Normal limits for oscillometric bronchodilator responses and relationships with clinical factors.

Introduction: We aimed to determine normal thresholds for positive bronchodilator responses for oscillometry in an Australian general population sample aged ≥40 years, to guide clinical interpretation. We also examined relationships between bronchodilator responses and respiratory symptoms, asthma diagnosis, smoking and baseline lung function. Methods: Subjects recruited from Sydney, Melbourne and Busselton, Australia, underwent measurements of spirometry, resistance (R rs6 ) and reactance (X rs6 ) at 6 Hz, before and after inhalation of salbutamol 200 μg. Respiratory symptoms and/or medication use, asthma diagnosis, and smoking were recorded. Threshold bronchodilator responses were defined as the fifth percentile of decrease in R rs6 and 95th percentile increase in X rs6 in a healthy subgroup. Results: Of 1318 participants, 1145 (570 female) were analysed. The lower threshold for ΔR rs6 was -1.38 cmH2O·s·L-1 (-30.0% or -1.42 Z-scores) and upper threshold for ΔX rs6 was 0.57 cmH2O·s·L-1 (1.36 Z-scores). Respiratory symptoms and/or medication use, asthma diagnosis, and smoking all predicted bronchodilator response, as did baseline oscillometry and spirometry. When categorised into clinically relevant groups according to those predictors, ΔX rs6 was more sensitive than spirometry in smokers without current asthma or chronic obstructive pulmonary disease (COPD), ∼20% having a positive response. Using absolute or Z-score change provided similar prevalences of responsiveness, except in COPD, in which responsiveness measured by absolute change was twice that for Z-score. Discussion: This study describes normative thresholds for bronchodilator responses in oscillometry parameters, including intra-breath parameters, as determined by absolute, relative and Z-score changes. Positive bronchodilator response by oscillometry correlated with clinical factors and baseline function, which may inform the clinical interpretation of oscillometry

How well do adolescents recall use of mobile telephones? Results of a validation study

<p>Abstract</p> <p>Background</p> <p>In the last decade mobile telephone use has become more widespread among children. Concerns expressed about possible health risks have led to epidemiological studies investigating adverse health outcomes associated with mobile telephone use. Most epidemiological studies have relied on self reported questionnaire responses to determine individual exposure. We sought to validate the accuracy of self reported adolescent mobile telephone use.</p> <p>Methods</p> <p>Participants were recruited from year 7 secondary school students in Melbourne, Australia. Adolescent recall of mobile telephone use was assessed using a self administered questionnaire which asked about number and average duration of calls per week. Validation of self reports was undertaken using Software Modified Phones (SMPs) which logged exposure details such as number and duration of calls.</p> <p>Results</p> <p>A total of 59 adolescents participated (39% boys, 61% girls). Overall a modest but significant rank correlation was found between self and validated number of voice calls (ρ = 0.3, P = 0.04) with a sensitivity of 57% and specificity of 66%. Agreement between SMP measured and self reported duration of calls was poorer (ρ = 0.1, P = 0.37). Participants whose parents belonged to the 4^thsocioeconomic stratum recalled mobile phone use better than others (ρ = 0.6, P = 0.01).</p> <p>Conclusion</p> <p>Adolescent recall of mobile telephone use was only modestly accurate. Caution is warranted in interpreting results of epidemiological studies investigating health effects of mobile phone use in this age group.</p

Kernel bandwidth optimization in spike rate estimation

Kernel smoother and a time-histogram are classical tools for estimating an instantaneous rate of spike occurrences. We recently established a method for selecting the bin width of the time-histogram, based on the principle of minimizing the mean integrated square error (MISE) between the estimated rate and unknown underlying rate. Here we apply the same optimization principle to the kernel density estimation in selecting the width or “bandwidth” of the kernel, and further extend the algorithm to allow a variable bandwidth, in conformity with data. The variable kernel has the potential to accurately grasp non-stationary phenomena, such as abrupt changes in the firing rate, which we often encounter in neuroscience. In order to avoid possible overfitting that may take place due to excessive freedom, we introduced a stiffness constant for bandwidth variability. Our method automatically adjusts the stiffness constant, thereby adapting to the entire set of spike data. It is revealed that the classical kernel smoother may exhibit goodness-of-fit comparable to, or even better than, that of modern sophisticated rate estimation methods, provided that the bandwidth is selected properly for a given set of spike data, according to the optimization methods presented here

