Parent initiated prednisolone for acute asthma in children of school age : randomised controlled crossover trial

Objective To evaluate the efficacy of a short course of parent initiated oral prednisolone for acute asthma in children of school age.

Design Double blind, randomised, placebo controlled, crossover trial in which episodes of asthma, rather than participants, were randomised to treatment.

Setting The Barwon region of Victoria, Australia.

Participants Children aged 5-12 years with a history of recurrent episodes of acute asthma.

Intervention A short course of parent initiated treatment with prednisolone (1 mg/kg a day) or placebo.

Main outcome measures The primary outcome measure was the mean daytime symptom score over seven days. Secondary outcome measures were mean night time symptom score over seven days, use of health resources, and school absenteeism.

Results 230 children were enrolled in the study. Over a three year period, 131 (57%) of the participants contributed a total of 308 episodes of asthma that required parent initiated treatment: 155 episodes were treated with parent initiated prednisolone and 153 with placebo. The mean daytime symptom score was 15% lower in episodes treated with prednisolone than in those treated with placebo (geometric mean ratio 0.85, 95% CI 0.74 to 0.98; P=0.023). Treatment with prednisolone was also associated with a 16% reduction in the night time symptom score (geometric mean ratio 0.84, 95% CI 0.70 to 1.00; P=0.050), a reduced risk of health resource use (odds ratio 0.54, 95% CI 0.34 to 0.86; P=0.010), and reduced school absenteeism (mean difference −0.4 days, 95% CI −0.8 to 0.0 days; P=0.045).

Conclusion A short course of oral prednisolone initiated by parents when their child experiences an episode of acute asthma may reduce asthma symptoms, health resource use, and school absenteeism. However, the modest benefits of this strategy must be balanced against potential side effects of repeated short courses of an oral corticosteroid.

The Pharmaceutical Industry and Access to Medicines in India

Pharmaceutical policy in India as elsewhere is shaped by conflicting economic and social interests and opposing values and priorities. Tensions can be understood as revolving around the contradiction between use value and exchange value in the production of medicinal drugs as commodities, as per Marx’s original analysis. The use value of medicines – if safe and efficacious, of good quality, and prescribed and consumed appropriately – is the prevention, cure or alleviation of ill-health and disease. Health policy is – or should be – aimed at optimising the use value of medicines. For this purpose government agencies administer regulatory oversight of the manufacturing, marketing and distribution of medicines. Drugs made available to patients are expected to meet adequate safety, quality and efficacy standards, but regulation to ensure such standards is subject to controversy in most countries. This is a domain where definition and interpretation of scientific-technological principles and criteria is infused by partiality and bias grounded in social and material interests, as evidenced by recurrent debates about industry ‘capture’ of regulatory agencies, including the world’s most regulator, the US Food and Drug Administration (Angell 2005; Law 2006). In India, a Parliamentary Committee Report in 2012 depicted the Central Drugs Standard Control Organisation (CDSCO) as dysfunctional and influenced inappropriately by the exchange value perspective of manufacturers (Parliamentary Standing Committee on Health and Welfare 2012). The clash between use and exchange value perspectives is starkly illustrated by cases of products known to cause more harm than good, particularly common in poorly regulated markets such as India’s, as shown by Srinivasan & Phadke.

Incidence and persistence/recurrence of women’s sexual difficulties : findings from the Australian longitudinal study of health and relationships

This study presents data on the prevalence, incidence, and persistence/recurrence of 8 sexual difficulties among women. Australian women participated in 2 computer-assisted interviews approximately 12 months apart. Analyses were based on a weighted sample of 2,252 women who were 20–64 years of age, sexually active in the past 12 months, and in the same heterosexual relationship at both interviews. Upon recruitment, two-thirds of women (66%) reported having one or more sexual difficulties. At follow-up, 36% reported a new sexual difficulty. The two highest incident difficulties were “lacking interest in having sex” (26%) and “taking too long to orgasm” (11%). In addition, 68% of women with 1 or more sexual difficulties at recruitment reported having at least 1 of these again at follow-up. Lacking interest in having sex had the highest persistence/recurrence (65%). Logistic regression modeling revealed a lower incidence of sexual difficulties among women in their 40s. Age was also a predictor of the persistence/recurrence, with persistence/recurrence most likely among older women. Tobacco and alcohol use predicted the incidence, but not persistence/recurrence, of lacking interest in sex. Health professionals need to take note of the sociodemographic groups most prone to developing and having persistent/recurrent sexual difficulties.

