Study protocol: the childhood to adolescence transition study (CATS)

Background
Puberty is a multifaceted developmental process that begins in late-childhood with a cascade of endocrine changes that ultimately lead to sexual maturation and reproductive capability. The transition through puberty is marked by an increased risk for the onset of a range of health problems, particularly those related to the control of behaviour and emotion. Early onset puberty is associated with a greater risk of cancers of the reproductive tract and cardiovascular disease. Previous studies have had methodological limitations and have tended to view puberty as a unitary process, with little distinction between adrenarche, gonadarche and linear growth. The Childhood to Adolescence Transition Study (CATS) aims to prospectively examine associations between the timing and stage of the different hormonally-mediated changes, as well as the onset and course of common health and behavioural problems that emerge in the transition from childhood to adolescence. The initial focus of CATS is on adrenarche, the first hormonal process in the pubertal cascade, which begins for most children at around 8 years of age.

Methods/Design
CATS is a longitudinal population-based cohort study. All Grade 3 students (8–9 years of age) from a stratified cluster sample of schools in Melbourne, Australia were invited to take part. In total, 1239 students and a parent/guardian were recruited to participate in the study. Measures are repeated annually and comprise student, parent and teacher questionnaires, and student anthropometric measurements. A saliva sample was collected from students at baseline and will be repeated at later waves, with the primary purpose of measuring hormonal indices of adrenarche and gonadarche.

Discussion
CATS is uniquely placed to capture biological and phenotypic indices of the pubertal process from its earliest manifestations, together with anthropometric measures and assessment of child health and development. The cohort will provide rich detail of the development, lifestyle, external circumstances and health of children during the transition from childhood through to adolescence. Baseline associations between the hormonal measures and measures of mental health and behaviour will initially be examined cross-sectionally, and then in later waves longitudinally. CATS will make a unique contribution to the understanding of adrenarche and puberty in children’s health and development.

The exception to the rule : Retreating ice front makes Bewick's swans Cygnus columbianus bewickii migrate slower in spring than in autumn

In the vast majority of migratory bird species studied so far, spring migration has been found to proceed faster than autumn migration. In spring, selection pressures for rapid migration are purportedly higher, and migratory conditions such as food supply, daylength, and/or wind support may be better than in autumn. In swans, however, spring migration appears to be slower than autumn migration. Based on a comparison of tundra swan Cygnus columbianus tracking data with long-term temperature data from wheather stations, it has previously been suggested that this was due to a capital breeding strategy (gathering resources for breeding during spring migration) and/or to ice cover constraining spring but not autumn migration. Here we directly test the hypothesis that Bewick's swans Cygnus columbianus bewickii follow the ice front in spring, but not in autumn, by comparing three years of GPS tracking data from individual swans with concurrent ice cover data at five important migratory stop-over sites. In general, ice constrained the swans in the middle part of spring migration, but not in the first (no ice cover was present in the first part) nor in the last part. In autumn, the swans migrated far ahead of ice formation, possibly in order to prevent being trapped by an early onset of winter. We conclude that spring migration in swans is slower than autumn migration because spring migration speed is constrained by ice cover. This restriction to spring migration speed may be more common in northerly migrating birds that rely on freshwater resources. © 2013 The Authors.

Youth mental health first aid: a description of the program and an initial evaluation

BACKGROUND: Adolescence is the peak age of onset for mental illness, with half of all people who will ever have a mental illness experiencing their first episode prior to 18 years of age. Early onset of mental illness is a significant predictor for future episodes. However, adolescents and young adults are less likely than the population as a whole to either seek or receive treatment for a mental illness. The knowledge and attitudes of the adults in an adolescent's life may affect whether or not help is sought, and how quickly. In 2007, the Youth Mental Health First Aid Program was launched in Australia with the aim to teach adults, who work with or care for adolescents, the skills needed to recognise the early signs of mental illness, identify potential mental health-related crises, and assist adolescents to get the help they need as early as possible. This paper provides a description of the program, some initial evaluation and an outline of future directions.

