes in our FN cohort and may enhance the early risk stratification process in this population. Prospective validation and implementation is required to determine the impact on health service utilisation

Identifying differential exon splicing using linear models and correlation coefficients

Background: With the availability of the Affymetrix exon arrays a number of tools have been developed to enable the analysis. These however can be expensive or have several pre-installation requirements. This led us to develop an analysis workflow for analysing differential splicing using freely available software packages that are already being widely used for gene expression analysis. The workflow uses the packages in the standard installation of R and Bioconductor (BiocLite) to identify differential splicing. We use the splice index method with the LIMMA framework. The main drawback with this approach is that it relies on accurate estimates of gene expression from the probe-level data. Methods such as RMA and PLIER may misestimate when a large proportion of exons are spliced. We therefore present the novel concept of a gene correlation coefficient calculated using only the probeset expression pattern within a gene. We show that genes with lower correlation coefficients are likely to be differentially spliced.Results: The LIMMA approach was used to identify several tissue-specific transcripts and splicing events that are supported by previous experimental studies. Filtering the data is necessary, particularly removing exons and genes that are not expressed in all samples and cross-hybridising probesets, in order to reduce the false positive rate. The LIMMA approach ranked genes containing single or few differentially spliced exons much higher than genes containing several differentially spliced exons. On the other hand we found the gene correlation coefficient approach better for identifying genes with a large number of differentially spliced exons.Conclusion: We show that LIMMA can be used to identify differential exon splicing from Affymetrix exon array data. Though further work would be necessary to develop the use of correlation coefficients into a complete analysis approach, the preliminary results demonstrate their usefulness for identifying differentially spliced genes. The two approaches work complementary as they can potentially identify different subsets of genes (single/few spliced exons vs. large transcript structure differences)

Death by request in The Netherlands: facts, the legal context and effects on physicians, patients and families

In this article I intend to describe an issue of the Dutch euthanasia practice that is not common knowledge. After some general introductory descriptions, by way of formulating a frame of reference, I shall describe the effects of this practice on patients, physicians and families, followed by a more philosophical reflection on the significance of these effects for the assessment of the authenticity of a request and the nature of unbearable suffering, two key concepts in the procedure towards euthanasia or physician-assisted suicide. This article does not focus on the arguments for or against euthanasia and the ethical justification of physician-assisted dying. These arguments have been described extensively in Kimsma and Van Leeuwen (Asking to die. Inside the Dutch debate about euthanasia, Kluwer Academic Publishers, Dordrecht, 1998)

Results of the MAJORANA DEMONSTRATOR's Search for Double-Beta Decay of 76Ge to Excited States of 76Se

The MAJORANA DEMONSTRATOR is searching for double-beta decay of 76Ge to excited states (E.S.) in 76Se using a modular array of high purity Germanium detectors. 76Ge can decay into three E.S.s of 76Se. The E.S. decays have a clear event signature consisting of a ββ-decay with the prompt emission of one or two γ-rays, resulting in with high probability in a multi-site event. The granularity of the DEMONSTRATOR detector array enables powerful discrimination of this event signature from backgrounds. Using 21.3 kg-y of isotopic exposure, the DEMONSTRATOR has set world leading limits for each E.S. decay, with 90% CL lower half-life limits in the range of (0.56 2.1) ⋅ 1024 y. In particular, for the 2v transition to the first 0+ E.S. of 76Se, a lower half-life limit of 0.68 ⋅ 1024 at 90% CL was achieved

ADC Nonlinearity Correction for the Majorana Demonstrator

Imperfections in analog-to-digital conversion (ADC) cannot be ignored when signal digitization requirements demand both wide dynamic range and high resolution, as is the case for the Majorana Demonstrator 76Ge neutrinoless double-beta decay search. Enabling the experiment's high-resolution spectral analysis and efficient pulse shape discrimination required careful measurement and correction of ADC nonlinearities. A simple measurement protocol was developed that did not require sophisticated equipment or lengthy data-taking campaigns. A slope-dependent hysteresis was observed and characterized. A correction applied to digitized waveforms prior to signal processing reduced the differential and integral nonlinearities by an order of magnitude, eliminating these as dominant contributions to the systematic energy uncertainty at the double-beta decay Q value

Effect of closed endotracheal suction in high-frequency ventilated premature infants measured with electrical impedance tomography

Objective: To determine the global and regional changes in lung volume during and after closed endotracheal tube (ETT) suction in high-frequency ventilated preterm infants with respiratory distress syndrome (RDS). Design: Prospective observational clinical study. Setting: Neonatal intensive care unit. Patients: Eleven non-muscle relaxed preterm infants with RDS ventilated with open lung high-frequency ventilation (HFV). Interventions: Closed ETT suction. Measurements and results: Changes in global and regional lung volume were measured with electrical impedance tomography. ETT suction resulted in an acute loss of lung volume followed by spontaneous recovery with a median residual loss of 3.3% of the maximum volume loss. The median stabilization time was 8 s. At the regional level, the lung volume changes during and after ETT suction were heterogeneous in nature. Conclusions: Closed ETT suction causes an acute, transient and heterogeneous loss of lung volume in premature infants with RDS treated with open lung HFV