How did this snail get here? Several dispersal vectors inferred for an aquatic invasive species

1. How species reach and persist in isolated habitats remains an open question in many cases, especially for rapidly spreading invasive species. This is particularly true for temporary freshwater ponds, which can be remote and may dry out annually, but may still harbour high biodiversity. Persistence in such habitats depends on recurrent colonisation or species survival capacity, and ponds therefore provide an ideal system to investigate dispersal and connectivity. 2. Here, we test the hypothesis that the wide distributions and invasive potential of aquatic snails is due to their ability to exploit several dispersal vectors in different landscapes. We explored the population structure of Physa acuta (recent synonyms: Haitia acuta, Physella acuta, Pulmonata: Gastropoda), an invasive aquatic snail originating from North America, but established in temporary ponds in Doñana National Park, southern Spain. In this area, snails face land barriers when attempting to colonise other suitable habitat. 3. Genetic analyses using six microsatellite loci from 271 snails in 21 sites indicated that (i) geographically and hydrologically isolated snail populations in the park were genetically similar to a large snail population in rice fields more than 15 km away; (ii) these isolated ponds showed an isolation-by-distance pattern. This pattern broke down, however, for those ponds visited frequently by large mammals such as cattle, deer and wild boar; (iii) snail populations were panmictic in flooded and hydrologically connected rice fields. 4. These results support the notion that aquatic snails disperse readily by direct water connections in the flooded rice fields, can be carried by waterbirds flying between the rice fields and the park and may disperse between ponds within the park by attaching to large mammals. 5. The potential for aquatic snails such as Physa acuta to exploit several dispersal vectors may contribute to their wide distribution on various continents and their success as invasive species. We suggest that the interaction between different dispersal vectors, their relation to specific habitats and consequences at different geographic scales should be considered both when attempting to control invasive freshwater species and when protecting endangered species.

Comparison of optimised MDI versus pumps with or without sensors in severe hypoglycaemia (the Hypo COMPaSS trial)

Background
Severe hypoglycaemia (SH) is one of the most feared complications of type 1 diabetes (T1DM) with a reported prevalence of nearly 40%. In randomized trials of Multiple Daily Injections (MDI) and Continuous Subcutaneous Insulin Infusion (CSII) therapy there is a possible benefit of CSII in reducing SH. However few trials have used basal insulin analogues as the basal insulin in the MDI group and individuals with established SH have often been excluded from prospective studies. In published studies investigating the effect of Real Time Continuous Glucose Monitoring (RT-CGM) benefit in terms of reduced SH has not yet been demonstrated. The primary objective of this study is to elucidate whether in people with T1DM complicated by impaired awareness of hypoglycaemia (IAH), rigorous prevention of biochemical hypoglycaemia using optimized existing self-management technology and educational support will restore awareness and reduce risk of recurrent SH.

Methods/design
This is a multicentre prospective RCT comparing hypoglycaemia avoidance with optimized MDI and CSII with or without RT-CGM in a 2×2 factorial design in people with type 1 diabetes who have IAH. The primary outcome measure for this study is the difference in IAH (Gold score) at 24 weeks. Secondary outcomes include biomedical measures such as HbA1c, SH incidence, blinded CGM analysis, self monitored blood glucose (SMBG) and response to hypoglycaemia in gold standard clamp studies. Psychosocial measures including well-being and quality of life will also be assessed using several validated and novel measures. Analysis will be on an intention-to-treat basis.

Discussion
Most existing RCTs using this study’s interventions have been powered for change in HbA1c rather than IAH or SH. This trial will demonstrate whether IAH can be reversed and SH prevented in people with T1DM in even those at highest risk by using optimized conventional management and existing technology.