METHODS: The program was evaluated in two ways. The first was an uncontrolled trial with 246 adult members of the Australian public, who completed questionnaires immediately before attending the 14 hour course, one month later and six months later. Outcome measures were: recognition of schizophrenia or depression; intention to offer and confidence in offering assistance; stigmatising attitudes; knowledge about adolescent mental health problems and also about the Mental Health First Aid action plan. The second method of evaluation was to track the uptake of the program, including the number of instructors trained across Australia to deliver the course, the number of courses they delivered, and the uptake of the YMHFA Program in other countries.

RESULTS: The uncontrolled trial found improvements in: recognition of schizophrenia; confidence in offering help; stigmatising attitudes; knowledge about adolescent mental health problems and application of the Mental Health First Aid action plan. Most results were maintained at follow-up. Over the first 3 years of this program, a total of 318 instructors were trained to deliver the course and these instructors have delivered courses to 10,686 people across all states and territories in Australia. The program has also spread to Canada, Singapore and England, and will spread to Hong Kong, Sweden and China in the near future.

CONCLUSIONS: Initial evaluation suggests that the Youth Mental Health First Aid course improves participants' knowledge, attitudes and helping behaviour. The program has spread successfully both nationally and internationally.

Which infants with eczema are at risk of food allergy? Results from a population-based cohort

BACKGROUND: The relationship between early onset eczema and food allergy among infants has never been examined in a population-based sample using the gold standard for diagnosis, oral food challenge. OBJECTIVE: We characterised the risk of challenge-proven food allergy among infants with eczema in the general population. METHODS: One-year-old infants (n = 4453 meeting criteria for this analysis) were assessed for history of eczema, received a nurse-administered eczema examination and underwent skin prick testing to peanut, egg and sesame. Those with a detectable wheal to one of the test foods underwent an oral food challenge irrespective of wheal size. The risk of food allergy, stratified by eczema severity and age of onset, was estimated using multivariate logistic regression with population sampling weights. RESULTS: One in five infants with eczema were allergic to peanut, egg white or sesame, compared to one in twenty-five infants without eczema (OR 6.2, 95% CI 4.9, 7.9, P < 0.001). The prevalence of peanut allergy was low in the absence of eczema (0.7% 95% CI 0.4, 1.1). Infants with eczema were 11.0 times more likely to develop peanut allergy (95% CI 6.6, 18.6) and 5.8 times more likely to develop egg allergy (95% CI 4.6, 7.4) by 12 months than infants without eczema. 50.8% of infants (95% CI 42.8, 58.9) with early eczema onset (<3 months) who required doctor-prescribed topical corticosteroid treatment developed challenge-proven food allergy. CONCLUSION AND CLINICAL RELEVANCE: Eczema, across the clinical severity spectrum in infancy, is a strong risk factor for IgE-mediated food allergy. Infants with eczema were six times more likely to have egg allergy and 11 times more likely to have peanut allergy by 12 months than infants without eczema. Our data suggest that a heightened awareness of food allergy risk among healthcare practitioners treating infants with eczema, especially if early onset and severe, is warranted.

Developmental trajectories of adolescent cannabis use and their relationship to young adult social and behavioural adjustment: a longitudinal study of Australian youth

This study aimed to identify distinct developmental trajectories (sub-groups of individuals who showed similar longitudinal patterns) of cannabis use among Australian adolescents, and to examine associations between trajectory group membership and measures of social and behavioural adjustment in young adulthood. Participants (n=852, 53% female) were part of the International Youth Development Study. Latent class growth analysis was used to identify distinct trajectories of cannabis use frequency from average ages 12 to 19, across 6 waves of data. Logistic regression analyses and analyses of covariance were used to examine relationships between trajectory group membership and young adult (average age: 21) adjustment, controlling for a range of covariates. Three trajectories were identified: abstainers (62%), early onset users (11%), and late onset occasional users (27%). The early onset users showed a higher frequency of antisocial behaviour, violence, cannabis use, cannabis-related harms, cigarette use, and alcohol harms, compared to the abstinent group in young adulthood. The late onset occasional users reported a higher frequency of cannabis use, cannabis-related harms, illicit drug use, and alcohol harms, compared to the abstinent group in young adulthood. There were no differences between the trajectory groups on measures of employment, school completion, post-secondary education, income, depression/anxiety, or alcohol use problems. In conclusion, early onset of cannabis use, even at relatively low frequency during adolescence, is associated with poorer adjustment in young adulthood. Prevention and intervention efforts to delay or prevent uptake of cannabis use should be particularly focussed on early adolescence prior to age 12.