Inner Speech during Silent Reading Reflects the Reader's Regional Accent

While reading silently, we often have the subjective experience of inner speech. However, there is currently little evidence regarding whether this inner voice resembles our own voice while we are speaking out loud. To investigate this issue, we compared reading behaviour of Northern and Southern English participants who have differing pronunciations for words like ‘glass’, in which the vowel duration is short in a Northern accent and long in a Southern accent. Participants' eye movements were monitored while they silently read limericks in which the end words of the first two lines (e.g., glass/class) would be pronounced differently by Northern and Southern participants. The final word of the limerick (e.g., mass/sparse) then either did or did not rhyme, depending on the reader's accent. Results showed disruption to eye movement behaviour when the final word did not rhyme, determined by the reader's accent, suggesting that inner speech resembles our own voice

Pre-referral rectal artesunate in severe malaria: flawed trial

<p>Abstract</p> <p>Background</p> <p>Immediate injectable treatment is essential for severe malaria. Otherwise, the afflicted risk lifelong impairment or death. In rural areas of Africa and Asia, appropriate care is often miles away. In 2009, Melba Gomes and her colleagues published the findings of a randomized, placebo-controlled trial of rectal artesunate for suspected severe malaria in such remote areas. Enrolling nearly 18,000 cases, the aim was to evaluate whether, as patients were in transit to a health facility, a pre-referral artesunate suppository blocked disease progression sufficiently to reduce these risks. The affirmative findings of this, the only trial on the issue thus far, have led the WHO to endorse rectal artesunate as a pre-referral treatment for severe malaria. In the light of its public health importance and because its scientific quality has not been assessed for a systematic review, our paper provides a detailed evaluation of the design, conduct, analysis, reporting, and practical features of this trial.</p> <p>Results</p> <p>We performed a checklist-based and an in-depth evaluation of the trial. The evaluation criteria were based on the CONSORT statement for reporting clinical trials, the clinical trial methodology literature, and practice in malaria research. Our main findings are: The inclusion and exclusion criteria and the sample size justification are not stated. Many clearly ineligible subjects were enrolled. The training of the recruiters does not appear to have been satisfactory. There was excessive between center heterogeneity in design and conduct. Outcome evaluation schedule was not defined, and in practice, became too wide. Large gaps in the collection of key data were evident. Primary endpoints were inconsistently utilized and reported; an overall analysis of the outcomes was not done; analyses of time to event data had major flaws; the stated intent-to-treat analysis excluded a third of the randomized subjects; the design-indicated stratified or multi-variate analysis was not done; many improper subgroups were analyzed in a post-hoc fashion; the analysis and reporting metric was deficient. There are concerns relating to patient welfare at some centers. Exclusion of many cases from data analysis compromised external validity. A bias-controlled reanalysis of available data does not lend support to the conclusions drawn by the authors.</p> <p>Conclusions</p> <p>This trial has numerous serious deficiencies in design, implementation, and methods of data analysis. Interpretation and manner of reporting are wanting, and the applicability of the findings is unclear. The trial conduct could have been improved to better protect patient welfare. The totality of these problems make it a flawed study whose conclusions remain subject to appreciable doubt.</p

Why we need easy access to all data from all clinical trials and how to accomplish it

International calls for registering all trials involving humans and for sharing the results, and sometimes also the raw data and the trial protocols, have increased in recent years. Such calls have come, for example, from the Organization for Economic Cooperation and Development (OECD), the World Health Organization (WHO), the US National Institutes of Heath, the US Congress, the European Commission, the European ombudsman, journal editors, The Cochrane Collaboration, and several funders, for example the UK Medical Research Council, the Wellcome Trust, the Bill and Melinda Gates Foundation and the Hewlett Foundation

Mourning and melancholia revisited: correspondences between principles of Freudian metapsychology and empirical findings in neuropsychiatry

Freud began his career as a neurologist studying the anatomy and physiology of the nervous system, but it was his later work in psychology that would secure his place in history. This paper draws attention to consistencies between physiological processes identified by modern clinical research and psychological processes described by Freud, with a special emphasis on his famous paper on depression entitled 'Mourning and melancholia'. Inspired by neuroimaging findings in depression and deep brain stimulation for treatment resistant depression, some preliminary physiological correlates are proposed for a number of key psychoanalytic processes. Specifically, activation of the subgenual cingulate is discussed in relation to repression and the default mode network is discussed in relation to the ego. If these correlates are found to be reliable, this may have implications for the manner in which psychoanalysis is viewed by the wider psychological and psychiatric communities