A distinct DNA methylation signature defines pediatric pre-B cell acute lymphoblastic leukemia

Pre-B cell acute lymphoblastic leukemia (ALL) is the most prevalent childhood malignancy and remains one of the highest causes of childhood mortality. Despite this, the mechanisms leading to disease remain poorly understood. We asked if recurrent aberrant DNA methylation plays a role in childhood ALL and have defined a genome-scale DNA methylation profile associated with the ETV6-RUNX1 subtype of pediatric ALL. Archival bone marrow smears from 19 children collected at diagnosis and remission were used to derive a disease specific DNA methylation profile. The gene signature was confirmed in an independent cohort of 86 patients. A further 163 patients were analyzed for DNA methylation of a three gene signature. We found that the DNA methylation signature at diagnosis was unique from remission. Fifteen loci were sufficient to discriminate leukemia from disease-free samples and purified CD34+ cells. DNA methylation of these loci was recurrent irrespective of cytogenetic subtype of pre-B cell ALL. We show that recurrent aberrant genomic methylation is a common feature of pre-B ALL, suggesting a shared pathway for disease development. By revealing new DNA methylation markers associated with disease, this study has identified putative targets for development of novel epigenetic-based therapies.

Physical comorbidities in men with mood and anxiety disorders: a population-based study

Background : The mind-body nexus has been a topic of growing interest. Further data are however required to understand the specific relationship between mood and anxiety disorders and individual physical health conditions, and to verify whether these psychiatric disorders are linked to overall medical burden.
Methods : This study examined data collected from 942 men, 20 to 97 years old, participating in the Geelong Osteoporosis Study. A lifetime history of mood and anxiety disorders was identified using the Structured Clinical Interview for DSM-IV-TR Research Version, Non-patient edition (SCID-I/NP). The presence of medical conditions (lifetime) was self-reported and confirmed by medical records, medication use or clinical data. Anthropometric measurements and socioeconomic status (SES) were determined and information on medication use and lifestyle was obtained via questionnaire. Logistic regression models were used to test the associations.
Results : After adjustment for age, socioeconomic status, and health risk factors (body mass index, physical activity and smoking), mood disorders were associated with gastro oesophageal reflux disease (GORD), recurrent headaches, blackouts and/or epilepsy, liver disorders and pulmonary disease in older people, whilst anxiety disorders were significantly associated with thyroid, GORD and other gastrointestinal disorders, and psoriasis. Increased odds of high medical burden were associated with both mood and anxiety disorders.
Conclusions : Our study provides further population-based evidence supporting the link between mental and physical illness in men. Understanding these associations is not only necessary for individual management, but also to inform the delivery of health promotion messages and health care.

Combined joint fusion for index and middle carpometacarpal instability in elite boxers

Isolated instability of the index and middle finger carpometacarpal joints is uncommon. An unpublished injury pattern in a consecutive series of 13 elite boxers is described, with mid-term radiological and functional results of two novel surgical treatments. All the boxers (from Australia and the UK) were unable to compete owing to pain and weakness. Four boxers were managed initially by open reduction and temporary K-wire fixation. Nine boxers underwent primary carpometacarpal arthrodesis. All were able to return to their previous level of competition. One boxer who had undergone a soft tissue reconstruction competed at international level but required an arthrodesis because of recurrent symptoms. In elite boxers, simple reduction and wiring may be appropriate for an acute injury causing index or middle finger carpometacarpal joint instability, however, arthrodesis is the treatment of choice when instability and degenerative changes are present.

A corrosion inhibition study of steel grinding balls in an oxygen and alkaline environment

The corrosion of steel grinding balls is a major recurrent cost for mill operators concerned with the production gold. Subsequently, the use of corrosion inhibitors in production fluids, which is typically at pH >9, is an attractive and economical option. This study reports on the corrosion wear of steel grinding balls under alkaline/oxygen conditions and in presence of cyanide. A fundamental study on the influence of several inorganic-based inhibitors (i.e., nitrite, chromate, silicate, hexametaphosphate) on the corrosion rate of carbon steel was undertaken. Subsequently, the corrosion performances of various inhibitors were evaluated in stirred vessels. Corrosion rates were determined via mass loss and electrochemical methods (i.e., linear polarisation, Tafel). It was observed that inhibitors based upon chromate provide superior protection under the conditions investigated in this study. In lime treated, high chloride waters, chromate gave over 80% protection at levels of 10 100 ppm with no evidence of pitting.