Qualitative assessment of bubble behaviour for central and asymmetric injection in 2D gas-solid fluidized bed using image analysis technique and CFD modelling

Bubble characteristics such as shape, size, and trajectory control the hydrodynamics and therefore heat transfer in fluidized bed reactors. Thus understanding these characteristics is very important for the design and scaleup of fluidized beds. An earlier developed Eulerian-Eulerian two-fluid model for simulating dense gas–solid two-phase flow has been used to compare the experimental data in a pseudo-two-dimensional (2-D) bed. Bubbles are injected asymmetrically by locating the nozzle at proximity to the wall, thus presenting the effect wall has on asymmetrical injection as compared to symmetrical injection. In this work, a digital image analysis technique was developed to study the bubble behaviour in a two-dimensional bubbling bed. The high-speed photography reveals an asymmetric wake formation during detachment indicating an early onset of mixing process. The wall forces acts tangentially on thebubble and has a significant impact on the bubble shape, neck formation during detachment and its trajectory through the bed. Larger bubbles drifting away from the centre with longer paths are observed. This qualitative behaviour is well predicted by CFD modelling. Asymmetric injection can significantly influence the heat and mass transfer characteristics.

Health systems change in 2010

Whilst health science, epidemiology and public health developments have forged enormous progress in understanding, prevention and cure in the health care area we still appear to lack the motivation to tackle the fundamental antecedents of many of our emerging population-based community health problems; the prevention of chronic illness being a prime example.

In spite of much progress in the area of health science, the social, economic and evolutionary forces that cast our physical being in the world still remain poorly understood or accepted in the health care arena. However, if our health care systems are to be manageable and sustainable in the future, these wider antecedents of our health status and wellbeing must be factored more fundamentally in to our management models with more effort being put into preventing lifestyle related chronic illnesses than is currently the case.

As in the past where public health infrastructure innovations such as running water and efficient waste disposal systems served to add greatly to the wellbeing of individuals and communities, we now need to make similar efforts to control preventable illnesses such as metabolic syndrome, type 2 diabetes and lifestyle related cardio-vascular disease at their source rather than waiting until the manifestation of these conditions require major medical and chemical intervention and management before we act. Our young people are at risk of early onset chronic conditions as a result of their emerging sedentary lifestyles, un-healthy dietary habits and health related behaviours, yet we continue to concentrate our health management effort on managing those with existing chronic conditions while leaving younger generations with lifestyle practices and behaviours that pre-dispose individuals to developing chronic illness earlier and earlier in their lives.

It is time we took notice of these emerging trends and began expending more effort to prevent what are essentially lifestyle related illnesses that can be eliminated before they become endemic. By concentrating more upon the social and environmental factors affecting our illness profiles as well as upon dealing more effectively with those who are already suffering from chronic illness we will reduce the need for major end-stage interventions and alleviate the impact and cost of early onset chronic disease. To achieve this new population health vision in Australia at least, we will not only need to utilize the new government funding structures more effectively; those structures that support coordination and more effective management of care, but also take a much broader, environmental and social view of cause and effect in relation to the health of populations.

Immune biomarkers in the spectrum of childhood noncommunicable diseases

A biomarker is an accurately and reproducibly quantifiable biological characteristic that provides an objective measure of health status or disease. Benefits of biomarkers include identification of therapeutic targets, monitoring of clinical interventions, and development of personalized (or precision) medicine. Challenges to the use of biomarkers include optimizing sample collection, processing and storage, validation, and often the need for sophisticated laboratory and bioinformatics approaches. Biomarkers offer better understanding of disease processes and should benefit the early detection, treatment, and management of multiple noncommunicable diseases (NCDs). This review will consider the utility of biomarkers in patients with allergic and other immune-mediated diseases in childhood. Typically, biomarkers are used currently to provide mechanistic insight or an objective measure of disease severity, with their future role in risk stratification/disease prediction speculative at best. There are many lessons to be learned from the biomarker strategies used for cancer in which biomarkers are in routine clinical use and industry-wide standardized approaches have been developed. Biomarker discovery and validation in children with disease lag behind those in adults; given the early onset and therefore potential lifelong effect of many NCDs, there should be more studies incorporating cohorts of children. Many pediatric biomarkers are at the discovery stage, with a long path to evaluation and clinical implementation. The ultimate challenge will be optimization of prevention strategies that can be implemented in children identified as being at risk of an NCD through the use of biomarkers.

The impact of retained austenite characteristics on the two-body abrasive wear behavior of ultrahigh strength bainitic steels

In the current study, a high-carbon, high-alloy steel (0.79 pct C, 1.5 pct Si, 1.98 pct Mn, 0.98 pct Cr, 0.24 pct Mo, 1.06 pct Al, and 1.58 pct Co in wt pct) was subjected to an isothermal bainitic transformation at a temperature range of 473 K to 623 K (200 °C to 350 °C), resulting in different fully bainitic microstructures consisting of bainitic ferrite and retained austenite. With a decrease in the transformation temperature, the microstructure was significantly refined from ~300 nm at 623 K (350 °C) to less than 60 nm at 473 K (200 °C), forming nanostructured bainitic microstructure. In addition, the morphology of retained austenite was progressively altered from film + blocky to an exclusive film morphology with a decrease in the temperature. This resulted in an enhanced wear resistance in nanobainitic microstructures formed at low transformation temperature, e.g., 473 K (200 °C). Meanwhile, it gradually deteriorated with an increase in the phase transformation temperature. This was mostly attributed to the retained austenite characteristics (i.e., thin film vs blocky), which significantly altered their mechanical stability. The presence of blocky retained austenite at high transformation temperature, e.g., 623 K (350 °C) resulted in an early onset of TRIPing phenomenon during abrasion. This led to the formation of coarse martensite with irregular morphology, which is more vulnerable to crack initiation and propagation than that of martensite formed from the thin film austenite, e.g., 473 K (200 °C). This resulted in a pronounced material loss for the fully bainitic microstructures transformed at high temperature, e.g., 623 K (350 °C), leading to distinct sub-surface layer and friction coefficient curve characteristics. A comparison of the abrasive behavior of the fully bainitic microstructure formed at 623 K (350 °C) and fully pearlitic microstructure demonstrated a detrimental effect of blocky retained austenite with low mechanical stability on the two-body abrasion.

Influence of light exposure during early life on the age of onset of bipolar disorder

BACKGROUND: Environmental conditions early in life may imprint the circadian system and influence response to environmental signals later in life. We previously determined that a large springtime increase in solar insolation at the onset location was associated with a younger age of onset of bipolar disorder, especially with a family history of mood disorders. This study investigated whether the hours of daylight at the birth location affected this association. METHODS: Data collected previously at 36 collection sites from 23 countries were available for 3896 patients with bipolar I disorder, born between latitudes of 1.4 N and 70.7 N, and 1.2 S and 41.3 S. Hours of daylight variables for the birth location were added to a base model to assess the relation between the age of onset and solar insolation. RESULTS: More hours of daylight at the birth location during early life was associated with an older age of onset, suggesting reduced vulnerability to the future circadian challenge of the springtime increase in solar insolation at the onset location. Addition of the minimum of the average monthly hours of daylight during the first 3 months of life improved the base model, with a significant positive relationship to age of onset. Coefficients for all other variables remained stable, significant and consistent with the base model. CONCLUSIONS: Light exposure during early life may have important consequences for those who are susceptible to bipolar disorder, especially at latitudes with little natural light in winter. This study indirectly supports the concept that early life exposure to light may affect the long term adaptability to respond to a circadian challenge later in life.

Economic evaluation plan (EEP) for a very early rehabilitation trial (AVERT): an international trial to compare the costs and cost-effectiveness of commencing out of bed standing and walking training (very early mobilization) within 24 h of stroke onset

RATIONALE: A key objective of A Very Early Rehabilitation Trial is to determine if the intervention, very early mobilisation following stroke, is cost-effective. Resource use data were collected to enable an economic evaluation to be undertaken and a plan for the main economic analyses was written prior to the completion of follow up data collection. AIM AND HYPOTHESIS: To report methods used to collect resource use data, pre-specify the main economic evaluation analyses and report other intended exploratory analyses of resource use data. SAMPLE SIZE ESTIMATES: Recruitment to the trial has been completed. A total of 2,104 participants from 56 stroke units across three geographic regions participated in the trial. METHODS AND DESIGN: Resource use data were collected prospectively alongside the trial using standardised tools. The primary economic evaluation method is a cost-effectiveness analysis to compare resource use over 12 months with health outcomes of the intervention measured against a usual care comparator. A cost-utility analysis is also intended. STUDY OUTCOME: The primary outcome in the cost-effectiveness analysis will be favourable outcome (modified Rankin Scale score 0-2) at 12 months. Cost-utility analysis will use health-related quality of life, reported as quality-adjusted life years gained over a 12 month period, as measured by the modified Rankin Scale and the Assessment of Quality of Life. DISCUSSION: Outcomes of the economic evaluation analysis will inform the cost-effectiveness of very early mobilisation following stroke when compared to usual care. The exploratory analysis will report patterns of resource use in the first year following stroke.

Efficacy and safety of very early mobilisation within 24 h of stroke onset (AVERT): a randomised controlled trial

Background Early mobilisation after stroke is thought to contribute to the eff ects of stroke-unit care; however, the intervention is poorly defined and not underpinned by strong evidence. We aimed to compare the effectiveness of frequent, higher dose, very early mobilisation with usual care after stroke.MethodsWe did this parallel-group, single-blind, randomised controlled trial at 56 acute stroke units in five countries. Patients (aged ≥18 years) with ischaemic or haemorrhagic stroke, first or recurrent, who met physiological criteriawere randomly assigned (1:1), via a web-based computer generated block randomisation procedure (block size of six), to receive usual stroke-unit care alone or very early mobilisation in addition to usual care. Treatment with recombinant tissue plasminogen activator was allowed. Randomisation was stratified by study site and stroke severity. Patients, outcome assessors, and investigators involved in trial and data management were masked to treatment allocation. The primary outcome was a favourable outcome 3 months after stroke, defined as a modified Rankin Scale score of 0–2. We did analysis on an intention-to-treat basis. The trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12606000185561.FindingsBetween July 18, 2006, and Oct 16, 2014, we randomly assigned 2104 patients to receive either very early mobilisation (n=1054) or usual care (n=1050); 2083 (99%) patients were included in the 3 month follow-up assessment. 965 (92%) patients were mobilised within 24 h in the very early mobilisation group compared with 623 (59%) patients in the usual care group. Fewer patients in the very early mobilisation group had a favourable outcome than those in the usual care group (n=480 [46%] vs n=525 [50%]; adjusted odds ratio [OR] 0·73, 95% CI 0·59–0·90; p=0·004). 88 (8%) patients died in the very early mobilisation group compared with 72 (7%) patients in the usual care group (OR 1·34, 95% CI 0·93–1·93, p=0·113). 201 (19%) patients in the very early mobilisation group and 208 (20%) of those in the usual care group had a non-fatal serious adverse event, with no reduction in immobility-related complications with very early mobilisation.InterpretationFirst mobilisation took place within 24 h for most patients in this trial. The higher dose, very early mobilisation protocol was associated with a reduction in the odds of a favourable outcome at 3 months. Early mobilisation after stroke is recommended in many clinical practice guidelines worldwide, and our findings should affect clinical practice by refi ning present guidelines; however, clinical recommendations should be informed by future analyses of dose–response associations.