A review of online learning in supervised neural networks

Learning in neural networks can broadly be divided into two categories, viz., off-line (or batch) learning and online (or incremental) learning. In this paper, a review of a variety of supervised neural networks with online learning capabilities is presented. Specifically, we focus on articles published in main indexed journals in the past 10 years (2003–2013). We examine a number of key neural network architectures, which include feedforward neural networks, recurrent neural networks, fuzzy neural networks, and other related networks. How the online learning methodologies are incorporated into these networks is exemplified, and how they are applied to solving problems in different domains is highlighted. A summary of the review that covers different network architectures and their applications is presented.

A high performance position sensorless surface permanent magnet synchronous motor drive based on flux angle

A position sensorless Surface Permanent Magnet Synchronous Motor (SPMSM) drive based on flux angle is presented in this paper. The motor equations are written in rotor fixed d-q reference frame. A PID controller is used to process the speed error to generate the reference torque current keeping the magnetizing current fixed. The estimated stator flux using Recurrent Neural Network (RNN) is used to find out the rotor position. The flux angle and the reference current phasor angle are used in vector rotator to generate the reference phase currents. Hysteresis current controller block controls the switching of the 3-phase inverter to apply voltage to the motor stator. Simulation studies on different operating conditions indicate the acceptability of the drive system. The drive system only requires a speed transducer and is free from position sensor requirement. The proposed control scheme is robust under load torque disturbances and motor parameter variations. It is also simple and low cost to implement in a practical environment.

Genetic algorithm based PI controller tuning for induction motor drive with ANN flux estimator

This paper presents a Genetic Algorithm (GA) based fast speed response controller for poly-phase induction motor drive. Here the proportional and integral gains of PI controller are optimized by GA to achieve quick speed response. An adaptive Recurrent Neural Network (RNN) with Real Time Recurrent Learning (RTRL) algorithm is proposed to estimate rotor flux. An online tuning scheme to update the weight of RNN is presented to overcome stator resistance variation problem. This tuning scheme requires torque estimator to calculate the torque error. Space vector modulation (SVM) technique is used to produce the motor input voltage. Simulation tests have been performed to study the dynamic performances of the drive system for both the classical PI and the genetic algorithm based PI controllers.

Three algorithms for learning artificial neural network: A comparison for induction motor flux estimation

This paper presents a comparative study of three algorithms for learning artificial neural network. As neural estimator, back-propagation (BP) algorithm, uncorrelated real time recurrent learning (URTRL) algorithm and correlated real time recurrent learning (CRTRL) algorithm are used in the present work to learn the artificial neural network (ANN). The approach proposed here is based on the flux estimation of high performance induction motor drives. Simulation of the drive system was carried out to study the performance of the motor drive. It is observed that the proposed CRTRL algorithm based methodology provides better performance than the BP and URTRL algorithm based technique. The proposed method can be used for accurate measurement of the rotor flux.

Vector control of a position sensorless SPMSM drive with RNN based stator flux estimator

A position sensorless Surface Permanent Magnet Synchronous Motor (SPMSM) drive based on single layer Recurrent Neural Network (RNN) is presented in this paper. The motor equations are written in rotor fixed d-q reference frame. A PID controller is used to process the speed error to generate the reference torque current keeping the magnetizing current fixed. The RNN estimator is used to estimate flux components along the stator fixed stationary axes. The flux angle and the reference current phasor angle are used in vector rotator to generate the reference phase currents. Hysteresis current controller block controls the switching of the three phase inverter to apply voltage to the motor stator. Simulation studies on different operating conditions indicate the acceptability of the drive system. The proposed estimator can be used to accurately measure the motor fluxes and rotor angle over a wide speed range. The proposed control scheme is robust under load torque disturbances and motor parameter variations. It is also simple and low cost to implememnt in a practical environment

Characteristics and outcomes of patients requiring rapid response system activation within 24 hours of emergency admission

Objectives: